David Maahs

All Publications

• Improving Clinical Outcomes in Newly Diagnosed Pediatric Type 1 Diabetes: Teamwork, Targets, Technology, and Tight Control-The 4T Study. Frontiers in endocrinology Prahalad, P., Zaharieva, D. P., Addala, A., New, C., Scheinker, D., Desai, M., Hood, K. K., Maahs, D. M. 2020; 11: 360

  Abstract

  Many youth with type 1 diabetes (T1D) do not achieve hemoglobin A1c (HbA1c) targets. The mean HbA1c of youth in the USA is higher than much of the developed world. Mean HbA1c in other nations has been successfully modified following benchmarking and quality improvement methods. In this review, we describe the novel 4T approach-teamwork, targets, technology, and tight control-to diabetes management in youth with new-onset T1D. In this program, the diabetes care team (physicians, nurse practitioners, certified diabetes educators, dieticians, social workers, psychologists, and exercise physiologists) work closely to deliver diabetes education from diagnosis. Part of the education curriculum involves early integration of technology, specifically continuous glucose monitoring (CGM), and developing a curriculum around using the CGM to maintain tight control and optimize quality of life.

  View details for DOI 10.3389/fendo.2020.00360

  View details for PubMedID 32733375

  View details for PubMedCentralID PMC7363838

• The Evolution of Hemoglobin A1c Targets for Youth With Type 1 Diabetes: Rationale and Supporting Evidence. Diabetes care Redondo, M. J., Libman, I., Maahs, D. M., Lyons, S. K., Saraco, M., Reusch, J., Rodriguez, H., DiMeglio, L. A. 2021

  Abstract

  The American Diabetes Association 2020 Standards of Medical Care in Diabetes (Standards of Care) recommends a hemoglobin A1c (A1C) of <7% (53 mmol/mol) for many children with type 1 diabetes (T1D), with an emphasis on target personalization. A higher A1C target of <7.5% may be more suitable for youth who cannot articulate symptoms of hypoglycemia or have hypoglycemia unawareness and for those who do not have access to analog insulins or advanced diabetes technologies or who cannot monitor blood glucose regularly. Even less stringent A1C targets (e.g., <8%) may be warranted for children with a history of severe hypoglycemia, severe morbidities, or short life expectancy. During the "honeymoon" period and in situations where lower mean glycemia is achievable without excessive hypoglycemia or reduced quality of life, an A1C <6.5% may be safe and effective. Here, we provide a historical perspective of A1C targets in pediatrics and highlight evidence demonstrating detrimental effects of hyperglycemia in children and adolescents, including increased likelihood of brain structure and neurocognitive abnormalities, microvascular and macrovascular complications, long-term effects, and increased mortality. We also review data supporting a decrease over time in overall severe hypoglycemia risk for youth with T1D, partly associated with the use of newer insulins and devices, and weakened association between lower A1C and severe hypoglycemia risk. We present common barriers to achieving glycemic targets in pediatric diabetes and discuss some strategies to address them. We aim to raise awareness within the community on Standards of Care updates that impact this crucial goal in pediatric diabetes management.

  View details for DOI 10.2337/dc20-1978

  View details for PubMedID 33431422

• Children and youth with diabetes are not at increased risk for hospitalization due to COVID-19. Pediatric diabetes Cardona-Hernandez, R., Cherubini, V., Iafusco, D., Schiaffini, R., Luo, X., Maahs, D. M. 2020

  Abstract

  The severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2), responsible for the coronavirus disease COVID-19, was first identified in Wuhan, China in December 2019. Diabetes, as well as other cardiovascular comorbidities, has been recognized as a major risk factor for outcomes and mortality in adults with COVID19, particularly in the elderly with type 2 diabetes. Based on these conclusions, COVID-19 data on adults have been generalizedto youth with diabetes. Nevertheless, experience from Pediatric Diabetes practices in China (Wuhan), Italy, Spain (Catalonia) and the US (San Francisco Bay Area) consistently report only a single severe case of COVID-19 in a 20-year-old female youth with type 1 diabetes (T1D) that was hospitalized for bilateral pneumonia and was subsequently discharged without complications. In Italy, information on COVID-19 in all children with diabetes is collected on a weekly basis andthose with positive swab test or infection-related symptoms reported to a dedicated national registry. Of a total of 15,500 children tested,11subjects with T1D (age 8-17y) tested positive for COVID-19; 6/11 were asymptomatic and the rest presented with mild symptoms. In the rest of locations, youth with T1D diagnosed with COVID-19 were based on clinical suspicion and a confirmatory PCR test(Wuhan:0; Catalonia-HSJD:3; California-Stanford:2) and all of them were asymptomatic or had a mild course.We suggest that COVID-19 data from adults should not be generalizedto children, adolescents and youth with diabetes as their outcomes and prognosis seem to be similar to their non-diabetic-peers and consistently milder than adults with diabetes. This article is protected by copyright. All rights reserved.

  View details for DOI 10.1111/pedi.13158

  View details for PubMedID 33205546

• Multimethod, multidataset analysis reveals paradoxical relationships between sociodemographic factors, Hispanic ethnicity and diabetes. BMJ open diabetes research & care Knight, G. M., Spencer-Bonilla, G., Maahs, D. M., Blum, M. R., Valencia, A., Zuma, B. Z., Prahalad, P., Sarraju, A., Rodriguez, F., Scheinker, D. 2020; 8 (2)

  Abstract

  INTRODUCTION: Population-level and individual-level analyses have strengths and limitations as do 'blackbox' machine learning (ML) and traditional, interpretable models. Diabetes mellitus (DM) is a leading cause of morbidity and mortality with complex sociodemographic dynamics that have not been analyzed in a way that leverages population-level and individual-level data as well as traditional epidemiological and ML models. We analyzed complementary individual-level and county-level datasets with both regression and ML methods to study the association between sociodemographic factors and DM.RESEARCH DESIGN AND METHODS: County-level DM prevalence, demographics, and socioeconomic status (SES) factors were extracted from the 2018 Robert Wood Johnson Foundation County Health Rankings and merged with US Census data. Analogous individual-level data were extracted from 2007 to 2016 National Health and Nutrition Examination Survey studies and corrected for oversampling with survey weights. We used multivariate linear (logistic) regression and ML regression (classification) models for county (individual) data. Regression and ML models were compared using measures of explained variation (area under the receiver operating characteristic curve (AUC) and R2).RESULTS: Among the 3138 counties assessed, the mean DM prevalence was 11.4% (range: 3.0%-21.1%). Among the 12824 individuals assessed, 1688 met DM criteria (13.2% unweighted; 10.2% weighted). Age, gender, race/ethnicity, income, and education were associated with DM at the county and individual levels. Higher county Hispanic ethnic density was negatively associated with county DM prevalence, while Hispanic ethnicity was positively associated with individual DM. ML outperformed regression in both datasets (mean R2 of 0.679 vs 0.610, respectively (p<0.001) for county-level data; mean AUC of 0.737 vs 0.727 (p<0.0427) for individual-level data).CONCLUSIONS: Hispanic individuals are at higher risk of DM, while counties with larger Hispanic populations have lower DM prevalence. Analyses of population-level and individual-level data with multiple methods may afford more confidence in results and identify areas for further study.

  View details for DOI 10.1136/bmjdrc-2020-001725

  View details for PubMedID 33229378

• Weight Management in Youth with Type 1 Diabetes and Obesity: Challenges and Possible Solutions. Current obesity reports Zaharieva, D. P., Addala, A., Simmons, K. M., Maahs, D. M. 2020

  Abstract

  PURPOSE OF REVIEW: This review highlights challenges associated with weight management in children and adolescents with type 1 diabetes (T1D). Our purpose is to propose potential solutions to improve weight outcomes in youth with T1D.RECENT FINDINGS: A common barrier to weight management in T1D is reluctance to engage in exercise for fear of hypoglycemia. Healthcare practitioners generally provide limited guidance for insulin dosing and carbohydrate modifications to maintain stable glycemia during exercise. Adherence to dietary guidelines is associated with improved glycemia; however, youth struggle to meet recommendations. When psychosocial factors are addressed in combination with glucose trends, this often leads to successful T1D management. Newer medications also hold promise to potentially aid in glycemia and weight management, but further research is necessary. Properly addressing physical activity, nutrition, pharmacotherapy, and psychosocial factors while emphasizing weight management may reduce the likelihood of obesity development and its perpetuation in this population.

  View details for DOI 10.1007/s13679-020-00411-z

  View details for PubMedID 33108635

• A Decade of Disparities in Diabetes Technology Use and HbA1c in Pediatric Type 1 Diabetes: A Transatlantic Comparison. Diabetes care Addala, A., Auzanneau, M., Miller, K., Maier, W., Foster, N., Kapellen, T., Walker, A., Rosenbauer, J., Maahs, D. M., Holl, R. W. 2020

  Abstract

  OBJECTIVE: As diabetes technology use in youth increases worldwide, inequalities in access may exacerbate disparities in hemoglobin A1c (HbA1c). We hypothesized that an increasing gap in diabetes technology use by socioeconomic status (SES) would be associated with increased HbA1c disparities.RESEARCH DESIGN AND METHODS: Participants aged <18 years with diabetes duration ?1 year in the Type 1 Diabetes Exchange (T1DX, U.S., n = 16,457) and Diabetes Prospective Follow-up (DPV, Germany, n = 39,836) registries were categorized into lowest (Q1) to highest (Q5) SES quintiles. Multiple regression analyses compared the relationship of SES quintiles with diabetes technology use and HbA1c from 2010-2012 to 2016-2018.RESULTS: HbA1c was higher in participants with lower SES (in 2010-2012 and 2016-2018, respectively: 8.0% and 7.8% in Q1 and 7.6% and 7.5% in Q5 for DPV; 9.0% and 9.3% in Q1 and 7.8% and 8.0% in Q5 for T1DX). For DPV, the association between SES and HbA1c did not change between the two time periods, whereas for T1DX, disparities in HbA1c by SES increased significantly (P < 0.001). After adjusting for technology use, results for DPV did not change, whereas the increase in T1DX was no longer significant.CONCLUSIONS: Although causal conclusions cannot be drawn, diabetes technology use is lowest and HbA1c is highest in those of the lowest SES quintile in the T1DX, and this difference for HbA1c broadened in the past decade. Associations of SES with technology use and HbA1c were weaker in the DPV registry.

  View details for DOI 10.2337/dc20-0257

  View details for PubMedID 32938745

• COVID-19 and Children With Diabetes-Updates, Unknowns, and Next Steps: First, Do No Extrapolation. Diabetes care DiMeglio, L. A., Albanese-O'Neill, A., Munoz, C. E., Maahs, D. M. 2020

  View details for DOI 10.2337/dci20-0044

  View details for PubMedID 32887703

• A Randomized Trial of Closed-Loop Control in Children with Type 1 Diabetes. The New England journal of medicine Breton, M. D., Kanapka, L. G., Beck, R. W., Ekhlaspour, L., Forlenza, G. P., Cengiz, E., Schoelwer, M., Ruedy, K. J., Jost, E., Carria, L., Emory, E., Hsu, L. J., Oliveri, M., Kollman, C. C., Dokken, B. B., Weinzimer, S. A., DeBoer, M. D., Buckingham, B. A., Chernavvsky, D., Wadwa, R. P., iDCL Trial Research Group, Schoelwer, M., Breton, M., DeBoer, M., Gonder-Frederick, L., Chernavvsky, D., Robic, J., Emory, E., Voelmle, M., Conschafter, K., Morris, K., Barnett, C., Carr, K., Hellmann, J., Kime, M., Oliveri, M., Wadwa, R. P., Forlenza, G., Alonso, G. T., Slover, R., Messer, L., Cobry, E., Jost, E., Berget, C., Towers, L., Lange, S., Buckingham, B., Maahs, D., Lal, R., Ekhlaspour, L., Norlander, L., Hood, K., Town, M., Weir, C., Smith, K., Hsu, L., Shinksy, D., Viana, J., Cengiz, E., Weinzimer, S., Weyman, K., Carria, L., Zgorski, M., Ruedy, K., Beck, R., Borgman, S., Rusnak, J., Kanapka, L., Kollman, C., Murphy, C., Arreza-Rubin, G., Green, N., Kovatchev, B., Brown, S., Anderson, S., Laffel, L., Pinsker, J., Levy, C., Kudva, Y. C., Doyle, F. 3., Renard, E., Cobelli, C., Reznik, Y., Lum, J., Janicek, R., Gabrielson, D. 2020; 383 (9): 836?45

  Abstract

  BACKGROUND: A closed-loop system of insulin delivery (also called an artificial pancreas) may improve glycemic outcomes in children with type 1 diabetes.METHODS: In a 16-week, multicenter, randomized, open-label, parallel-group trial, we assigned, in a 3:1 ratio, children 6 to 13 years of age who had type 1 diabetes to receive treatment with the use of either a closed-loop system of insulin delivery (closed-loop group) or a sensor-augmented insulin pump (control group). The primary outcome was the percentage of time that the glucose level was in the target range of 70 to 180 mg per deciliter, as measured by continuous glucose monitoring.RESULTS: A total of 101 children underwent randomization (78 to the closed-loop group and 23 to the control group); the glycated hemoglobin levels at baseline ranged from 5.7 to 10.1%. The mean (±SD) percentage of time that the glucose level was in the target range of 70 to 180 mg per deciliter increased from 53±17% at baseline to 67±10% (the mean over 16 weeks of treatment) in the closed-loop group and from 51±16% to 55±13% in the control group (mean adjusted difference, 11 percentage points [equivalent to 2.6 hours per day]; 95% confidence interval, 7 to 14; P<0.001). In both groups, the median percentage of time that the glucose level was below 70 mg per deciliter was low (1.6% in the closed-loop group and 1.8% in the control group). In the closed-loop group, the median percentage of time that the system was in the closed-loop mode was 93% (interquartile range, 91 to 95). No episodes of diabetic ketoacidosis or severe hypoglycemia occurred in either group.CONCLUSIONS: In this 16-week trial involving children with type 1 diabetes, the glucose level was in the target range for a greater percentage of time with the use of a closed-loop system than with the use of a sensor-augmented insulin pump. (Funded by Tandem Diabetes Care and the National Institute of Diabetes and Digestive and Kidney Diseases; ClinicalTrials.gov number, NCT03844789.).

  View details for DOI 10.1056/NEJMoa2004736

  View details for PubMedID 32846062

• Characterization of Youth Goal Settingin the Self-Management of Type 1 Diabetes and Associations with HbA1c - The Flexible Lifestyle Empowering Change (FLEX) Trial. Pediatric diabetes Cristello Sarteau, A., Crandell, J., Seid, M., Kichler, J. C., Maahs, D. M., Wang, J., Mayer-Davis, E. 2020

  Abstract

  INTRODUCTION: Youth with type 1 diabetes (T1D) commonly do not meet HbA1c targets. Youth-directed goal setting as a strategy to improve HbA1c has not been well characterized and associations between specific goal focus areas and glycemic control remain unexplored.OBJECTIVE: To inform future trials, this analysis characterized intended focus areas of youth self-directed goals and examinedassociations with change in HbA1c over 18months.METHODS: We inductively coded counseling session data from youth in the Flexible Lifestyle Empowering Change Intervention(n=122, 13-16years, T1D duration >1year, HbA1c 8-13%) to categorize intendedgoalfocus areas and examine associations between frequency of goalfocus areas selected by youth and change in HbA1c between first and last study visit.RESULTS: We identified 13 focus areas that categorized youth goalintentions.Each session where youthgoal setting concurrently incorporatedblood glucose monitoring (BG), CGM, and insulin dosing was associated with a 0.4% (95% CI: -0.77, -0.01; P=0.03) lower HbA1c at the end of intervention participation. No association was observed between HbA1c and frequency of sessions where goalintentionsfocused on BG only (without addressing insulin or CGM) (beta: 0.07; 95% CI: -0.07, 0.21; P=0.33) nor insulin dosing only (without addressing BG or CGM) (beta: 0.00; 95% CI: -0.11, 0.10; P=0.95).CONCLUSIONS: Findings exemplify how guidingyouth goal development and combining multiplebehaviors proximally related to glycemic control into youth goal setting may benefitHbA1c among youth with T1D.More research characterizingoptimal goal setting practicesin youth with T1D is needed. This article is protected by copyright. All rights reserved.

  View details for DOI 10.1111/pedi.13099

  View details for PubMedID 32741045

• 50 Years Ago in TheJournalofPediatrics: Change in Growth Hormone with Obesity: More Consequence Than Cause, Although Questions Remain. The Journal of pediatrics Corcoran, C., Stafford, D. E., Maahs, D. M. 2020; 223: 99

  View details for DOI 10.1016/j.jpeds.2020.02.007

  View details for PubMedID 32711756

• Markers of Cholesterol Synthesis are Elevated in Adolescents and Young Adults with Type 2 Diabetes. Pediatric diabetes Semova, I., Levenson, A. E., Krawczyk, J., Bullock, K., Williams, K. A., Wadwa, R. P., Khoury, P. R., Kimball, T. R., Urbina, E. M., de Ferranti, S. D., Maahs, D. M., Dolan, L. M., Shah, A. S., Clish, C. B., Biddinger, S. B. 2020

  Abstract

  BACKGROUND: Changes in cholesterol absorption and cholesterol synthesis may promote dyslipidemia and cardiovascular disease in individuals with type 2 diabetes mellitus (T2DM).OBJECTIVE: To assess cholesterol synthesis and absorption in lean individuals, obese individuals, and individuals with T2DM.METHODS: We measured lathosterol and lanosterol (markers of cholesterol synthesis) as well as campesterol and beta-sitosterol (markers of cholesterol absorption) in the serum of 15-26years old individuals with T2DM (n=95), as well as their lean (n=98) and obese (n=92) controls.RESULTS: Individuals with T2DM showed a 51% increase in lathosterol and a 65% increase in lanosterol compared to lean controls. Similarly, obese individuals showed a 31% increase in lathosterol compared to lean controls. Lathosterol and lanosterol were positively correlated with body mass index, fasting insulin and glucose, serum triglycerides, and C-reactive protein, and negatively correlated with HDL-cholesterol. In contrast, campesterol and beta-sitosterol were not altered in individuals with T2DM. Moreover, campesterol and beta-sitosterol were negatively correlated with body mass index, fasting insulin, and C-reactive protein and were positively correlated with HDL-cholesterol.CONCLUSIONS: Adolescents and young adults with T2DM show evidence of increased cholesterol synthesis compared to non-diabetic lean controls. These findings suggest that T2DM may promote cardiovascular disease by increasing cholesterol synthesis, and provide additional rationale for the use of cholesterol synthesis inhibitors in this group. This article is protected by copyright. All rights reserved.

  View details for DOI 10.1111/pedi.13097

  View details for PubMedID 32738021

• Type 1 Diabetes Mellitus and the Presence of Other Autoimmune Disease JOURNAL OF PEDIATRICS Seeley, H. H., Maahs, D. M. 2020; 223: 19-+

  View details for Web of Science ID 000551283500006

• Change in Growth Hormone with Obesity: More Consequence Than Cause, Although Questions Remain JOURNAL OF PEDIATRICS Corcoran, C., Stafford, D. J., Maahs, D. M. 2020; 223: 99-+

  View details for Web of Science ID 000551283500021

• 50 Years Ago in TheJournalofPediatrics: Type 1 Diabetes Mellitus and the Presence of Other Autoimmune Disease. The Journal of pediatrics Seeley, H. H., Maahs, D. M. 2020; 223: 19

  View details for DOI 10.1016/j.jpeds.2020.02.009

  View details for PubMedID 32711745

• Uninterrupted Continuous Glucose Monitoring Access is Associated with a Decrease in HbA1c in Youth with Type 1 Diabetes and Public Insurance. Pediatric diabetes Addala, A., Maahs, D. M., Scheinker, D., Chertow, S., Leverenz, B., Prahalad, P. 2020

  Abstract

  OBJECTIVE: Continuous glucose monitor (CGM) use is associated with improved glucose control. We describe the effect of continued and interrupted CGM use on hemoglobin A1c (HbA1c) in youth with public insurance.METHODS: We reviewed 956 visits from 264 youth with type 1 diabetes (T1D) and public insurance. Demographic data, HbA1c and two-week CGM data were collected. Youth were classified as never user, consistent user, insurance discontinuer, and self-discontinuer. Visits were categorized as never-user visit, visit before CGM start, visit after CGM start, visit with continued CGM use, visit with initial loss of CGM, visit with continued loss of CGM, and visit where CGM is regained after loss. Multivariate regression adjusting for age, sex, race, diabetes duration, initial HbA1c, and BMI were used to calculate adjusted mean and delta HbA1c.RESULTS: Adjusted mean HbA1c was lowest for the consistent user group (HbA1c 8.6%;[95%CI 7.9,9.3]). Delta HbA1c (calculated from visit before CGM start) was lower for visit after CGM start (-0.39%;[95%CI -0.78,-0.02]) and visit with continued CGM use (-0.29%;[95%CI -0.61,0.02]) whereas it was higher for visit with initial loss of CGM (0.40%;[95%CI -0.06,0.86]), visit with continued loss of CGM (0.46%;[95%CI 0.06,0.85]), and visit where CGM is regained after loss (0.57%;[95%CI 0.06,1.10]).CONCLUSIONS: Youth with public insurance using CGM have improved HbA1c, but only when CGM use is uninterrupted. Interruptions in use, primarily due to gaps in insurance coverage of CGM, were associated with increased HbA1c. These data support both initial and ongoing coverage of CGM for youth with T1D and public insurance. This article is protected by copyright. All rights reserved.

  View details for DOI 10.1111/pedi.13082

  View details for PubMedID 32681582

• The Neighborhood Deprivation Index and Provider Geocoding Identify Critical Catchment Areas for Diabetes Outreach. The Journal of clinical endocrinology and metabolism Walker, A. F., Hu, H., Cuttriss, N., Anez-Zabala, C., Yabut, K., Haller, M. J., Maahs, D. M. 2020

  Abstract

  PURPOSE: In designing a Project ECHO Type 1 Diabetes (T1D) program in Florida and California, the Neighborhood Deprivation Index (NDI) was used in conjunction with geocoding of primary care providers (PCPs) and endocrinologists in each state to concurrently identify areas with low endocrinology provider density and high health risk/poverty areas. The NDI measures many aspects of poverty proven to be critical indicators of health outcomes.METHODS: The data from the 2013-2017 American Community Survey (ACS) 5-year estimates were used to create NDI maps for California and Florida. In addition, geocoding and 30-minute drive-time buffers were performed using publicly available provider directories for PCPs and endocrinologists in both states by Google Geocoding API and TravelTime Search Application Programming Interface (API).RESULTS: Based on these findings, we defined high need catchment areas as areas with: 1) more than a 30-minute drive to the nearest endocrinologist, but within a 30-minute drive to the nearest PCP; 2) an NDI in the highest quartile; and 3) a population above the median (5,199 for census tracts, and 1,394 for census block groups). Out of the 12,181 census tracts and 34,490 census block groups in California and Florida, we identified 57 tracts and 215 block groups meeting these criteria as high need catchment area.CONCLUSION: Geospatial analysis provides an important initial methodologic step to effectively focus outreach efforts in diabetes program development. The integration of the NDI with geocoded provider directories enables more cost-effective and targeted interventions to reach the most vulnerable populations living with T1D.

  View details for DOI 10.1210/clinem/dgaa462

  View details for PubMedID 32676640

• Clinically Significant Hypoglycemia Is Rare in Youth with T1D during Partial Clinical Remission Addala, A., Gu, A., Zaharieva, D., Prahalad, P., Buckingham, B. A., Scheinker, D., Maahs, D. M. AMER DIABETES ASSOC. 2020

  View details for DOI 10.2337/db20-1294-P

  View details for Web of Science ID 000554509803068

• Advances in Diagnosis and Treatment of Pseudovitamin D Deficiency Rickets JOURNAL OF PEDIATRICS Grover, M., Maahs, D. M. 2020; 221: 200

  View details for Web of Science ID 000536007300037

• The Association between Time-in-Range, Mean Glucose, and Incidence of Hypoglycemia in Youth with Newly Diagnosed T1D Gu, A., Prahalad, P., Maahs, D. M., Addala, A., Scheinker, D. AMER DIABETES ASSOC. 2020

  View details for DOI 10.2337/db20-1289-P

  View details for Web of Science ID 000554509803063

• A Telemedicine-CGM Recommendation System for Personalized Population Health Management Vallon, J., Ward, A. T., Prahalad, P., Hood, K. K., Maahs, D. M., Scheinker, D. AMER DIABETES ASSOC. 2020

  View details for DOI 10.2337/db20-1185-P

  View details for Web of Science ID 000554509802428

• Early Introduction of Continuous Glucose Monitoring Is Well Accepted by Youth and Parents Addala, A., Hanes, S., Zaharieva, D., New, C., Prahalad, P., Maahs, D. M., Hood, K. K., Tanenbaum, M. L. AMER DIABETES ASSOC. 2020

  View details for DOI 10.2337/db20-159-LB

  View details for Web of Science ID 000554509800310

• Newly Diagnosed Pediatric Patients with Type 1 Diabetes Show Steady Decline in Glucose Time-in-Range (TIR) over 1 Year: Pilot Study Zaharieva, D., Prahalad, P., Addala, A., Scheinker, D., Desai, M., Hood, K. K., Leverenz, B., Maahs, D. M. AMER DIABETES ASSOC. 2020

  View details for DOI 10.2337/db20-1295-P

  View details for Web of Science ID 000554509803069

• Early CGM Initiation Improves HbA1c in T1D Youth over the First 15 Months Prahalad, P., Ding, V., Addala, A., New, C., Conrad, B. P., Chmielewski, A., Geels, E., Leverenz, J., Martinez-Singh, A., Sagan, P., Senaldi, J., Freeman, A., Scheinker, D., Hood, K. K., Desai, M., Maahs, D. M. AMER DIABETES ASSOC. 2020

  View details for DOI 10.2337/db20-1297-P

  View details for Web of Science ID 000554509803071

• Enhancing Resources for Healthcare Professionals Caring for People on Intensive Insulin Therapy: Summary from a National Workshop. Diabetes research and clinical practice Levine, B. J., Close, K. L., Dalton, D., Lackner, J. B., Marathe, P. H., McDermott, J. M., Stang, B., TumSuden, K., Yovic, S., Maahs, D. M., Oser, S. M. 2020: 108169

  Abstract

  In June 2019, the Leona M. and Harry B. Helmsley Charitable Trust and JDRF International (JDRF) co-sponsored the Healthcare Professional Resource Workshop in San Francisco, California. The workshop convened stakeholders in the diabetes field in order to: [1] review information and resources created for healthcare professionals (HCPs) caring for people with diabetes on intensive insulin therapy; [2] share knowledge to scale and decentralize diabetes care; [3] identify synergies across the leading diabetes information resources; and [4] determine the areas of unmet need for HCPs caring for people with diabetes on intensive insulin therapy. Here, we summarize the conclusions and recommendations from the workshop.

  View details for DOI 10.1016/j.diabres.2020.108169

  View details for PubMedID 32360398

• International benchmarking in type 1 diabetes: Large difference in childhood HbA1c between 8 high-income countries but similar rise during adolescence-A quality registry study. Pediatric diabetes Anderzen, J., Hermann, J. M., Samuelsson, U., Charalampopoulos, D., Svensson, J., Skrivarhaug, T., Frohlich-Reiterer, E., Maahs, D. M., Akesson, K., Kapellen, T., Fritsch, M., Birkebaek, N. H., Drivvoll, A. K., Miller, K., Stephenson, T., Hofer, S. E., Fredheim, S., Kummernes, S. J., Foster, N., Amin, R., Hilgard, D., Rami-Merhar, B., Dahl-Jorgensen, K., Clements, M., Hanas, R., Holl, R. W., Warner, J. T. 2020

  Abstract

  OBJECTIVES: To identify differences and similarities in HbA1c levels and patterns regarding age and gender in eight high income countries.SUBJECTS: 66071 children and adolescents below18years of age with type 1 diabetes for at least 3months and at least one HbA1c measurement during the study period.METHODS: Pediatric Diabetes Quality Registry data from Austria, Denmark, England, Germany, Norway, Sweden, US and Wales were collected between 2013 and 2014. HbA1c, gender, age and duration were used in the analysis.RESULTS: Distribution of gender and age groups was similar in the eight participating countries. The mean HbA1c varied from 60 to 73mmol/mol (7.6 to 8.8%) between the countries. The increase in HbA1c between the youngest (0-9years) to the oldest (15-17years) age group was close to 8mmol/mol (0.7%) in all countries (P<0.001). Females had a 1mmol/mol (0.1%) higher mean HbA1c than boys (P<0.001) in seven out of eight countries.CONCLUSIONS: In spite of large differences in the mean HbA1c between countries, a remarkable similarity in the increase of HbA1c from childhood to adolescence was found. This article is protected by copyright. All rights reserved.

  View details for DOI 10.1111/pedi.13014

  View details for PubMedID 32249476

• Trust in hybrid closed loop among people with diabetes: Perspectives of experienced system users JOURNAL OF HEALTH PSYCHOLOGY Tanenbaum, M. L., Iturralde, E., Hanes, S. J., Suttiratana, S. C., Ambrosino, J. M., Ly, T. T., Maahs, D. M., Naranjo, D., Walders-Abramson, N., Weinzimer, S. A., Buckingham, B. A., Hood, K. K. 2020; 25 (4): 429?38

  View details for DOI 10.1177/1359105317718615

  View details for Web of Science ID 000523776100001

• The Achilles Reflex Time in Thyroid Disorders JOURNAL OF PEDIATRICS Lee, M., Maahs, D. M. 2020; 217: 78

  View details for Web of Science ID 000508641400051

• Diabetes Technology and Therapy in the Pediatric Age Group. Diabetes technology & therapeutics Maahs, D. M., Shalitin, S. 2020; 22 (S1): S89?S108

  View details for DOI 10.1089/dia.2020.2507

  View details for PubMedID 32069148

• HbA1c Levels in Type 1 Diabetes from Early Childhood to Older Adults: A Deeper Dive into the influence of technology and socio-economic status on HbA1c in the T1D Exchange Clinic Registry Findings. Diabetes technology & therapeutics Miller, K. M., Beck, R. W., Foster, N. C., Maahs, D. M. 2020

  Abstract

  OBJECTIVE: The T1D Exchange Clinic Registry figure of HbA1c levels according to age has become a classic picture of how average HbA1c varies from childhood to elderly. To further assess the course of HbA1c across the life span in T1D, we created similar figures stratified by device use and socio-economic status (SES).METHODS: Mean HbA1c was plotted versus age for 21,253 T1D Exchange Clinic Registry participants with an HbA1c measurement between January 1, 2016 and March 31, 2018 according to device use, race-ethnicity, and measures of SES.RESULTS: Across the age range from childhood to elderly, CGM use without an insulin pump had better average HbA1c than pump without CGM; and among CGM users, pump and injection users had similar HbA1c levels. Any device use (pump or CGM) was associated with better HbA1c levels than no device use across the age range. Lower SES and African American race were associated with higher HbA1c across the age range. Across all device use, SES, and race-ethnicity factors, average HbA1c levels were highest in adolescents and young adults.CONCLUSION: Although the plot of average HbA1c from early childhood to elderly shifts according to device use and SES factors, the shape of the plots remain reasonably constant with highest HbA1c levels in adolescents and young adults. These findings emphasize the importance of targeting adolescence and early adulthood as the ages with the greatest need for improving diabetes management irrespective of device use and SES.

  View details for DOI 10.1089/dia.2019.0393

  View details for PubMedID 31905008

• Longitudinal Changes in Continuous Glucose Monitoring Use Among Individuals With Type 1 Diabetes: International Comparison in the German and Austrian DPV and U.S. T1D Exchange Registries. Diabetes care Miller, K. M., Hermann, J., Foster, N., Hofer, S. E., Rickels, M. R., Danne, T., Clements, M. A., Lilienthal, E., Maahs, D. M., Holl, R. W., T1D Exchange and DPV Registries, Weinstock, R., Izquierdo, R., Sheikh, U., Conboy, P., Bulger, J., Bzdick, S., Klingensmith, G., Banion, C., Barker, J., Cain, C., Nadeau, K., Rewers, M., Rewers, A., Slover, R., Steck, A., Wadwa, P., Zeitler, P., Alonso, G., Forlenza, G., Gerard-Gonzalez, A., Green, M., Gross, S., Majidi, S., Messer, L., Reznick-Lipina, T., Simmons, E., Thivener, K., Weber, I., Willi, S., Lipman, T., Kucheruk, O., Minnock, P., Carchidi, C., Grant, B., Olivos, D., DiMeglio, L., Hannon, T., Evans-Molina, C., Hansen, D., Pottorff, T., Woerner, S., Hildinger, M., Hufferd, R., Newnum, A., Purtlebaugh, D., Smith, L., Wendholt, K., Goland, R., Gandica, R., Williams, K., Pollack, S., Casciano, E., Hochberg, J., Uche, C., Lee, J., Gregg, B., Tan, M., Ang, L., Pop-Busui, R., Thomas, I., Dhadphale, E., Dominowski, J., Garrity, A., Leone, V., Plunkett, C., Plunkett, B., Monzavi, R., Cheung, C., Fisher, L., Kim, M., Miyazaki, B., Pitukcheewanont, P., Sandstrom, A., Austin, J., Change, N., Raymond, J., Ichihara, B., Lipton, M., Flores Garcia, J., Garg, S., Michels, A., Garcetti, R., Green, M., Gutin, R., Nadeau, K., Polsky, S., Shah, V., Voelmle, M., Myers, L., Coe, G., Demmitt, J., Garcia Reyes, Y., Giordano, D., Joshee, P., Nease, E., Nguyen, N., Wolfsdorf, J., Quinn, M., Fontanet, C., Mukherjee, S., Bethin, K., Quattrin, T., Majumdar, I., Mastrandrea, L., Gorman, E., House, A., Michalovic, S., Musial, W., Shine, B., Ahmann, A., Castle, J., Joarder, F., Aby-Daniel, D., Guttmann-Bauman, I., Klopfenstein, B., Morimoto, V., Cady, N., Fitch, R., DeFrang, D., Jahnke, K., Patoine, C., Raman, V., Foster, C., Murray, M., Brown, T., Davis, C., Slater, H., Langvardt, J., Bode, B., Boyd, J., Johnson, J., Newton, C., Ownby, J., Hosey, R., Rastogi, N., Winslett, B., Hirsch, I., DeSantis, A., Failor, R. A., Greenbaum, C., Trence, D., Trikudanathan, S., Khakpour, D., Thomson, P., Sameshima, L., Tordillos, C., Clements, M., Turpin, A., Babar, G., Broussard, J., Cernich, J., Dileepan, K., Feldt, M., Moore, W., Musick, T., Patton, S., Yan, Y., Tsai, S., Bedard, J., Elrod, A., Hester, L., Beidelschies, M., de la Garza, J., Haith, E., James, J., Ramey, E., Slover, J., Valentine, A., Watkins, D., Whisenhunt, M., Wierson, J., Wilson, D., Buckingham, B., Maahs, D., Prahalad, P., Hsu, L., Kingman, R., Tabatabai, I., Liljenquist, D., Sulik, M., Vance, C., Halford, J., Funke, C., Appiagyei-Dankah, Y., Beltz, E., Moran, K., Starkman, H., Cerame, B., Chin, D., Ebner-Lyon, L., Sabanosh, K., Silverman, L., Wagner, C., Cheruvu, S., Fox, M., Melchionne, F., Bergenstal, R., Madden, M., Martens, T., Criego, A., Powers, M., Carlson, A., Beasley, S., Olson, B., Thomas, L., McCann, K., Dunnigan, S., Ashanti, C., Simmons, J., Russell, W., Jaser, S., Kelley, J., Brendle, F., Williams, L., Savin, K., Flowers, K., Williams, G., Hamburger, E., Davis, A., Hammel, B., Cengiz, E., Tamborlane, W., Weyman, K., Van Name, M., Patel, N., Sherr, J., Tichy, E., Steffen, A., Zgorski, M., Carria, L., Finnegan, J., Duran, E., Mehta, S., Katz, M., Laffel, L., Giani, E., Snelgrove, R., Hanono, A., Commissariat, P., Griffith, J., Atkins, A., Harrington, K., Kim, K., Masclans, L., Naik, N., Ambler-Osborn, L., Schultz, A., Cohen, C., Anderson, B., McGill, J., Granados, A., Clifton, M. J., Hurst, S., Kissel, S., Recklein, C., Kruger, D., Bhan, A., Brown, T., Tassopoulos, A., Hailey, A., Remtema, H., Cushman, T., Wintergerst, K., Watson, S., Kingery, S., Rayborn, L., Rush, H., Foster, M., Deuser, A., Rodriguez-Luna, M., Eubanks, S., Rodriguez, H., Bollepalli, S., Smith, L., Shulman, D., Jorgensen, E. V., Eyth, E., Brownstein, R., Rodriguez, J., O'Bria, J., Aleppo-Kacmarek, G., Hahr, A., Molitch, M., Muayed, E., Toft, D., Fulkerson, C., Adelman, D., Massaro, E., Webb, K., Peters, A., Ruelas, V., Harmel, M., Daniels, M., Forghani, N., Flannery, T., Reh, C., Bhangoo, A., Kashmiri, H., Montgomery, K., Trinh, L., Speer, H., Lane, K., Bergenstal, R., Martens, T., Madden, M., Powers, M., Criego, A., Carlson, A., Olson, B., Beasley, S., McCann, K., Thomas, L., Miller, C., Ashanti, C., Solorzano, C. B., Puskaric, J., Benjamin, R., Adkins, D., Spruill, A., Williams, C., Tsalikian, E., Tansey, M., Bansl, N., Cabbage, J., Coffey, J., Schatz, D., Clare-Salzler, M., Cusi, K., Fudge, B., Haller, M., Meehan, C., Rohrs, H., Silverstein, J., Walker, A., Albanese-O'Niell, A., Foss, S., Adams, J., Cintron, M., Thomas, N., Gottschalk, M., Newfield, R., Hashiguchi, M., Sparling, D., Tryggested, J., Beck, J., Less, J., Weber, L., Adi, S., Gitelman, S., Sanda, S., Wong, J., McDonnell, M., Mueller, M., Izadi, Z., Mistry, S., Nelson, B., Looper, L., Frost, C., Redondo, M., Lyons, S., Klinepeter, S., Fegan-Bohm, K., Bacha, F., DeSalvo, D., Butler, A., Hilliard, M., Khetani, F., Yulatic, R., Hudson, R., Irvine, L., Zubair, S., Pace, C., Pitrello, A., Levy, W., Njoku, C., Zipf, W., Dyer, J., Lozano, R., Seiple, D., Corven, G., Jaycox, M., Wood, J., Macleish, S., Gubitosi-Klug, R., Adams, R., McGuigan, P., Casey, T., Campbell, W., Kittelsrud, J., Gupta, A., Peterson, V., Libman, I., Diaz, A., Jelley, D., Crowder, C., Greer, D., Crawford, J., Goudeau, S., Pihoker, C., Yi-Frazier, J., Kearns, S., Pascual, M., Loots, B., Beauregard, N., Rickels, M., O'Brien, S., Agarwal, S., Peleckis, A., Dalton-Bakes, C., Markmann, E., Umpierrez, G., Muir, A., Ramos, C., Behbahani, K., Dhruv, N., Gartzman, N., Nathan, B., Bellin, M., Sunni, M., Flaherty, N., Leschyshyn, J., Schmid, K., Weingartner, D., Ludwig, M., Nelson, B., Kogler, A., Bartyzal, A., Street, A., Pappenfus, B., Sweet, J., Buse, J., Young, L., Bergamo, K., Goley, A., Kirkman, M., Diner, J., Kass, A., Dezube, M., Arnold, K., Evans, T., Sellers, S., Blackman, S., Abel, K., Rasbach, L., Ali, O., Wolfgram, P., Fiallo-Sharer, R., Kramer, J., Beesley, C., Bingham-Tyson, C., Unteutsh, R., Harlan, D., Lee, M., Soyka, L., Feldman, P., Thompson, M., Gallagher-Dorval, K., Hubacz, L., Hartigan, C., Ciccarelli, C., Edelen, R., Edelen, M., Borgwadt, T., Stauffacher, K., DeGrote, K., Gruetzmacher, C., Shepperd, M., Bhargava, A., Wright, D., Fitzgerald, K., Khoo, T., Young, N., Borg, L., Stifel, K., Rail, C., Casas, L., Eidenshink, E., Huber, C., Rieder, A., Tuchscherer, A., Broadbent, M., Dolan, L., Corathers, S., Kichler, J., Sheanon, N., Baugh, H., Standiford, D., Weis, T., Fox, C., Schultz, C., Ritter, A., Vendrame, F., Blashke, C., Matheson, D., Sanders-Branca, N., Rudolph, J., Biersdorf, D., Fitch-Danielson, J., Eckerle-Mize, D., Brendle, F., Fry, J., Davis, D., Lovell, C., Hammel, B., Williams, L., Hoffman, R., Chaudhari, M., Kamboj, M., Carr, L., Casas, L., Blehm, J., Tello, A., Walter, J. A., Ward, R., Broadbent, M., Blomquist, G., Stewart, M., Cross, P., Racki, S., Sterchi, L., Gouine, D., Kiesow, B., Welch, S., Philis-Tsimikas, A., Daily, G., Chang, A., McCallum, J., Garcia, I., Vela, T., Loupasi, I., Rosal, R., Toschi, E., Middelbeek, R., Munshi, M., Slyne, C., Atakov-Castillo, A., Fox, L., Mauras, N., Wasserman, R., Damaso, L., Englert, K., Sikes, K., Ponthieux, K., Phillipson, L., Cohen, A., Gannon, G., Deeb, L., Shiver, A., Schroeder, L., Schworm, W., Graham, K., Levy, C., Lam, D., Burtman, E., Levister, C., Ogyaadu, S., Gassner, H., Duke, J., Touger, L., Newbern, D., Hoekstra, F., Harwood, K., Prasad, V., Daguanno, J., Pratley, R., Corbin, K., Wright, M., Nagel, S., Water, N., Ghere, M., Whitaker, K., Heptulla, R., Katikaneni, R., Johnson-Newell, D., Crandall, J., Powell, D., Anghel, V., Ghanny, S., Aisenberg, J., Chartoff, A., Sivitz, J., Mathus, S., Cospito, T., Thailkill, K., Fowlkes, J., Kalaitzoglou, E., Morales Pozzo, A., Edwards, K. 2020; 43 (1): e1?e2

  View details for DOI 10.2337/dc19-1214

  View details for PubMedID 31672703

• Unintended Consequences of COVID-19: Remember General Pediatrics. The Journal of pediatrics Cherubini, V., Gohil, A., Addala, A., Zanfardino, A., Iafusco, D., Hannon, T., Maahs, D. M. 2020

  View details for DOI 10.1016/j.jpeds.2020.05.004

  View details for PubMedID 32437758

  View details for PubMedCentralID PMC7207102

• A co-formulation of supramolecularly stabilized insulin and pramlintide enhances mealtime glucagon suppression in diabetic pigs. Nature biomedical engineering Maikawa, C. L., Smith, A. A., Zou, L., Roth, G. A., Gale, E. C., Stapleton, L. M., Baker, S. W., Mann, J. L., Yu, A. C., Correa, S., Grosskopf, A. K., Liong, C. S., Meis, C. M., Chan, D., Troxell, M., Maahs, D. M., Buckingham, B. A., Webber, M. J., Appel, E. A. 2020

  Abstract

  Treatment of patients with diabetes with insulin and pramlintide (an amylin analogue) is more effective than treatment with insulin only. However, because mixtures of insulin and pramlintide are unstable and have to be injected separately, amylin analogues are only used by 1.5% of people with diabetes needing rapid-acting insulin. Here, we show that the supramolecular modification of insulin and pramlintide with cucurbit[7]uril-conjugated polyethylene glycol improves the pharmacokinetics of the dual-hormone therapy and enhances postprandial glucagon suppression in diabetic pigs. The co-formulation is stable for over 100?h at 37?°C under continuous agitation, whereas commercial formulations of insulin analogues aggregate after 10?h under similar conditions. In diabetic rats, the administration of the stabilized co-formulation increased the area-of-overlap ratio of the pharmacokinetic curves of pramlintide and insulin from 0.4?±?0.2 to 0.7?±?0.1 (mean?±?s.d.) for the separate administration of the hormones. The co-administration of supramolecularly stabilized insulin and pramlintide better mimics the endogenous kinetics of co-secreted insulin and amylin, and holds promise as a dual-hormone replacement therapy.

  View details for DOI 10.1038/s41551-020-0555-4

  View details for PubMedID 32393892

• Serum Urate Lowering with Allopurinol and Kidney Function in Type 1 Diabetes. The New England journal of medicine Doria, A., Galecki, A. T., Spino, C., Pop-Busui, R., Cherney, D. Z., Lingvay, I., Parsa, A., Rossing, P., Sigal, R. J., Afkarian, M., Aronson, R., Caramori, M. L., Crandall, J. P., de Boer, I. H., Elliott, T. G., Goldfine, A. B., Haw, J. S., Hirsch, I. B., Karger, A. B., Maahs, D. M., McGill, J. B., Molitch, M. E., Perkins, B. A., Polsky, S., Pragnell, M., Robiner, W. N., Rosas, S. E., Senior, P., Tuttle, K. R., Umpierrez, G. E., Wallia, A., Weinstock, R. S., Wu, C., Mauer, M. 2020; 382 (26): 2493?2503

  Abstract

  Higher serum urate levels are associated with an increased risk of diabetic kidney disease. Lowering of the serum urate level with allopurinol may slow the decrease in the glomerular filtration rate (GFR) in persons with type 1 diabetes and early-to-moderate diabetic kidney disease.In a double-blind trial, we randomly assigned participants with type 1 diabetes, a serum urate level of at least 4.5 mg per deciliter, an estimated GFR of 40.0 to 99.9 ml per minute per 1.73 m2 of body-surface area, and evidence of diabetic kidney disease to receive allopurinol or placebo. The primary outcome was the baseline-adjusted GFR, as measured with iohexol, after 3 years plus a 2-month washout period. Secondary outcomes included the decrease in the iohexol-based GFR per year and the urinary albumin excretion rate after washout. Safety was also assessed.A total of 267 patients were assigned to receive allopurinol and 263 to receive placebo. The mean age was 51.1 years, the mean duration of diabetes 34.6 years, and the mean glycated hemoglobin level 8.2%. The mean baseline iohexol-based GFR was 68.7 ml per minute per 1.73 m2 in the allopurinol group and 67.3 ml per minute per 1.73 m2 in the placebo group. During the intervention period, the mean serum urate level decreased from 6.1 to 3.9 mg per deciliter with allopurinol and remained at 6.1 mg per deciliter with placebo. After washout, the between-group difference in the mean iohexol-based GFR was 0.001 ml per minute per 1.73 m2 (95% confidence interval [CI], -1.9 to 1.9; P?=?0.99). The mean decrease in the iohexol-based GFR was -3.0 ml per minute per 1.73 m2 per year with allopurinol and -2.5 ml per minute per 1.73 m2 per year with placebo (between-group difference, -0.6 ml per minute per 1.73 m2 per year; 95% CI, -1.5 to 0.4). The mean urinary albumin excretion rate after washout was 40% (95% CI, 0 to 80) higher with allopurinol than with placebo. The frequency of serious adverse events was similar in the two groups.We found no evidence of clinically meaningful benefits of serum urate reduction with allopurinol on kidney outcomes among patients with type 1 diabetes and early-to-moderate diabetic kidney disease. (Funded by the National Institute of Diabetes and Digestive and Kidney Diseases and others; PERL ClinicalTrials.gov number, NCT02017171.).

  View details for DOI 10.1056/NEJMoa1916624

  View details for PubMedID 32579810

• Sensitive detection of multiple islet autoantibodies in type 1 diabetes using small sample volumes by agglutination-PCR. PloS one Cortez, F. d., Gebhart, D., Robinson, P. V., Seftel, D., Pourmandi, N., Owyoung, J., Bertozzi, C. R., Wilson, D. M., Maahs, D. M., Buckingham, B. A., Mills, J. R., Roforth, M. M., Pittock, S. J., McKeon, A., Page, K., Wolf, W. A., Sanda, S., Speake, C., Greenbaum, C. J., Tsai, C. 2020; 15 (11): e0242049

  Abstract

  Islet autoantibodies are predominantly measured by radioassay to facilitate risk assessment and diagnosis of type 1 diabetes. However, the reliance on radioactive components, large sample volumes and limited throughput renders radioassay testing costly and challenging. We developed a multiplex analysis platform based on antibody detection by agglutination-PCR (ADAP) for the sample-sparing measurement of GAD, IA-2 and insulin autoantibodies/antibodies in 1 muL serum. The assay was developed and validated in 7 distinct cohorts (n = 858) with the majority of the cohorts blinded prior to analysis. Measurements from the ADAP assay were compared to radioassay to determine correlation, concordance, agreement, clinical sensitivity and specificity. The average overall agreement between ADAP and radioassay was above 91%. The average clinical sensitivity and specificity were 96% and 97%. In the IASP 2018 workshop, ADAP achieved the highest sensitivity of all assays tested at 95% specificity (AS95) rating for GAD and IA-2 autoantibodies and top-tier performance for insulin autoantibodies. Furthermore, ADAP correctly identified 95% high-risk individuals with two or more autoantibodies by radioassay amongst 39 relatives of T1D patients tested. In conclusion, the new ADAP assay can reliably detect the three cardinal islet autoantibodies/antibodies in 1muL serum with high sensitivity. This novel assay may improve pediatric testing compliance and facilitate easier community-wide screening for islet autoantibodies.

  View details for DOI 10.1371/journal.pone.0242049

  View details for PubMedID 33186361

• Estimating Dynamic Treatment Regimes in Mobile Health Using V-learning. Journal of the American Statistical Association Luckett, D. J., Laber, E. B., Kahkoska, A. R., Maahs, D. M., Mayer-Davis, E., Kosorok, M. R. 2020; 115 (530): 692?706

  Abstract

  The vision for precision medicine is to use individual patient characteristics to inform a personalized treatment plan that leads to the best possible health-care for each patient. Mobile technologies have an important role to play in this vision as they offer a means to monitor a patient's health status in real-time and subsequently to deliver interventions if, when, and in the dose that they are needed. Dynamic treatment regimes formalize individualized treatment plans as sequences of decision rules, one per stage of clinical intervention, that map current patient information to a recommended treatment. However, most existing methods for estimating optimal dynamic treatment regimes are designed for a small number of fixed decision points occurring on a coarse time-scale. We propose a new reinforcement learning method for estimating an optimal treatment regime that is applicable to data collected using mobile technologies in an out-patient setting. The proposed method accommodates an indefinite time horizon and minute-by-minute decision making that are common in mobile health applications. We show that the proposed estimators are consistent and asymptotically normal under mild conditions. The proposed methods are applied to estimate an optimal dynamic treatment regime for controlling blood glucose levels in patients with type 1 diabetes.

  View details for DOI 10.1080/01621459.2018.1537919

  View details for PubMedID 32952236

  View details for PubMedCentralID PMC7500510

• Dietary intake on days with and without hypoglycemia in youth with type 1 diabetes: The Flexible Lifestyle Empowering Change trial. Pediatric diabetes Igudesman, D., Crandell, J., Zhong, V. W., Cristello Sarteau, A., Kahkoska, A. R., Corbin, K., Pratley, R., Kosorok, M. R., Maahs, D. M., Mayer-Davis, E. J. 2020

  Abstract

  To address a common perception that hypoglycemia is associated with increased dietary intake, we examined calorie and carbohydrate consumption on days with and without hypoglycemia among adolescents with type 1 diabetes (T1D).Days (N=274) with 24-hour dietary recalls and continuous glucose monitoring were available for 122 adolescents with T1D in the Flexible Lifestyle Empowering Change trial (age 13-16?years, diabetes duration >1 year, hemoglobin A1c 8-13%). Days with no hypoglycemia, clinical hypoglycemia (54-69 mg/dL) or clinically serious hypoglycemia (<54 mg/dL) were further split into night- (12-5:59 AM) and day (6 AM-11:59 PM). Mixed models tested whether intake of calories or carbohydrates was greater on days with than without hypoglycemia.Fifty-nine percent, 23% and 18% of days had no hypoglycemia, clinical hypoglycemia and clinically serious hypoglycemia, respectively. Intake of calories and carbohydrates was not statistically significantly different on days with clinical hypoglycemia (57.2 kcal [95% CI -126.7, 241.5]; 12.6 g carbohydrate [95% CI -12.7, 38.0]) or clinically serious hypoglycemia (-74.0 kcal [95% CI -285.9, 137.9]; (-7.8 g carbohydrate [95% CI -36.8, 21.1]), compared to days without hypoglycemia. Differences by day and night were not statistically significant.Among adolescents with T1D, daily intake of calories and carbohydrates did not differ on days with and without hypoglycemia. It is possible that hypoglycemic episodes is caused by undereating relative to insulin dosing, followed by overeating, leading to a net neutral difference. Given the post-hoc nature of these analyses, larger studies should be designed to prospectively test the hypoglycemia-diet relationship. This article is protected by copyright. All rights reserved.

  View details for DOI 10.1111/pedi.13132

  View details for PubMedID 32981192

• Tele-rounds and Case-Based Training: Project ECHO Telementoring Model Applied to Complex Diabetes Care. Pediatric clinics of North America Cuttriss, N., Bouchonville, M. F., Maahs, D. M., Walker, A. F. 2020; 67 (4): 759?72

  Abstract

  Lack of access to subspecialty care and persistent suboptimal outcomes for insulin-requiring patients with diabetes mandates development of innovative health care delivery models. The workforce shortage of endocrinologists in the United States results in primary care providers taking on the role of diabetes specialists despite lack of confidence and knowledge in complex diabetes management. The telementoring model Project ECHO amplifies and democratizes specialty knowledge to reduce disparities in care and improve health outcomes. Project ECHO can be applied to type 1 diabetes and other complex medical conditions to address health disparities and urgent needs of complex patients throughout the lifespan.

  View details for DOI 10.1016/j.pcl.2020.04.017

  View details for PubMedID 32650871

• Glucose Control During Physical Activity and Exercise Using Closed Loop Technology in Adults and Adolescents with Type 1 Diabetes. Canadian journal of diabetes Zaharieva, D. P., Messer, L. H., Paldus, B., O'Neal, D. N., Maahs, D. M., Riddell, M. C. 2020

  Abstract

  Guidelines for safe exercise strategies exist for both pediatric and adult patients living with type 1 diabetes. The management of type 1 diabetes during exercise is complex, but making insulin dosing adjustments in advance of activity can yield positive outcomes and reduce the likelihood of hypoglycemia. Closed loop (also known as automated insulin delivery) systems are able to partially automate insulin delivery and can assist in exercise and overall management of type 1 diabetes. Current exercise guidelines, however, focus primarily on management strategies for patients using multiple daily injections or open loop insulin pump therapy. Closed loop systems require strategic approaches to type 1 diabetes management, including appropriate timing and duration of exercise targets and carbohydrates around exercise that have yet to be standardized. This review aims to showcase how closed loop technology has evolved over the last decade and summarizes a number of closed loop and exercise studies both in free-living conditions and clinical trials. This review also highlights strategies and approaches for exercise and type 1 diabetes management using closed loop systems. Some differences in closed loop strategies for exercise include the importance of pump suspension if disconnecting during exercise, fewer grams of uncovered carbohydrates before exercise and these should be taken close to exercise onset to avoid a rise in automated insulin delivery. A primary goal for future closed loop systems is to detect exercise without user input, so that patients are not required to preset exercise targets well in advance of activity, as are the current recommendations.

  View details for DOI 10.1016/j.jcjd.2020.06.003

  View details for PubMedID 33011134

• Undertreatment of Cardiovascular Risk factors in the Type 1 Diabetes Exchange Clinic Network (USA) and the Prospective Diabetes Follow-up (Germany/Austria) Registries. Diabetes, obesity & metabolism Shah, V. N., Grimsmann, J. M., Foster, N., Dost, A., Miller, K., Pavel, M., Weinstock, R. S., Karges, W., Maahs, D. M., Holl, R. W. 2020

  Abstract

  To examine the control of cardiovascular risk factors in type 1 diabetes (T1D) registries from the USA and Germany/Austria.Data on individuals aged ?12 years with T1D for ?1 year, from the T1D Exchange Clinic Network (T1DX, USA) and the Prospective Diabetes Follow-up Registry (DPV, Germany/Austria) between 1/1/2016 and March 31, 2018 were analyzed. Linear and logistic regression models adjusted for age groups, sex, duration of diabetes, and minority status were used to compare clinical characteristics and achievement of diabetes management targets between registries.The cohort included 47 936 patients (T1DX n = 19 442; DPV n = 28 494). Achievement of A1c goals (<7.0% ages 18-65 years; all others <7.5%) was better in the DPV for those <65 years (all p < 0.001). However, more older adults (age ? 65 years) in the T1DX achieved A1c goal of <7.5% compared to DPV (70% vs 50%, p < 0.001). Frequency of patients with overweight (53% vs 51%, p < 0.001) and obesity (19% vs 9%, p < 0.001) was higher in T1DX. Frequency of meeting blood pressure goals (84% vs 66%, p < 0.001) and lipid goals (73 vs 62%, p < 0.001) was higher in T1DX; this was observed across all age groups (all p < 0.001). Few young adults <26 years received antihypertensive and lipid lowering medications, respectively, despite indications in both registries (T1DX: 5% and 3%, DPV: 3% and 1%).A minority of patients with T1D achieve glycemic targets and the majority are inadequately treated for hypertension and dyslipidemia. This highlights the need for improved diabetes and cardiovascular risk management strategies in T1D. This article is protected by copyright. All rights reserved.

  View details for DOI 10.1111/dom.14069

  View details for PubMedID 32329127

• 50 Years Ago in TheJournalofPediatrics: Advances in Diagnosis and Treatment of Pseudovitamin D Deficiency Rickets. The Journal of pediatrics Grover, M., Maahs, D. M. 2020; 221: 200

  View details for DOI 10.1016/j.jpeds.2019.12.030

  View details for PubMedID 32446481

• Primary Care Providers in California and Florida Report Low Confidence in Providing Type 1 Diabetes Care. Clinical diabetes : a publication of the American Diabetes Association Lal, R. A., Cuttriss, N., Haller, M. J., Yabut, K., Anez-Zabala, C., Hood, K. K., Sheehan, E., Basina, M., Bernier, A., Baer, L. G., Filipp, S. L., Wang, C. J., Town, M. A., Gurka, M. J., Maahs, D. M., Walker, A. F. 2020; 38 (2): 159?65

  Abstract

  People with type 1 diabetes may receive a significant portion of their care from primary care providers (PCPs). To understand the involvement of PCPs in delivering type 1 diabetes care, we performed surveys in California and Florida, two of the most populous and diverse states in the United States. PCPs fill insulin prescriptions but report low confidence in providing type 1 diabetes care and difficulty accessing specialty referrals to endocrinologists.

  View details for DOI 10.2337/cd19-0060

  View details for PubMedID 32327888

  View details for PubMedCentralID PMC7164993

• 50 Years Ago in TheJournal ofPediatrics: The Achilles Reflex Time in Thyroid Disorders. The Journal of pediatrics Lee, M. Y., Maahs, D. M. 2020; 217: 78

  View details for DOI 10.1016/j.jpeds.2019.08.053

  View details for PubMedID 32040414

• THE GUIDED TRANSFER OF CARE IMPROVES ADULT CLINIC SHOW RATE. Endocrine practice : official journal of the American College of Endocrinology and the American Association of Clinical Endocrinologists Lal, R. A., Maahs, D. M., Dosiou, C., Aye, T., Basina, M. 2020

  Abstract

  Objective Every year 500,000 youths in the U.S. with chronic disease turn 18 and eventually require transfer to adult subspecialty care. Evidence-based interventions on the organization of transfer of care are limited, although engagement and retention in adult clinic are considered appropriate outcomes. Sustained continuity of care improves patient satisfaction and reduces hospitalization. Methods We conducted a prospective non-randomized cohort study of patients with pediatric endocrine conditions, age 16-26 years, enrolled upon referral to the adult endocrine clinic of a physician trained in both adult and pediatric endocrinology (Med+Peds Endocrinologist). Patients differed based on whether their referral originated from another pediatric endocrinologist (traditional transfer) or if the Med+Peds Endocrinologist previously saw the patient in his pediatric endocrine clinic (guided transfer). Rather than relying on arbitrary age criteria, guided transfer to adult clinic occurred when physician and patient considered it appropriate. The primary outcome was show rate at the first and second adult visits. Results Of 36 patients, 21 were referred by another pediatric endocrinologist and 15 underwent guided transfer. For traditional transfer, show rate to the first and second visit was 38% compared to 100% in the guided transfer group (p = 0.0001). Subgroup analysis of 27 patients with diabetes revealed that both groups had similar initial HbA1c (p = 0.38) and the guided transfer group maintained HbA1c. Conclusions Most traditional transfers were unsuccessful. Guided transfer was significantly more effective, with every patient successfully transferring, and could be implemented with adult endocrinologists willing to see patients in the pediatric clinic.

  View details for DOI 10.4158/EP-2019-0470

  View details for PubMedID 32045296

• Longitudinal trajectories of BMI z-score: an international comparison of 11,513 Australian, American and German/Austrian/Luxembourgian youth with type 1 diabetes. Pediatric obesity Phelan, H., Foster, N. C., Schwandt, A., Couper, J. J., Willi, S., Kroschwald, P., Jones, T. W., Wu, M., Steigleder-Schweiger, C., Craig, M. E., Maahs, D. M., Prinz, N., Australasian Diabetes Data Network (ADDN) Study Group, t. T. 2019: e12582

  Abstract

  BACKGROUND: BMI fluctuations during puberty are common. Data on individual change in BMI from childhood to young adulthood are limited in youth with type 1 diabetes.OBJECTIVES: To compare longitudinal trajectories of body mass index z score (BMIz) from childhood to adolescence across three registries spanning five countries.METHODS: Data sources: T1DX (USA), DPV (Germany/Austria/Luxembourg) and ADDN (Australia). The analysis included 11,513 youth with type 1 diabetes, duration >1 year, at least one BMI measure at baseline (age 8-10 years) and >5 aggregated BMI measures by year of age during follow-up until age 17 years. BMIz was calculated based on WHO charts. Latent class growth modelling was used to identify subgroups following a similar trajectory of BMIz over time.RESULTS: Five distinct trajectories of BMIz were present in the T1DX and ADDN cohorts, while six trajectories were identified in the DPV cohort. Boys followed more often a low/near-normal pattern while elevated BMIz curves were more likely in girls (ADDN; DPV). For T1DX cohort, no sex differences were observed. Comparing the reference group (BMIz ~0) with the other groups during puberty, higher BMIz was significantly associated with older age at T1D onset, racial/ethnic minority and elevated HbA1c (all p<0.05).CONCLUSION: This multinational study presents unique BMIz trajectories in youth with T1D across three continents. The prevalence of overweight and the longitudinal persistence of overweight support the need for close monitoring of weight and nutrition in this population. The international and individual differences likely result from diverse genetic, environmental and therapeutic factors.

  View details for DOI 10.1111/ijpo.12582

  View details for PubMedID 31691541

• Idiopathic Hypoglycemia: A Study of Twenty-Six Children JOURNAL OF PEDIATRICS Lee, M., Maahs, D. M. 2019; 214: 70

  View details for Web of Science ID 000492192700015

• Type 1 diabetes is associated with an increase in cholesterol absorption markers but a decrease in cholesterol synthesis markers in ayoung adult population. Journal of clinical lipidology Semova, I., Levenson, A. E., Krawczyk, J., Bullock, K., Williams, K. A., Wadwa, R. P., Shah, A. S., Khoury, P. R., Kimball, T. R., Urbina, E. M., de Ferranti, S. D., Bishop, F. K., Maahs, D. M., Dolan, L. M., Clish, C. B., Biddinger, S. B. 2019

  Abstract

  BACKGROUND: To optimize treatment and prevent cardiovascular disease in subjects with type 1 diabetes, it is important to determine how cholesterol metabolism changes with type 1 diabetes.OBJECTIVE: The objective of the study was to compare plasma levels of campesterol and beta-sitosterol, markers of cholesterol absorption, as well as lathosterol, a marker of cholesterol synthesis, in youth with and without type 1 diabetes.METHODS: Serum samples were obtained from adolescent subjects with type 1 diabetes (n=175, mean age 15.2years, mean duration of diabetes 8.2years) and without diabetes (n=74, mean age 15.4years). Campesterol, beta-sitosterol, and lathosterol, were measured using targeted liquid chromatography tandem mass spectrometry, compared between groups, and correlated with the available cardiometabolic variables.RESULTS: Campesterol and beta-sitosterol levels were 30% higher in subjects with type 1 diabetes and positively correlated with hemoglobin A1c levels. In contrast, lathosterol levels were 20% lower in subjects with type 1 diabetes and positively correlated with triglycerides, body mass index, and systolic blood pressure.CONCLUSION: Plasma markers suggest that cholesterol absorption is increased, whereas cholesterol synthesis is decreased in adolescent subjects with type 1 diabetes. Further studies to address the impact of these changes on the relative efficacy of cholesterol absorption and synthesis inhibitors in subjects with type 1 diabetes are urgently needed.

  View details for DOI 10.1016/j.jacl.2019.09.008

  View details for PubMedID 31706902

• Hypoglycemia in children with T1D: Past, Present, and Future Maahs, D. KARGER. 2019: 5

  View details for Web of Science ID 000485922400013

• Closed loop control in adolescents and children during winter sports: Use of the Tandem Control-IQ AP system PEDIATRIC DIABETES Ekhlaspour, L., Forlenza, G. P., Chernavvsky, D., Maahs, D. M., Wadwa, R., Deboer, M. D., Messer, L. H., Town, M., Pinnata, J., Kruse, G., Kovatchev, B. P., Buckingham, B. A., Breton, M. D. 2019; 20 (6): 759?68

  View details for DOI 10.1111/pedi.12867

  View details for Web of Science ID 000478602200012

• Elevated Copeptin, Arterial Stiffness and Elevated Albumin Excretion in Adolescents with Type 1 Diabetes. Pediatric diabetes Wiromrat, P., Bjornstad, P., Vinovskis, C., Chung, L. T., Roncal, C., Pyle, L., Lanaspa, M. A., Johnson, R. J., Cherney, D. Z., Reznick-Lipina, T. K., Bishop, F., Maahs, D. M., Wadwa, R. P. 2019

  Abstract

  OBJECTIVE: We sought to evaluate copeptin concentrations in adolescents with and without type 1 diabetes (T1D) and examine the associations between copeptin and measures of arterial stiffness and kidney dysfunction.RESEARCH DESIGN AND METHODS: This analysis included 169 adolescents with T1D (12-19years of age, 59% girls, mean HbA1c 9.0±1.5% and diabetes duration of 8.6±2.9years), in addition to 61 controls without T1D. Arterial stiffness including carotid-femoral pulse wave velocity (CF-PWV), carotid-radial PWV (CR-PWV), augmentation index normalized to heart rate of 75bpm (AIx@HR75) and brachial artery distensibility (BAD). Serum copeptin, urinary albumin-to-creatinine ratio (UACR) and estimated glomerular filtration rate (eGFR) by serum creatinine and cystatin C were also assessed.RESULTS: Compared to controls, adolescents with T1D had higher median (Q1-Q3) copeptin (7.5 [5.2-11.3] vs. 6.4 [4.8-8.3] pmol/l, p=0.01), mean±SD eGFR (121±23 vs. 112±16 ml/min/1.73m2 , p=0.002) and lower BAD (7.1±1.3 vs. 7.2±1.2%, p=0.02). Adolescents with T1D in the in high tertile copeptin group (>9.1 pmol/l) had higher AIx@HR75 (10.7±1.2 vs. 5±1.2, p=0.001), CR-PWV (5.30±1.0 vs. 5.18±1.0 m/s, p=0.04) and UACR (12±1 vs. 8±1 mg/g, p=0.025) compared to those in low tertile (<5.8 pmol/l) after adjusting for age, sex and eGFR. Copeptin inversely associated with CF-PWV independent of age, sex, eGFR, SBP and HbA1c in T1D adolescents.CONCLUSIONS: Our data demonstrate that elevated copeptin was associated with worse arterial stiffness in adolescents with T1D. These findings suggest that copeptin could improve CVD risk stratification in adolescents with T1D. This article is protected by copyright. All rights reserved.

  View details for DOI 10.1111/pedi.12909

  View details for PubMedID 31433534

• Optimizing Basal Insulin Dosing. The Journal of pediatrics Lal, R. A., Maahs, D. M. 2019

  View details for DOI 10.1016/j.jpeds.2019.07.030

  View details for PubMedID 31383469

• Identification of clinically relevant dysglycemia phenotypes based on continuous glucose monitoring data from youth with type 1 diabetes and elevated hemoglobin A1c PEDIATRIC DIABETES Kahkoska, A. R., Adair, L. A., Aiello, A. E., Burger, K. S., Buse, J. B., Crandell, J., Maahs, D. M., Nguyen, C. T., Kosorok, M. R., Mayer-Davis, E. J. 2019; 20 (5): 556?66

  View details for DOI 10.1111/pedi.12856

  View details for Web of Science ID 000475402500008

• Preventing Early Renal Loss in Diabetes (PERL) Study: A Randomized Double-Blinded Trial of Allopurinol-Rationale, Design, and Baseline Data DIABETES CARE Afkarian, M., Polsky, S., Parsa, A., Aronson, R., Caramori, M., Cherney, D. Z., Crandall, J. P., de Boer, I. H., Elliott, T. G., Galecki, A. T., Goldfine, A. B., Haw, J., Hirsch, I. B., Karger, A. B., Lingvay, I., Maahs, D. M., McGill, J. B., Molitch, M. E., Perkins, B. A., Pop-Busui, R., Pragnell, M., Rosas, S. E., Rossing, P., Senior, P., Sigal, R. J., Spino, C., Tuttle, K. R., Umpierrez, G. E., Wallia, A., Weinstock, R. S., Wu, C., Mauer, M., Doria, A., PERL Study Grp 2019; 42 (8): 1454?63

  Abstract

  Higher serum uric acid (SUA) is associated with diabetic kidney disease (DKD). Preventing Early Renal Loss in Diabetes (PERL) evaluates whether lowering SUA with allopurinol slows glomerular filtration rate (GFR) loss in people with type 1 diabetes (T1D) and mild to moderate DKD. We present the PERL rationale, design, and baseline characteristics.This double-blind, placebo-controlled, multicenter trial randomized 530 participants with T1D, estimated GFR (eGFR) of 40-99.9 mL/min/1.73 m2, SUA ?4.5 m/dL, and micro- to macroalbuminuric DKD or normoalbuminuria with declining kidney function (NDKF) (defined as historical eGFR decline ?3 mL/min/1.73 m2/year) to allopurinol or placebo. The primary outcome is baseline-adjusted iohexol GFR (iGFR) after 3 years of treatment plus a 2-month washout period.Participants are 66% male and 84% white. At baseline, median age was 52 years and diabetes duration was 35 years, 93% of participants had hypertension, and 90% were treated with renin-angiotensin system inhibitors (median blood pressure 127/71 mmHg). Median HbA1c was 8%, SUA 5.9 mg/dL, iGFR 68 mL/min/1.73 m2, and historical eGFR slope -3.5 mL/min/1.73 m2/year. Compared with participants with albuminuria (n = 419), those with NDKF (n = 94) were significantly older (56 vs. 52 years), had lower HbA1c (7.7 vs. 8.1%) and SUA (5.4 vs. 6.0 mg/dL), and had higher eGFR (82 vs. 74 mL/min/1.73 m2) and historical eGFR loss (-4.7 vs. -2.5 mL/min/1.73 m2/year). These differences persisted when comparing groups with similar rates of historical eGFR loss.PERL will determine the effect of allopurinol on mild to moderate DKD in T1D, with or without albuminuria. Participants with normoalbuminuria and rapid GFR loss manifested many DKD risk factors of those with albuminuria, but with less severity.

  View details for DOI 10.2337/dc19-0342

  View details for Web of Science ID 000476786200018

  View details for PubMedID 31186299

  View details for PubMedCentralID PMC6647051

• Burden of Cardiovascular Risk Factors Over Time and Arterial Stiffness in Youth With Type 1 Diabetes Mellitus: The SEARCH for Diabetes in Youth Study JOURNAL OF THE AMERICAN HEART ASSOCIATION Urbina, E. M., Isom, S., Bell, R. A., Bowlby, D. A., D'Agostino, R., Daniels, S. R., Dolan, L. M., Imperatore, G., Marcovina, S. M., Merchant, A. T., Reynolds, K., Shah, A. S., Wadwa, R., Dabelea, D., Lawrence, J. M., Koebnick, C., Reynolds, K., Li, X., Lustigova, E., Holmquist, K., Pettitt, D. J., Dabelea, D., Hamman, R. F., Testaverde, L., Bellatorre, A., Klingensmith, G. J., Rewers, M. J., Maahs, D., Wadwa, P., Daniels, S., Wilkening, G., Kahn, M. G., Bloch, C. A., Powell, J., Love-Osborne, K., Hu, D. C., Dolan, L. M., Standiford, D. A., Mayer-Davis, E. J., Mottl, A., Thomas, J., Turley, C., Liese, A. D., Jackson, M., Knight, L., Bowlby, D., Amrhein, J., Nelson, B., Pihoker, C., Hirsch, I., Liu, L. L., Afkarian, M., Kim, G., Taplin, C., Malik, F., Nip, A., Yi-Frazier, J., Merjaneh, L., Wright, D., Roberts, A., Loots, B., Beauregard, N., Kearns, S., Klingsheim, M., Pascual, M., Franklin, C., Greenbaum, C., Imperatore, G., Saydah, S. H., Linder, B., Gaur, V. P., Strylewicz, G., Chait, A., Harting, J., Wagenknecht, L. E., Divers, J., Reboussin, B., Jensen, E. T., Henkin, L., Goldstein, M. T., Williams, C., Isom, S., Stafford, J., Suerken, C., Pierce, J., SEARCH Diabet Youth Study Grp 2019; 8 (13): e010150

  Abstract

  Background The incidence of type 1 diabetes mellitus (T1DM) in children is increasing, resulting in higher burden of cardiovascular diseases due to diabetes mellitus-related vascular dysfunction. Methods and Results We examined cardiovascular risk factors ( CVRF s) and arterial parameters in 1809 youth with T1DM. Demographics, anthropometrics, blood pressure, and laboratory data were collected at T1DM onset and 5 years later. Pulse wave velocity and augmentation index were collected with tonometry. ANOVA or chi-square tests were used to test for differences in measures of arterial parameters by CVRF . Area under the curve of CVRF s was entered in general linear models to explore determinants of accelerate vascular aging. Participants at the time of arterial measurement were 17.6±4.5 years old, 50% female, 76% non-Hispanic white, and duration of T1DM was 7.8±1.9 years. Glycemic control was poor (glycated hemoglobin, 9.1±1.8%). All arterial parameters were higher in participants with glycated hemoglobin ?9% and pulse wave velocity was higher with lower insulin sensitivity or longer duration of diabetes mellitus. Differences in arterial parameters were found by sex, age, and presence of obesity, hypertension, or dyslipidemia. In multivariable models, higher glycated hemoglobin, lower insulin sensitivity, body mass index, blood pressure, and lipid areas under the curve were associated with accelerated vascular aging. Conclusions In young people with T1DM, persistent poor glycemic control and higher levels of traditional CVRF s are independently associated with arterial aging. Improving glycemic control and interventions to lower CVRF s may prevent future cardiovascular events in young individuals with T1DM.

  View details for DOI 10.1161/JAHA.118.010150

  View details for Web of Science ID 000484578700002

  View details for PubMedID 31213111

  View details for PubMedCentralID PMC6662363

• 670G Clinical Experience Lal, R., Basina, M., Maahs, D. M., Buckingham, B. A., Hood, K. K., Conrad, B. P., Leverenz, J., Chmielewski, A., Peterson, K., Wilson, D. AMER DIABETES ASSOC. 2019

  View details for DOI 10.2337/db19-80-OR

  View details for Web of Science ID 000501366900157

• Personalized Diabetes Management Using Data from Continuous Glucose Monitors Miller, D. R., Ward, A. T., Maahs, D. M., Scheinker, D. AMER DIABETES ASSOC. 2019

  View details for DOI 10.2337/db19-960-P

  View details for Web of Science ID 000501366902323

• The Guided Transition of Care Lal, R., Maahs, D. M., Dosiou, C., Aye, T., Basina, M. AMER DIABETES ASSOC. 2019

  View details for DOI 10.2337/db19-1384-P

  View details for Web of Science ID 000501366903267

• Using Patient Reported Outcomes in Diabetes Research and Practice: Recommendations from a National Workshop. Diabetes research and clinical practice Marrero, D. G., Hilliard, M. E., Maahs, D. M., McAuliffe-Fogarty, A. H., Hunter, C. M. 2019

  Abstract

  The National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) and the American Diabetes Association (ADA) Co-Sponsored the workshop, Using Patient Reported Outcomes in Diabetes Research and Practice. The goal of the workshop was to identify PRO research priorities for those living with type 1 or type 2 diabetes, discuss considerations for use of disease specific versus generic measures, as well as outline research priorities to meet key end-user needs for assessing PROs for diabetes researchers, clinicians/hospital systems, patients/caregivers, and regulators. Here, we summarize the conclusions and recommendations from the workshop.

  View details for DOI 10.1016/j.diabres.2019.05.016

  View details for PubMedID 31128133

• Disordered Eating Behaviors in Youth and Young Adults With Type 1 or Type 2 Diabetes Receiving Insulin Therapy: The SEARCH for Diabetes in Youth Study DIABETES CARE Nip, A. Y., Reboussin, B. A., Dabelea, D., Bellatorre, A., Mayer-Davis, E. J., Kahkoska, A. R., Lawrence, J. M., Peterson, C. M., Dolan, L., Pihoker, C. 2019; 42 (5): 859?66

  Abstract

  This study examines the prevalence of disordered eating behaviors (DEB) and its associations with glycemic control, insulin sensitivity (IS), and psychosocial functioning in a large, diverse cohort of youth and young adults with type 1 or type 2 diabetes.In the SEARCH for Diabetes in Youth study, 2,156 youth and young adults with type 1 diabetes (mean ± SD age 17.7 ± 4.3 years; 50.0% female) and 149 youth and young adults with type 2 diabetes (age 21.8 years ± 3.5; 64.4% female) who were receiving insulin therapy completed the Diabetes Eating Problem Survey-Revised (DEPS-R), a self-reported measure for identifying disordered eating. DEB were defined as a DEPS-R score ?20. Demographic characteristics, clinical measures, and health behaviors of participants with DEB and those without DEB were compared by using t tests.DEB were observed in 21.2% of participants with type 1 diabetes and 50.3% of participants with type 2 diabetes. Participants encountered challenges in maintaining a healthy weight while controlling their diabetes. For both types of diabetes, individuals with DEB had a significantly higher BMI z score, lower insulin sensitivity, more depressive symptoms, and poorer quality of life than those without DEB. Diabetic ketoacidosis episodes occurred more frequently in youth with type 1 diabetes with DEB compared to those without DEB.These findings highlight that DEB are prevalent among youth and young adults with type 1 and type 2 diabetes and who are receiving insulin therapy, and DEB are associated with poorer clinical outcomes and psychosocial well-being. Heightened awareness and early interventions are needed to address DEB for this at-risk population, as are longitudinal studies evaluating the course of DEB and diabetes outcomes.

  View details for DOI 10.2337/dc18-2420

  View details for Web of Science ID 000465238900028

  View details for PubMedID 30862656

  View details for PubMedCentralID PMC6489106

• Estimating Dynamic Treatment Regimes in Mobile Health Using V-Learning JOURNAL OF THE AMERICAN STATISTICAL ASSOCIATION Luckett, D. J., Laber, E. B., Kahkoska, A. R., Maahs, D. M., Mayer-Davis, E., Kosorok, M. R. 2019

  View details for DOI 10.1080/01621459.2018.1537919

  View details for Web of Science ID 000467162700001

• Identification of clinically-relevant dysglycemia phenotypes based on continuous glucose monitoring data from youth with type 1 diabetes and elevated hemoglobin A1c. Pediatric diabetes Kahkoska, A. R., Adair, L. A., Aiello, A. E., Burger, K. S., Buse, J. B., Crandell, J., Maahs, D. M., Nguyen, C. T., Kosorok, M. R., Mayer-Davis, E. J. 2019

  Abstract

  BACKGROUND AND OBJECTIVE: To identify and characterize subgroups of adolescents with type 1 diabetes (T1D) and elevated hemoglobin A1c (HbA1c) who share patterns in their continuous glucose monitoring (CGM) data as 'dysglycemia phenotypes.'METHODS: Data were analyzed from the Flexible Lifestyles Empowering Change randomized trial. Adolescents with T1D (13-16 years, duration>1 year, HbA1c 8-13% (64-119 mmol/mol) wore blinded CGM at baseline for 7-days. Participants were clustered based on eight CGM metrics measuring hypoglycemia, hyperglycemia, and glycemic variability. Clusters were characterized by their baseline features and 18-month changes in HbA1c using adjusted mixed effects models. For comparison, participants were stratified by baseline HbA1c (?/>9.0% (75 mmol/mol)).RESULTS: The study sample included 234 adolescents (49.8% female, age 14.8±1.1, duration 6.4±3.7 years, HbA1c 9.6±1.2% (81±13 mmol/mol). Three Dysglycemia Clusters were identified with significant differences across all CGM metrics (p<0.001). Dysglycemia Cluster 3 (n=40, 17.1%) showed severe hypoglycemia and glycemic variability with moderate hyperglycemia and had a lower baseline HbA1c than Clusters 1 and 2 (p<0.001). This cluster showed increases in HbA1c over 18-mo (p-for-interaction=0.006). No other baseline characteristics were associated with Dysglycemia Clusters. High HbA1c was associated with lower pump use, greater insulin doses, more frequent blood glucose monitoring, lower motivation, and lower adherence to diabetes self-management (all p<0.05).CONCLUSIONS: There are subgroups of adolescents with T1D for which glycemic control is challenged by different aspects of dysglycemia. Enhanced understanding of demographic, behavioral, and clinical characteristics that contribute to CGM-derived dysglycemia phenotypes may reveal strategies to improve treatment. This article is protected by copyright. All rights reserved.

  View details for PubMedID 30972889

• Genetic Determinants of Glycated Hemoglobin in Type 1 Diabetes DIABETES Syreeni, A., Sandholm, N., Cao, J., Toppila, I., Maahs, D. M., Rewers, M. J., Snell-Bergeon, J. K., Costacou, T., Orchard, T. J., Caramori, M., Mauer, M., Klein, B. K., Klein, R., Valo, E., Parkkonen, M., Forsblom, C., Harjutsalo, V., Paterson, A. D., Groop, P., DCCT EDIC Res Grp, FinnDiane Study Grp 2019; 68 (4): 858?67

  View details for DOI 10.2337/db18-0573

  View details for Web of Science ID 000462053100017

• Gluconeogenesis and Insulin in the Ketotic Variety of Childhood Hypoglycemia and in Control Children JOURNAL OF PEDIATRICS Addala, A., Maahs, D. M. 2019; 207: 122

  View details for Web of Science ID 000462161200024

• Cortisol Secretion in Acidotic and Nonacidotic Juvenile Diabetes Mellitus JOURNAL OF PEDIATRICS Cooper, H. C., Maahs, D. M. 2019; 207: 175-+

  View details for Web of Science ID 000462161200033

• Successful At-Home Use of the Tandem Control-IQ Artificial Pancreas System in Young Children During a Randomized Controlled Trial DIABETES TECHNOLOGY & THERAPEUTICS Forlenza, G. P., Ekhlaspour, L., Breton, M., Maahs, D. M., Wadwa, R., DeBoer, M., Messer, L. H., Town, M., Pinnata, J., Kruse, G., Buckingham, B. A., Chernavvsky, D. 2019; 21 (4): 159?69

  View details for DOI 10.1089/dia.2019.0011

  View details for Web of Science ID 000461625400001

• Successful At-Home Use of the Tandem Control-IQ Artificial Pancreas System in Young Children During a Randomized Controlled Trial. Diabetes technology & therapeutics Forlenza, G. P., Ekhlaspour, L., Breton, M., Maahs, D. M., Wadwa, R. P., DeBoer, M., Messer, L. H., Town, M., Pinnata, J., Kruse, G., Buckingham, B. A., Chernavvsky, D. 2019

  Abstract

  OBJECTIVE: Hybrid closed-loop (HCL) artificial pancreas (AP) systems are now moving from research settings to widespread clinical use. In this study, the inControl algorithm developed by TypeZero Technologies was embedded to a commercial Tandem t:slim X2 insulin pump, now called Control-IQ, paired with a Dexcom G6 continuous glucose monitor and tested for superiority against sensor augmented pump (SAP) therapy. Both groups were physician-monitored throughout the clinical trial.RESEARCH DESIGN AND METHODS: In a randomized controlled trial, 24 school-aged children (6-12 years) with type 1 diabetes (T1D) participated in a 3-day home-use trial at two sites: Stanford University and the Barbara Davis Center (50% girls, 9.6±1.9 years of age, 4.5±1.9 years of T1D, baseline hemoglobin A1c 7.35%±0.68%). Study subjects were randomized 1:1 at each site to either HCL AP therapy with the Control-IQ system or SAP therapy with remote monitoring.RESULTS: The primary outcome, time in target range 70-180mg/dL, using Control-IQ significantly improved (71.0%±6.6% vs. 52.8%±13.5%; P=0.001) and mean sensor glucose (153.6±13.5 vs. 180.2±23.1mg/dL; P=0.003) without increasing hypoglycemia time <70mg/dL (1.7% [1.3%-2.1%] vs. 0.9% [0.3%-2.7%]; not significant). The HCL system was active for 94.4% of the study period. Subjects reported that use of the system was associated with less time thinking about diabetes, decreased worry about blood sugars, and decreased burden in managing diabetes.CONCLUSIONS: The use of the Tandem t:slim X2 with Control-IQ HCL AP system significantly improved time in range and mean glycemic control without increasing hypoglycemia in school-aged children with T1D during remote monitored home use.

  View details for PubMedID 30888835

• Identical and Nonidentical Twins: Risk and Factors Involved in Development of Islet Autoimmunity and Type 1 Diabetes DIABETES CARE Triolo, T. M., Fouts, A., Pyle, L., Yu, L., Gottlieb, P. A., Steck, A. K., Greenbaum, C. J., Atkinson, M., Baidal, D., Battaglia, M., Becker, D., Bingley, P., Bosi, E., Buckner, J., Clements, M., Colman, P., DiMeglio, L., Gitelman, S., Goland, R., Gottlieb, P., Goland, R., Gottlieb, P., Herold, K., Knip, M., Krischer, J., Lernmark, A., Moore, W., Moran, A., Muir, A., Palmer, J., Peakman, M., Philipson, L., Raskin, P., Redondo, M., Rodriguez, H., Russell, W., Spain, L., Schatz, D. A., Sosenko, J., Wentworth, J., Wherrett, D., Wilson, D., Winter, W., Ziegler, A., Anderson, M., Antinozzi, P., Benoist, C., Blum, J., Bourcier, K., Chase, P., Clare-Salzler, M., Clynes, R., Eisenbarth, G., Fathman, C. G., Grave, G., Hering, B., Insel, R., Kaufman, F., Kay, T., Leschek, E., Mahon, J., Marks, J. B., Nanto-Salonen, K., Nepom, G., Orban, T., Parkman, R., Pescovitz, M., Peyman, J., Pugliese, A., Roep, B., Roncarolo, M., Savage, P., Simell, O., Sherwin, R., Siegelman, M., Skyler, J. S., Steck, A., Thomas, J., Trucco, M., Wagner, J., Krischer, J. P., Leschek, E., Rafkin, L., Bourcier, K., Cowie, C., Foulkes, M., Insel, R., Krause-Steinrauf, H., Lachin, J. M., Malozowski, S., Peyman, J., Ridge, J., Savage, P., Skyler, J. S., Zafonte, S. J., Rafkin, L., Sosenko, J. M., Kenyon, N. S., Santiago, Krischer, J. 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M., Willi, B., Schwartzman, C., Kapadia, D., Larson, D., McClellan, G., Shaibai, L. A., Kelley, G., Villa, C., Kelley, R., Diamond, M., Kabbani, T., Dajani, F., Hoekstra, M., Magorno, J., Holst, Chauhan, N., Wilson, P., Bononi, M., Sperl, A., Millward, M., Eaton, L., Dean, J., Olshan, H., Renna, C., Milliard, B. L., Bacon, J. B., Quintos, L. S., Topor, S., Bialo, B., Bancroft, A. G., Soto, W., Lagarde, H., Lockemer, T., Vanderploeg, M. A., Ibrahim, M., Huie, Sanchez, R., Edelen, R., Marchiando, J., Palmer, T., Repas, M., Wasson, P., Auker, J., Culbertson, T., Kieffer, D., Voorhees, T., Borgwardt, L., DeRaad, K., Eckert, E., Isaacson, H., Kuhn, A., Carroll, M., Schubert, G., Francis, S., Hagan, T., Le, M., Penn, E., Wickham, C., Leyva, K., Rivera, J., Padilla, Rodriguez, N., Jospe, J., Czyzyk, B., Johnson, U., Nadgir, N., Marlen, G., Prakasam, C., Rieger, N., Glaser, E. C., Heiser, B., Harris, C., Foster, H., Slater, K., Wheeler, D. L., Donaldson, M., Murray, D. E., Hale, R., Tragus, D. R., Word, J., Lynch, L., Pankratz, W., Rogers, R., Newfield, S., Holland, M., Hashiguchi, M., Gottschalk, A., Philis-Tsimikas, R., Rosal, S., Franklin, S. M., Guardado, N., Bohannon, M., Garcia, T., Aguinaldo, J., Phan, Barraza, D., Cohen, J., Pinsker, U., Khan, J., Wiley, L., Jovanovic, P., Misra, M., Wright, D., Cohen, K., Huang, M., Skiles, S., Maxcy, C., Pihoker, K., Cochrane, J., Fosse, S., Kearns, M., Klingsheim, N., Wright, L., Viles, H., Smith, S., Heller, M., Cunningham, A., Daniels, L., Zeiden, J., Field, R., Walker, K. J., Griffin, L., Bartholow, C., Erickson, J., Howard, B., Krabbenhoft, C., Sandman, A., Vanveldhuizen, J., Wurlger, A., Zimmerman, K., Hanisch, L., Davis-Keppen, A., Cotterill, J., Kirby, M., Harris, A., Schmidt, C., Kishiyama, C., Flores, J., Milton, W., Martin, C., Whysham, A., Yerka, T., Freels, J. M., Hassing, J., Webster, R., Green, P., Carter, J., Galloway, D., Hoelzer, S., Roberts, S., Said, P., Sullivan, H. F., Allen, E., Reiter, E., Feinberg, C., Johnson, L. A., Newhook, D., Hagerty, N. H., White, L., Levandoski, J., Kyllo, M., Johnson, C., Benoit, P., Iyer, F., Diamond, H., Hosono, S., Jackman, L., Barette, P., Jones, Sills, S., Bzdick, J., Bulger, R., Weinstock, Douek, R., Andrews, G., Modgill, G., Gyorffy, L., Robin, N., Vaidya, S., Crouch, K., O'Brien, C., Thompson, N., Thorne, J., Blumer, J., Kalic, L., Klepek, J., Paulett, B., Rosolowski, J., Horner, M., Watkins, J. L., Casey, K., Carpenter, C., Burns, J., Horton, C., Pritchard, D., Soetaert, A. G., Wynne, C., Chin, O. Y., Molina, C., Patel, R., Senguttuvan, M., Wheeler, O., Furet, C., Steuhm, D. H., Jelley, S., Goudeau, L., Chalmers, D., Greer, C., Panagiotopoulos, D. L., Metzger, D., Nguyen, M., Horowitz, M. P., Christiansen, E., Glades, C., Morimoto, M., Macarewich, R., Norman, K., Patin, C., Vargas, A., Barbanica, A., Yu, P., Vaidyanathan, W., Osborne, R., Mehra, S., Kaster, S., Neace, J., Horner, G., Reeves, C., Cordrey, L., Marrs, T., Miller, S., Dowshen, D., Doyle, S., Walker, D., Catte, H., Dean, M., Drury-Brown, B., Hackman, M. C., Lee, S., Malkani, K., Cullen, K., Johnson, P., Hampton, M., McCarrell, C., Curtis, E., Paul, Z. Y., Type 1 Diabet TrialNet Study Grp 2019; 42 (2): 192?99

  Abstract

  There are variable reports of risk of concordance for progression to islet autoantibodies and type 1 diabetes in identical twins after one twin is diagnosed. We examined development of positive autoantibodies and type 1 diabetes and the effects of genetic factors and common environment on autoantibody positivity in identical twins, nonidentical twins, and full siblings.Subjects from the TrialNet Pathway to Prevention Study (N = 48,026) were screened from 2004 to 2015 for islet autoantibodies (GAD antibody [GADA], insulinoma-associated antigen 2 [IA-2A], and autoantibodies against insulin [IAA]). Of these subjects, 17,226 (157 identical twins, 283 nonidentical twins, and 16,786 full siblings) were followed for autoantibody positivity or type 1 diabetes for a median of 2.1 years.At screening, identical twins were more likely to have positive GADA, IA-2A, and IAA than nonidentical twins or full siblings (all P < 0.0001). Younger age, male sex, and genetic factors were significant factors for expression of IA-2A, IAA, one or more positive autoantibodies, and two or more positive autoantibodies (all P ? 0.03). Initially autoantibody-positive identical twins had a 69% risk of diabetes by 3 years compared with 1.5% for initially autoantibody-negative identical twins. In nonidentical twins, type 1 diabetes risk by 3 years was 72% for initially multiple autoantibody-positive, 13% for single autoantibody-positive, and 0% for initially autoantibody-negative nonidentical twins. Full siblings had a 3-year type 1 diabetes risk of 47% for multiple autoantibody-positive, 12% for single autoantibody-positive, and 0.5% for initially autoantibody-negative subjects.Risk of type 1 diabetes at 3 years is high for initially multiple and single autoantibody-positive identical twins and multiple autoantibody-positive nonidentical twins. Genetic predisposition, age, and male sex are significant risk factors for development of positive autoantibodies in twins.

  View details for DOI 10.2337/dc18-0288

  View details for Web of Science ID 000457193000013

  View details for PubMedID 30061316

  View details for PubMedCentralID PMC6341285

• Diabetes Technology and Therapy in the Pediatric Age Group. Diabetes technology & therapeutics Maahs, D. M., Lal, R., Shalitin, S. 2019; 21 (S1): S123?S137

  View details for DOI 10.1089/dia.2019.2510

  View details for PubMedID 30785328

• The Effect of Arginine Infusion on Plasma Growth Hormone and Insulin in Children JOURNAL OF PEDIATRICS Zegarra, W., Rosenfeld, R., Maahs, D. M. 2019; 205: 217

  View details for Web of Science ID 000456440200036

• 50 Years Ago in The Journal of Pediatrics: The Effect of Arginine Infusion on Plasma Growth Hormone and Insulin in Children. The Journal of pediatrics Zegarra, W., Rosenfeld, R., Maahs, D. M. 2019; 205: 217

  View details for PubMedID 30684979

• Genetic Determinants of Glycated Hemoglobin in Type 1 Diabetes. Diabetes Syreeni, A., Sandholm, N., Cao, J., Toppila, I., Maahs, D. M., Rewers, M. J., Snell-Bergeon, J. K., Costacou, T., Orchard, T. J., Caramori, M. L., Mauer, M., Klein, B. E., Klein, R., Valo, E., Parkkonen, M., Forsblom, C., Harjutsalo, V., Paterson, A. D., DCCT/EDIC Research Group, Groop, P., FinnDiane Study Group 2019

  Abstract

  Glycated hemoglobin (HbA1c) is an important measure of glycemia in diabetes. HbA1c is influenced by environmental and genetic factors, both in people with and without diabetes. We performed a genome-wide association study (GWAS) for HbA1c in a Finnish type 1 diabetes cohort, FinnDiane. Top results were examined for replication in type 1 diabetes cohorts DCCT/EDIC, WESDR, CACTI, EDC and RASS and a meta-analysis was performed. Three SNPs in high LD on chromosome 13 near relaxin family peptide receptor 2 (RXFP2) were associated with HbA1c in FinnDiane at genome-wide significance (P<5*10-8). The minor alleles of rs2085277 and rs1360072 were associated with higher HbA1c also in the meta-analysis with RASS (P<5*10-8), where these variants had minor allele frequencies ?1%. Furthermore, these SNPs were associated with HbA1c in a non-diabetic East Asian population (P?0.013). A weighted genetic risk score created from 55 HbA1c associated variants from the literature was associated with HbA1c in FinnDiane but explained only a small amount of variation. Understanding the genetic basis of glycemic control and HbA1c may lead to better prevention of diabetic complications.

  View details for PubMedID 30674623

• State of Type 1 Diabetes Management and Outcomes from the T1D Exchange in 2016-2018. Diabetes technology & therapeutics Foster, N. C., Beck, R. W., Miller, K. M., Clements, M. A., Rickels, M. R., DiMeglio, L. A., Maahs, D. M., Tamborlane, W. V., Bergenstal, R., Smith, E., Olson, B. A., Garg, S. K. 2019

  Abstract

  OBJECTIVE: To provide a snapshot of the profile of adults and youth with type 1 diabetes (T1D) in the United States and assessment of longitudinal changes in T1D management and clinical outcomes in the T1D Exchange registry.RESEARCH DESIGN AND METHODS: Data on diabetes management and outcomes from 22,697 registry participants (age 1-93 years) were collected between 2016 and 2018 and compared with data collected in 2010-2012 for 25,529 registry participants.RESULTS: Mean HbA1c in 2016-2018 increased from 65mmol/mol at the age of 5 years to 78mmol/mol between ages 15 and 18, with a decrease to 64mmol/mol by age 28 and 58-63mmol/mol beyond age 30. The American Diabetes Association (ADA) HbA1c goal of <58mmol/mol for youth was achieved by only 17% and the goal of <53mmol/mol for adults by only 21%. Mean HbA1c levels changed little between 2010-2012 and 2016-2018, except in adolescents who had a higher mean HbA1c in 2016-2018. Insulin pump use increased from 57% in 2010-2012 to 63% in 2016-2018. Continuous glucose monitoring (CGM) increased from 7% in 2010-2012 to 30% in 2016-2018, rising >10-fold in children <12 years old. HbA1c levels were lower in CGM users than nonusers. Severe hypoglycemia was most frequent in participants ?50 years old and diabetic ketoacidosis was most common in adolescents and young adults. Racial differences were evident in use of pumps and CGM and HbA1c levels.CONCLUSIONS: Data from the T1D Exchange registry demonstrate that only a minority of adults and youth with T1D in the United States achieve ADA goals for HbA1c.

  View details for PubMedID 30657336

• Hemoglobin A1c Trajectory in Pediatric Patients with Newly Diagnosed Type 1 Diabetes. Diabetes technology & therapeutics Prahalad, P., Yang, J., Scheinker, D., Desai, M., Hood, K., Maahs, D. M. 2019

  Abstract

  Despite advances in diabetes technology and treatment, a majority of children and adolescents with type 1 diabetes (T1D) fail to meet hemoglobin A1c (HbA1c) targets. Among high-income nations, the United States has one of the highest mean HbA1c values. We tracked the HbA1c values of 261 patients diagnosed with T1D in our practice over a 2.5-year period to identify inflection points in the HbA1c trajectory. The HbA1c declined until 5 months postdiagnosis. There was a rise in the HbA1c between the fifth and sixth month postdiagnosis. The HbA1c continued to steadily rise and by 18 months postdiagnosis, the mean HbA1c was 8.2%, which is also our clinic mean. Understanding the HbA1c trajectory early in the course of diabetes has helped to identify opportunities for intensification of diabetes management to flatten the trajectory of HbA1c and improve clinical outcomes.

  View details for DOI 10.1089/dia.2019.0065

  View details for PubMedID 31180244

• Genome-Wide Association Study of Diabetic Kidney Disease Highlights Biology Involved in Glomerular Basement Membrane Collagen. Journal of the American Society of Nephrology : JASN Salem, R. M., Todd, J. N., Sandholm, N., Cole, J. B., Chen, W. M., Andrews, D., Pezzolesi, M. G., McKeigue, P. M., Hiraki, L. T., Qiu, C., Nair, V., Di Liao, C., Cao, J. J., Valo, E., Onengut-Gumuscu, S., Smiles, A. M., McGurnaghan, S. J., Haukka, J. K., Harjutsalo, V., Brennan, E. P., van Zuydam, N., Ahlqvist, E., Doyle, R., Ahluwalia, T. S., Lajer, M., Hughes, M. F., Park, J., Skupien, J., Spiliopoulou, A., Liu, A., Menon, R., Boustany-Kari, C. M., Kang, H. M., Nelson, R. G., Klein, R., Klein, B. E., Lee, K. E., Gao, X., Mauer, M., Maestroni, S., Caramori, M. L., de Boer, I. H., Miller, R. G., Guo, J., Boright, A. P., Tregouet, D., Gyorgy, B., Snell-Bergeon, J. K., Maahs, D. M., Bull, S. B., Canty, A. J., Palmer, C. N., Stechemesser, L., Paulweber, B., Weitgasser, R., Sokolovska, J., Rov?te, V., P?r?gs, V., Prakapiene, E., Radzeviciene, L., Verkauskiene, R., Panduru, N. M., Groop, L. C., McCarthy, M. I., Gu, H. F., Möllsten, A., Falhammar, H., Brismar, K., Martin, F., Rossing, P., Costacou, T., Zerbini, G., Marre, M., Hadjadj, S., McKnight, A. J., Forsblom, C., McKay, G., Godson, C., Maxwell, A. P., Kretzler, M., Susztak, K., Colhoun, H. M., Krolewski, A., Paterson, A. D., Groop, P. H., Rich, S. S., Hirschhorn, J. N., Florez, J. C. 2019

  Abstract

  Although diabetic kidney disease demonstrates both familial clustering and single nucleotide polymorphism heritability, the specific genetic factors influencing risk remain largely unknown.To identify genetic variants predisposing to diabetic kidney disease, we performed genome-wide association study (GWAS) analyses. Through collaboration with the Diabetes Nephropathy Collaborative Research Initiative, we assembled a large collection of type 1 diabetes cohorts with harmonized diabetic kidney disease phenotypes. We used a spectrum of ten diabetic kidney disease definitions based on albuminuria and renal function.Our GWAS meta-analysis included association results for up to 19,406 individuals of European descent with type 1 diabetes. We identified 16 genome-wide significant risk loci. The variant with the strongest association (rs55703767) is a common missense mutation in the collagen type IV alpha 3 chain (COL4A3) gene, which encodes a major structural component of the glomerular basement membrane (GBM). Mutations in COL4A3 are implicated in heritable nephropathies, including the progressive inherited nephropathy Alport syndrome. The rs55703767 minor allele (Asp326Tyr) is protective against several definitions of diabetic kidney disease, including albuminuria and ESKD, and demonstrated a significant association with GBM width; protective allele carriers had thinner GBM before any signs of kidney disease, and its effect was dependent on glycemia. Three other loci are in or near genes with known or suggestive involvement in this condition (BMP7) or renal biology (COLEC11 and DDR1).The 16 diabetic kidney disease-associated loci may provide novel insights into the pathogenesis of this condition and help identify potential biologic targets for prevention and treatment.

  View details for DOI 10.1681/ASN.2019030218

  View details for PubMedID 31537649

• Models, Devices, Properties, and Verification of Artificial Pancreas Systems Kushner, T., Bequette, B., Cameron, F., Forlenza, G., Maahs, D., Sankaranarayanan, S., Lio, P., Zuliani, P. SPRINGER INTERNATIONAL PUBLISHING AG. 2019: 93?131

  View details for DOI 10.1007/978-3-030-17297-8_4

  View details for Web of Science ID 000503198000004

• Five heterogeneous HbA1c trajectories from childhood to adulthood in youth with type 1 diabetes from three different continents - a group-based modeling approach. Pediatric diabetes Clements, M. A., Schwandt, A., Donaghue, K. C., Miller, K., Lück, U., Couper, J. J., Foster, N., Schröder, C., Phelan, H., Maahs, D., Prinz, N., Craig, M. E. 2019

  Abstract

  Only a fraction of youth meet established targets for glycemic control; many experience deteriorating control over time. We compared trajectories of HbA1c among youth from three trans-continental type 1 diabetes (T1D) registries and identified clinical variables associated with the odds of following increasing versus stable trajectories.Analyses included longitudinal data from 15,897 individuals age 8-18 with T1D for at least two years and HbA1c measurements in at least 5?years during the observation period. Cohorts were selected from ADDN (Australia), DPV (Germany/Austria/Luxembourg and the T1DX (US) clinic registries. Group-based trajectory modelling and multivariable logistic regression identified unique HbA1c trajectories and their predictors.5 heterogeneous trajectories of glycemic control in each registry were identified: low, intermediate, high stable; intermediate and high increasing. The overall HbA1c level for each trajectory group tended to be lowest in the DPV, higher in the ADDN, and highest in the T1DX. The absolute level of HbA1c and the proportion of individuals within each trajectory varied across registries: 17-22% of individuals followed an increasing trajectory. Compared with maintaining a stable trajectory, following an increasing trajectory was significantly associated with ethnic minority status, lower height z-score, higher BMI z-score, insulin injection therapy, and the occurrence of severe hypoglycemia; however these factors were not consistent across the three registries.We report the first multinational registry-based comparison of glycemic control trajectories among youth with T1D from three continents and identify possible targets for intervention in those at risk of an increasing HbA1c trajectory. This article is protected by copyright. All rights reserved.

  View details for DOI 10.1111/pedi.12907

  View details for PubMedID 31418521

• The Transatlantic HbA1c gap: differences in glycaemic control across the life-span between the US T1D Exchange and German/Austrian DPV registries. Diabetic medicine : a journal of the British Diabetic Association Hermann, J. M., Miller, K. M., Hofer, S. E., Clements, M. A., Karges, W., Foster, N. C., Fröhlich-Reiterer, E., Rickels, M. R., Rosenbauer, J., DeSalvo, D. J., Holl, R. W., Maahs, D. M. 2019

  Abstract

  To compare HbA1c levels across the lifespan in young people in the USA with those in young people in Germany/Austria, and to examine potential differences in HbA1c levels between sexes, insulin delivery methods and minority status.Data were extracted from the US Type 1 Diabetes Exchange Registry (n=18 381 participants from 73 sites) and from the German/Austrian Prospective Diabetes Follow-up Registry, the DPV (n=32 643 participants from 362 sites). Mean HbA1c was calculated for each year of age for individuals aged ?25 years, and at 2-year age intervals for individuals aged >25 years. Curves for mean HbA1c by age were estimated using locally weighted scatterplot smoothing. HbA1c differences between registries, sexes, insulin delivery methods, and minority status were assessed by age group using multiple linear regression.In both registries, mean HbA1c increased by ~11 mmol/mol (1.0%) between the ages of 9 and 18 years, although at quite different absolute levels: from 66 mmol/mol (8.2%) to 77 mmol/mol (9.2%) in the Type 1 Diabetes Exchange Registry, and from 56 mmol/mol (7.3%) to 66 mmol/mol (8.2%) in the DPV. Sex differences were observed in the DPV only. In the Type 1 Diabetes Exchange Registry, injection users had higher mean HbA1c than pump users across the lifespan, whereas in the DPV higher HbA1c levels in injection users were observed in the age groups 6 to <12 years, 12 to <18 years, and 30 to <50 years (P<0.001). Minority status was significantly associated with higher HbA1c in most age groups in both registries.Significant differences in HbA1c were noted between the USA and Germany/Austria, with disparities more pronounced in early childhood through to young adulthood. Further studies should identify causes for these disparities.

  View details for DOI 10.1111/dme.14148

  View details for PubMedID 31557351

• 50 Years Ago in TheJournal ofPediatrics: Idiopathic Hypoglycemia: A Study of Twenty-Six Children. The Journal of pediatrics Lee, M. Y., Maahs, D. M. 2019; 214: 70

  View details for DOI 10.1016/j.jpeds.2019.06.040

  View details for PubMedID 31655704

• CGM Initiation Soon After Type 1 Diabetes Diagnosis Results in Sustained CGM Use and Wear Time. Diabetes care Prahalad, P., Addala, A., Scheinker, D., Hood, K. K., Maahs, D. M. 2019

  View details for DOI 10.2337/dc19-1205

  View details for PubMedID 31558548

• One Year Clinical Experience of the First Commercial Hybrid Closed-Loop. Diabetes care Lal, R. A., Basina, M., Maahs, D. M., Hood, K., Buckingham, B., Wilson, D. M. 2019

  Abstract

  In September 2016, the U.S. Food and Drug Administration approved the Medtronic 670G "hybrid" closed-loop system. In Auto Mode, this system automatically controls basal insulin delivery based on continuous glucose monitoring data, but requires users enter carbohydrates and blood glucose for boluses. To track real-world experience with this first commercial closed-loop device, we prospectively followed pediatric and adult patients starting the 670G system.This was a 1-year prospective observational study of patients with type 1 diabetes starting the 670G system between May 2017 and May 2018 in clinic.A total of 84 patients received 670G and consented, 5 never returned for follow-up, with 79 (aged 9-61 years) providing data at 1 week and 3, 6, 9, and/or 12 months after Auto Mode initiation. For the 86% (68 out of 79) with 1-week data, 99% (67 out of 68) successfully started. By 3 months, at least 28% (22 out of 79) stopped using Auto Mode; at 6 months, 34% (27 out of 79); at 9 months, 35% (28 out of 79); and by 12 months, 33% (26 out of 79). The primary reason for continuing Auto Mode was desire for increased time in range. Reasons for discontinuation included sensor issues in 62% (16 out of 26), problems obtaining supplies in 12% (3 out of 26), hypoglycemia fear in 12% (3 out of 26), multiple daily injection preference in 8% (2 out of 26), and sports in 8% (2 out of 26). At all visits, there was a significant correlation between hemoglobin A1c (HbA1c) and Auto Mode utilization.While Auto Mode utilization correlates with improved glycemic control, a focus on usability and human factors is necessary to ensure use of Auto Mode. Alarms and sensor calibration are a major patient concern, which future technology should alleviate.

  View details for DOI 10.2337/dc19-0855

  View details for PubMedID 31548247

• Assessment of a Precision Medicine Analysis of a Behavioral Counseling Strategy to Improve Adherence to Diabetes Self-management Among Youth: A Post Hoc Analysis of the FLEX Trial. JAMA network open Kahkoska, A. R., Lawson, M. T., Crandell, J., Driscoll, K. A., Kichler, J. C., Seid, M., Maahs, D. M., Kosorok, M. R., Mayer-Davis, E. J. 2019; 2 (5): e195137

  Abstract

  The Flexible Lifestyles Empowering Change (FLEX) trial, an 18-month randomized clinical trial testing an adaptive behavioral intervention in adolescents with type 1 diabetes, showed no overall treatment effect for its primary outcome, change in hemoglobin A1c (HbA1c) percentage of total hemoglobin, but demonstrated benefit for quality of life (QoL) as a prespecified secondary outcome.To apply a novel statistical method for post hoc analysis that derives an individualized treatment rule (ITR) to identify FLEX participants who may benefit from intervention based on changes in HbA1c percentage (primary outcome), QoL, and body mass index z score (BMIz) (secondary outcomes) during 18 months.This multisite clinical trial enrolled 258 adolescents aged 13 to 16 years with type 1 diabetes for 1 or more years, who had literacy in English, HbA1c percentage of total hemoglobin from 8.0% to 13.0%, a participating caregiver, and no other serious medical conditions. From January 5, 2014, to April 4, 2016, 258 adolescents were recruited. The post hoc analysis excluded adolescents missing outcome measures at 18 months (2 participants [0.8%]) or continuous glucose monitoring data at baseline (40 participants [15.5%]). Data were analyzed from April to December 2018.The FLEX intervention included a behavioral counseling strategy that integrated motivational interviewing and problem-solving skills training to increase adherence to diabetes self-management. The control condition entailed usual diabetes care.Subgroups of FLEX participants were derived from an ITR estimating which participants would benefit from intervention, which would benefit from control conditions, and which would be indifferent. Multiple imputation by chained equations and reinforcement learning trees were used to estimate the ITR. Subgroups based on ITR pertaining to changes during 18 months in 3 univariate outcomes (ie, HbA1c percentage, QoL, and BMIz) and a composite outcome were compared by baseline demographic, clinical, and psychosocial characteristics.Data from 216 adolescents in the FLEX trial were reanalyzed (166 [76.9%] non-Hispanic white; 108 teenaged girls [50.0%]; mean [SD] age, 14.9 [1.1] years; mean [SD] diabetes duration, 6.3 [3.7] years). For the univariate outcomes, a large proportion of FLEX participants had equivalent predicted outcomes under intervention vs usual care settings, regardless of randomization, and were assigned to the muted group (HbA1c: 105 participants [48.6%]; QoL: 63 participants [29.2%]; BMIz: 136 participants [63.0%]). Regarding the BMIz univariate outcome, mean baseline BMIz of participants assigned to the muted group was lower than that of those assigned to the intervention and control groups (muted vs intervention: mean difference, 0.48; 95% CI, 0.21 to 0.75; P?=?.002; muted vs control: mean difference, 0.86; 95% CI, 0.61 to 1.11; P?

  View details for DOI 10.1001/jamanetworkopen.2019.5137

  View details for PubMedID 31150087

• 50 Years Ago in The Journal of Pediatrics: Gluconeogenesis and Insulin in the Ketotic Variety of Childhood Hypoglycemia and in Control Children. The Journal of pediatrics Addala, A., Maahs, D. M. 2019; 207: 122

  View details for PubMedID 30922489

• 50 Years Ago in The Journal of Pediatrics: Cortisol Secretion in Acidotic and Nonacidotic Juvenile Diabetes Mellitus. The Journal of pediatrics Cooper, H. C., Maahs, D. M. 2019; 207: 175

  View details for PubMedID 30922491

• Closed Loop Control in Adolescents and Children During Winter Sports: Use of the Tandem Control-IQ AP System. Pediatric diabetes Ekhlaspour, L., Forlenza, G. P., Chernavvsky, D., Maahs, D. M., Wadwa, R. P., DeBoer, M. D., Messer, L. H., Town, M., Pinnata, J., Kruse, G., Kovatchev, B. P., Buckingham, B. A., Breton, M. D. 2019

  Abstract

  Artificial Pancreas (AP) systems have been shown to improve glycemic control throughout the day and night in adults, adolescents, and children. However, AP testing remains limited during intense and prolonged exercise in adolescents and children. We present the performance of the Tandem Control-IQ AP system in adolescents and children during a winter ski camp study, where high altitude, low temperature, prolonged intense activity, and stress challenged glycemic control.In a randomized controlled trial, 24 adolescents (ages 13-18 years) and 24 school-aged children (6-12 years) with Type 1 Diabetes (T1D) participated in a 48 hr ski camp (?5 h skiing/day) at three sites: Wintergreen, VA; Kirkwood, CA and Breckenridge, CO. Study participants were randomized 1:1 at each site. The control group used remote monitored sensor-augmented pump (RM-SAP), and the experimental group used the t: slim X2 with Control-IQ Technology AP system. All subjects were remotely monitored 24 hours per day by study staff.The Control-IQ system improved percent time within range (70-180 mg/dL) over the entire camp duration: 66.4 ± 16.4vs 53.9 ± 24.8%; P = 0.01 in both children and adolescents. The AP system was associated with a significantly lower average glucose based on CGM data: 161 ± 29.9 vs 176.8 ± 36.5 mg/dL; P = 0.023. There were no differences between groups for hypoglycemia exposure or carbohydrate interventions. There were no adverse events.The use of the Control-IQ AP improved glycemic control and safely reduced exposure to hyperglycemia relative to RM-SAP in pediatric patients with type 1 diabetes during prolonged intensive winter sport activities. This article is protected by copyright. All rights reserved.

  View details for PubMedID 31099946

• Serum uromodulin is associated with urinary albumin excretion in adolescents with type 1 diabetes. Journal of diabetes and its complications Wiromrat, P., Bjornstad, P., Roncal, C., Pyle, L., Johnson, R. J., Cherney, D. Z., Lipina, T., Bishop, F., Maahs, D. M., Wadwa, R. P. 2019

  Abstract

  Early diabetic kidney disease (DKD) occurs in adolescents with type 1 diabetes (T1D). Lower serum uromodulin (SUMOD) predicts DKD progression in adults with T1D. In this study, we demonstrate that lower SUMOD is associated with urinary albumin excretion in adolescents with T1D, suggesting a potential relationship between SUMOD and early kidney dysfunction in T1D youth.

  View details for DOI 10.1016/j.jdiacomp.2019.05.023

  View details for PubMedID 31253490

• Artificial pancreas in pediatrics ARTIFICIAL PANCREAS: CURRENT SITUATION AND FUTURE DIRECTIONS Forlenza, G. P., Messer, L. H., Maahs, D. M., Chernavvsky, D. R., SanchezPena, R. S., Chernavvsky, D. R. 2019: 237?59

  View details for DOI 10.1016/B978-0-12-815655-1.00020-X

  View details for Web of Science ID 000483506400013

• Dysglycemia among youth with type 1 diabetes and suboptimal glycemic control in The Flexible Lifestyle Empowering Change (FLEX) trial. Pediatric diabetes Kahkoska, A. R., Crandell, J., Driscoll, K. A., Kichler, J. C., Seid, M., Mayer-Davis, E. J., Maahs, D. M. 2018

  Abstract

  OBJECTIVE: To examine the prevalence and correlates of non-severe hypoglycemia in adolescents with type 1 diabetes and suboptimal glycemic control, an understudied topic in this group.METHODS: Seven days of blinded continuous glucose monitor data were analyzed in 233 adolescents at baseline of the Flexible Lifestyle Empowering Change (FLEX) trial (13-16 years, type 1 diabetes duration >1 year, and hemoglobin A1c (HbA1c) 8-13% [64-119 mmol]). Incidence of clinical hypoglycemia (54-69 mg/dL) and clinically serious hypoglycemia (<54 mg/dL) was defined as number of episodes ?15 min. Logistic regression modeling determined correlates of long duration of hypoglycemia, categorized by median split among those who experienced hypoglycemia.RESULTS: The sample was 76.1% non-Hispanic white, 49.8% female, age=14.9±1.1 years, diabetes duration=6.4±3.7 years and HbA1c=9.6±1.2% [81±13 mmol/mol]. Over 7-days, 79.4% of youth experienced ?1 hypoglycemic episodes of <70 mg/dL and 55.4% of youth experienced ?1 hypoglycemic episodes of <54 mg/dL. Among all adolescents, the median duration of clinical hypoglycemia and clinically serious hypoglycemia was 21.9 (range 0-250.2) and 4.3 (range 0-209.7) min/day, respectively. Long duration of clinical hypoglycemia (range 1.8-17.4% time overall) and clinically serious hypoglycemia (range 1.2-14.6% time overall) was associated with older age and decreasing HbA1c. Long duration of clinically serious hypoglycemia also was associated with insulin pump use.CONCLUSIONS: Almost 80% of adolescents with elevated HbA1c had an episode of clinical hypoglycemia and >50% had clinically serious hypoglycemia in a week. Increased education alongside access to emerging diabetes technologies may help to prevent hypoglycemia while improving glycemic control. This article is protected by copyright. All rights reserved.

  View details for PubMedID 30536572

• Two-step recruitment process optimizes retention in FLEX clinical trial. Contemporary clinical trials communications Standiford, D. A., Morwessel, N., Bishop, F. K., Thomas, J. M., Smith, E., Crandell, J., Driscoll, K. A., Hunter, C. M., Kichler, J. C., Maahs, D. M., Mayer-Davis, E. J., Seid, M. 2018; 12: 68?75

  Abstract

  Introduction: The Flexible Lifestyle Empowering Change Study (FLEX) is a multi-site randomized controlled trial to test the efficacy of an adaptive behavioral intervention to promote self-management and improve glycemic control for adolescents with type 1 diabetes mellitus. A two-step recruitment process was used to optimize study retention by facilitating informed decision-making regarding participation.Methods: Those who expressed interest at first contact were given more detailed study information followed by telephone calls to the adolescents and their parents to answer questions and explore potential barriers to participation before making a decision regarding study enrollment.Results: Of 694 eligible adolescents who were invited to participate, 397 (57.2%) expressed interest when initially contacted (Step 1). Upon completion of the follow-up telephone calls (Step 2), 276 (39.8%) still agreed to participate; and 258 (37.2%) enrolled and completed a baseline visit with a parent/guardian. Completion rates for measurement visits remained high throughout the study, with an end-of-study retention rate of 93.4%; and only 12 (4.7%) families withdrew from the study.Conclusion: The two-step recruitment process encourages potential participants to thoughtfully evaluate their willingness to participate, as well as their ability to make a commitment to the full completion of study requirements. When demonstrating the efficacy of a randomized controlled trial, it may be preferable to accept lower recruitment rates in order to optimize retention rates. The additional time and effort required to implement this two-step process is worthwhile. With a high retention rate, we can be more confident that the outcomes of the randomized controlled trial actually reflect the impact of the intervention.

  View details for PubMedID 30294698

• Co-occurrence of early diabetes-related complications in adolescents and young adults with type 1 diabetes: an observational cohort study. The Lancet. Child & adolescent health Sauder, K. A., Stafford, J. M., Mayer-Davis, E. J., Jensen, E. T., Saydah, S., Mottl, A., Dolan, L. M., Hamman, R. F., Lawrence, J. M., Pihoker, C., Marcovina, S., D'Agostino, R. B., Dabelea, D., SEARCH for Diabetes in Youth Study Group, Afkarian, M., Amrhein, J., Beauregard, N., Bell, R., Bellatorre, A., Bloch, C. A., Bowlby, D., D'Agostino, R. J., Dabelea, D., Daniels, S., Divers, J., Dolan, L. M., Gaur, V. P., Goldstein, M. T., Greenbaum, C., Hamman, R. F., Harting, J., Henkin, L., Hirsch, I., Holmquist, K., Imperatore, G., Isom, S., Jackson, M., Kahn, M. G., Kearns, S., Kim, G., Klingensmith, G. J., Klingsheim, M., Knight, L., Koebnick, C., Lawrence, J. M., Li, X., Liese, A. D., Linder, B., Liu, L. L., Loots, B., Love-Osborne, K., Maahs, D., Marcovina, S. M., Mayer-Davis, E. J., Merchant, A., Merjaneh, L., Morgan, T., Mottl, A., Nandi-Munshi, D., Neff, J., Nelson, B., Pascual, M., Pettitt, D. J., Pierce, J., Pihoker, C., Powell, J., Reboussin, B., Rewers, M. J., Reynolds, K., Sauder, K. A., Saydah, S. H., Stafford, J., Standiford, D. A., Strylewicz, G., Taplin, C., Testaverde, L., Thomas, J., Wadwa, P., Wagenknecht, L. E., Wilkening, G., Williams, C., Wright, D., Yi-Frazier, J. 2018

  Abstract

  BACKGROUND: One in three adolescents and young adults with type 1 diabetes have at least one early diabetes-related complication or comorbidity. We aimed to examine the prevalence and pattern of co-occurring complications in this population, as well as the related risk factors.METHODS: This observational cohort study includes data from individuals diagnosed with type 1 diabetes before age 20 years who participated in the SEARCH for Diabetes in Youth Study across five sites in the USA. We assessed sociodemographic and metabolic risk factors at baseline and at follow-up, and diabetes complications at follow-up. A frequency analysis was done to examine the difference in observed versus expected prevalence (calculated using a contingency table assuming independence across cells) of co-occurring complications or comorbidities. A cluster analysis was done to identify unique clusters of participants based on demographic characteristics and metabolic risk factors.FINDINGS: 1327 participants who completed the follow-up visit were included in the frequency analysis. The mean age was 10·1 (SD 3·9) years at the time of type 1 diabetes diagnosis and 18·0 (4·1) years at follow-up. At a mean diabetes duration of 7·8 [SD 1·9] years, co-occurrence of any two or more complications was observed in 78 (5·9%) participants, more frequently than expected by chance alone (58 [4·4%], p=0·015). Specifically, the complications that co-occurred more frequently than expected were retinopathy and diabetic kidney disease (11 [0·8%] vs three [0·2%]; p=0·0007), retinopathy and arterial stiffness (13 [1·0%] vs four [0·3%]; p=0·0016), and arterial stiffness and cardiovascular autonomic neuropathy (24 [1·8%] vs 13 [1·0%]; p=0·015). We identified four unique clusters characterised by progressively worsening metabolic risk factor profiles (longer duration of diabetes and higher glycated haemoglobin, non-HDL cholesterol, and waist-to-height ratio). The prevalence of at least two complications increased across the clusters (six [2·3%] of 261 in the low-risk cluster, 32 [6·3%] of 509 in the moderate-risk cluster, 28 [8%] of 348 in the high-risk cluster, and five [20·8%] of 24 in the highest-risk cluster). Compared with the low-risk and moderate-risk clusters, the high-risk and highest-risk clusters were characterised by a lower proportion of participants who were non-Hispanic white, and a higher proportion of participants who had a household income below US$50?000 and did not have private health insurance.INTERPRETATION: Early complications co-occur in adolescents and young adults with type 1 diabetes more frequently than expected. Identification of individuals with adverse risk factors could enable targeted behavioural or medical interventions that reduce the likelihood of early development of lifelong diabetes-related morbidity.FUNDING: US Centers for Disease Control and Prevention, US National Institutes of Health.

  View details for DOI 10.1016/S2352-4642(18)30309-2

  View details for PubMedID 30409691

• Continuous glucose monitoring and glycemic control among youth with type 1 diabetes: International comparison from the T1D Exchange and DPV Initiative PEDIATRIC DIABETES DeSalvo, D. J., Miller, K. M., Hermann, J. M., Maahs, D. M., Hofer, S. E., Clements, M. A., Lilienthal, E., Sherr, J. L., Tauschmann, M., Holl, R. W., T1D Exchange Registry, DPV Registy 2018; 19 (7): 1271?75

  Abstract

  To assess the change in rates of pediatric real-time or intermittent scanning continuous glucose monitoring (CGM) use over the past 5?years, and how it impacts glycemic control, data from two registries were compared: the US-based type 1 diabetes Exchange Registry (T1DX) and the German/Austrian DPV (Prospective Diabetes Follow-Up Registry).Registry participants aged <18 years with T1D duration ?1?year encompassed 29?007 individuals in 2011 and 29?150 participants in 2016. Demographic data, CGM use and hemoglobin A1c (HbA1c) were obtained from medical records.CGM use increased from 2011 to 2016 in both registries across all age groups, regardless of gender, ethnic minority status or insulin delivery method. The increase in CGM use was most pronounced in the youngest patients, and usage rates remain lowest for adolescent patients in 2016. For both registries in 2016, mean HbA1c was lower among CGM users regardless of insulin delivery method compared to pump only (P?

  View details for PubMedID 29923262

  View details for PubMedCentralID PMC6175652

• The early natural history of albuminuria in young adults with youth-onset type 1 and type 2 diabetes. Journal of diabetes and its complications Kahkoska, A. R., Isom, S., Divers, J., Mayer-Davis, E. J., Dolan, L., Shah, A. S., Afkarian, M., Pettitt, D. J., Lawrence, J. M., Marcovina, S., Saydah, S. H., Dabelea, D., Maahs, D. M., Mottl, A. K., SEARCH for Diabetes in Youth Study Group 2018

  Abstract

  AIMS: To determine among adolescents and young adults with youth-onset type 1 diabetes and type 2 diabetes the rates and risk factors for albuminuria regression and progression.METHODS: Data from SEARCH, a longitudinal observational study of youth-onset type 1 diabetes (N?=?1316) and type 2 diabetes (N?=?143) were analyzed. Urine albumin:creatinine ratio (UACR) was measured from random urine specimens at baseline and follow-up visits (mean 7?years later). Albuminuria regression was defined as halving of baseline UACR when baseline UACR was ?30?mug/mg; progression was defined as doubling of baseline UACR when follow-up UACR was ?30?mug/mg, respectively. Multivariable regression assessed risk factors associated with low-risk albuminuria category (combined persistently-low albuminuria and regression) versus moderate-risk albuminuria category (combined persistently-high albuminuria and progression).RESULTS: Albuminuria progression was more common in type 2 diabetes versus type 1 diabetes (15.4% versus 6.0%, p<0.001). Moderate-risk albuminuria was associated with increasing HbA1c (adjusted OR (aOR)?=?1.3, 95% CI 1.1-1.6) and lack of private health insurance (aOR?=?2.7, 95%CI 1.1-6.5) in type 1 diabetes; and African American race (OR?=?4.6, 95% CI 1.2-14.2), lower estimated insulin sensitivity score (aOR?=?2.1, 95% CI 1.4-3.3), baseline UACR (aOR?=?3.2, 95% CI 1.7-5.8), and follow-up estimated glomerular filtration rate (eGFR) (10-unit increase aOR?=?1.3, 95% CI 1.0, 1.5) in type 2 diabetes.CONCLUSIONS: In the first decade of diabetes duration, kidney complications in type 2 diabetes are significantly more aggressive than in type 1 diabetes and may be associated with less modifiable risk factors including race, insulin sensitivity, and eGFR. Early interventions may help reduce long-term kidney complications.

  View details for PubMedID 30316542

• ISPAD Clinical Practice Consensus Guidelines 2018: Diabetes technologies Sherr, J. L., Tauschmann, M., Battelino, T., de Bock, M., Forlenza, G., Roman, R., Hood, K. K., Maahs, D. M. WILEY. 2018: 302?25

  View details for PubMedID 30039513

• Obesity in Type 1 Diabetes: Pathophysiology, Clinical Impact, and Mechanisms ENDOCRINE REVIEWS Corbin, K. D., Driscoll, K. A., Pratley, R. E., Smith, S. R., Maahs, D. M., Mayer-Davis, E. J., Adv Care Type 1 Diabet Obesity 2018; 39 (5): 629?63

  Abstract

  There has been an alarming increase in the prevalence of obesity in people with type 1 diabetes in recent years. Although obesity has long been recognized as a major risk factor for the development of type 2 diabetes and a catalyst for complications, much less is known about the role of obesity in the initiation and pathogenesis of type 1 diabetes. Emerging evidence suggests that obesity contributes to insulin resistance, dyslipidemia, and cardiometabolic complications in type 1 diabetes. Unique therapeutic strategies may be required to address these comorbidities within the context of intensive insulin therapy, which promotes weight gain. There is an urgent need for clinical guidelines for the prevention and management of obesity in type 1 diabetes. The development of these recommendations will require a transdisciplinary research strategy addressing metabolism, molecular mechanisms, lifestyle, neuropsychology, and novel therapeutics. In this review, the prevalence, clinical impact, energy balance physiology, and potential mechanisms of obesity in type 1 diabetes are described, with a special focus on the substantial gaps in knowledge in this field. Our goal is to provide a framework for the evidence base needed to develop type 1 diabetes-specific weight management recommendations that account for the competing outcomes of glycemic control and weight management.

  View details for PubMedID 30060120

• ISPAD Clinical Practice Consensus Guidelines 2018: Glycemic control targets and glucose monitoring for children, adolescents, and young adults with diabetes DiMeglio, L. A., Acerini, C. L., Codner, E., Craig, M. E., Hofer, S. E., Pillay, K., Maahs, D. M. WILEY. 2018: 105?14

  View details for PubMedID 30058221

• ISPAD Clinical Practice Consensus Guidelines 2018: The delivery of ambulatory diabetes care to children and adolescents with diabetes Pihoker, C., Forsander, G., Fantahun, B., Virmani, A., Corathers, S., Benitez-Aguirre, P., Fu, J., Maahs, D. M. WILEY. 2018: 84?104

  View details for PubMedID 30144259

• ISPAD Clinical Practice Consensus Guidelines 2018: Introduction to the Limited Care guidance appendix Codner, E., Acerini, C., Craig, M. E., Hofer, S., Maahs, D. M. WILEY. 2018: 326?27

  View details for PubMedID 30175550

• ISPAD Clinical Practice Consensus Guidelines 2018: What is new in diabetes care? PEDIATRIC DIABETES Codner, E., Acerini, C. L., Craig, M. E., Hofer, S. E., Maahs, D. M. 2018; 19: 5?6

  View details for PubMedID 30276976

• ISPAD Clinical Practice Consensus Guidelines 2018: Assessment and management of hypoglycemia in children and adolescents with diabetes Abraham, M. B., Jones, T. W., Naranjo, D., Karges, B., Oduwole, A., Tauschmann, M., Maahs, D. M. WILEY. 2018: 178?92

  View details for PubMedID 29869358

• Psychosocial and Human Factors During a Trial of a Hybrid Closed Loop System for Type 1 Diabetes Management. Diabetes technology & therapeutics Adams, R. N., Tanenbaum, M. L., Hanes, S. J., Ambrosino, J. M., Ly, T. T., Maahs, D. M., Naranjo, D., Walders-Abramson, N., Weinzimer, S. A., Buckingham, B. A., Hood, K. K. 2018

  Abstract

  BACKGROUND: Hybrid closed loop (HCL) systems are designed to automate insulin delivery to improve type 1 diabetes (T1D) outcomes and reduce user burden and distress. Because the systems only automate some aspects of diabetes care, psychosocial and human factors remain an important consideration in their use. Thus, we examined whether psychosocial and human factors (i.e., distress related to diabetes management, fear of hypoglycemia, and technology attitudes) would (1) change after using the system and (2) predict glycemic outcomes during the trial.SUBJECTS AND METHODS: Fourteen adults and 15 adolescents with T1D participated in a multisite clinical trial of an investigational version of the MiniMed 670G system (Medtronic, Northridge, CA) over 4 to 5 days in a semisupervised outpatient setting. Users completed surveys assessing psychosocial and human factors before beginning the HCL system and at the conclusion of the study. t-Tests and regression analyses were conducted to examine whether these factors changed following trial exposure to the HCL system and predicted glycemic outcomes during the trial.RESULTS: Diabetes management distress decreased and diabetes technology attitudes became more positive over the trial period. Fear of hypoglycemia did not change over the trial period. There was a trend toward greater pretrial management distress predicting less time in range during the trial, controlling for time in range before the trial.CONCLUSIONS: Results suggest that this system is promising for enhancing technology attitudes and reducing management distress. Psychosocial factors, such as management distress, may negatively impact glycemic outcomes and should be a priority area for further investigation.

  View details for PubMedID 30239219

• Psychosocial and Human Factors During a Trial of a Hybrid Closed Loop System for Type 1 Diabetes Management DIABETES TECHNOLOGY & THERAPEUTICS Adams, R. N., Tanenbaum, M. L., Hanes, S. J., Ambrosino, J. M., Ly, T. T., Maahs, D. M., Naranjo, D., Walders-Abramson, N., Weinzimer, S. A., Buckingham, B. A., Hood, K. K. 2018; 20 (10): 648?53

  View details for DOI 10.1089/dia.2018.0174

  View details for Web of Science ID 000445347300001

• Efficacy of the Flexible Lifestyles Empowering Change intervention on metabolic and psychosocial outcomes in adolescents with type 1 diabetes (FLEX): a randomised controlled trial LANCET CHILD & ADOLESCENT HEALTH Mayer-Davis, E. J., Maahs, D. M., Seid, M., Crandell, J., Bishop, F. K., Driscoll, K. A., Hunter, C. M., Kichler, J. C., Standiford, D., Thomas, J. M., FLEX Study Grp 2018; 2 (9): 635?46

  Abstract

  Adolescents with type 1 diabetes commonly have poor glycaemic control. We aimed to test the efficacy of a newly developed adaptive behavioral intervention (Flexible Lifestyles Empowering Change; FLEX) on metabolic and psychosocial outcomes in adolescents with type 1 diabetes.Young people (13-16 years, type 1 diabetes duration >1 year, HbA1c of 64-119 mmol/mol [8·0-13·0%], and without other serious medical conditions or pregnancy) from two clinical sites (Colorado and Ohio, USA) were eligible for enrolment. One caregiver was required to participate actively in the study. Adolescent participants were randomly assigned to the FLEX intervention, which used motivational interviewing and problem-solving skills training to enhance patients' self-management, or usual care control. Intervention fidelity was assessed by a behavioral psychologist with specific expertise in motivational interviewing and who was not otherwise involved in the study via audiotaped sessions. The primary outcome was measurement of glycated haemoglobin A1c (HbA1c) at 18 months. Secondary outcomes included motivation and intention, problem solving skills, self-management behaviors, symptoms of depression, health related quality of life, fear of hypoglycemia, diabetes family conflict, risk factors for T1D complications (BMI, blood pressure, and plasma lipids), and hypoglycemia derived from continuous glucose monitoring (percent time below 3·0 and 3·9 mmol/l [54 and 70 mg/dl]). Intention-to-treat analyses used mixed effects models, with fixed effects including site, timepoint, intervention group, intervention by timepoint, and baseline level of primary (HbA1c) or secondary outcomes (?=0·05). FLEX is registered on clinicaltrials.gov, number NCT01286350.Young people recruited from May 1, 2014 to April 4, 2016 were randomly assigned to FLEX (n=130) or usual care control (n=128). Mean diabetes duration was 6·4 (SD 3·8) years, and 71% (181 out of 256) of patients used insulin pump therapy. Retention was 93%, with 241 out of 258 completing the 18-month assessment. The intervention fidelity score was 4·40 of 5·00 for motivational interviewing and 97% for session content. At 18 months, HbA1c was not significantly different between intervention (83 [13] mmol/mol at baseline; 84 [19] mmol/mol at follow-up); and control (80 [14] mmol/mol at baseline; 82 [17] mmol/mol at follow-up); change in intervention versus control was -0·7 mmol/mol (95% CI -4·7 to 3·4, p=0·75). The intervention was associated with improved scores for motivation (p=0·011), problem solving (p=0·024), diabetes self-management profile (p=0·013), youth report of overall quality of life (p=0·0089), selected domains related to fear of hypoglycaemia (p=0·036 for youth's helplessness or worry; p=0·0051 for parent's efforts to maintain high blood glucose), parent report of diabetes family conflict (p=0·0001), total cholesterol (p=0·038), and diastolic blood pressure (p=0·015). A total of 54 serious adverse events were identified; 34 of these were diabetes-related, including low blood glucose requiring assistance (n=3) and high blood glucose with diabetic ketoacidosis and emergency response (n=25).The FLEX intervention did not significantly change HbA1c among these adolescents with elevated HbA1c, but did positively affect several psychosocial outcomes over 18 months. Further analyses will provide information regarding drivers of positive response to the intervention and will point to future directions for improvement in the approach.National Institutes of Health and National Institute of Diabetes Digestive Diseases and Kidney and the Helmsley Charitable Trust.

  View details for PubMedID 30119757

• Type 1 Diabetes in Children and Adolescents: A Position Statement by the American Diabetes Association DIABETES CARE Chiang, J. L., Maahs, D. M., Garvey, K. C., Hood, K. K., Laffel, L. M., Weinzimer, S. A., Wolfsdorf, J. I., Schatz, D. 2018; 41 (9): 2026?44

  View details for PubMedID 30093549

  View details for PubMedCentralID PMC6105320

• Age at type 1 diabetes onset: a new risk factor and call for focused treatment LANCET Basina, M., Maahs, D. M. 2018; 392 (10146): 453?54

  View details for DOI 10.1016/S0140-6736(18)31811-7

  View details for Web of Science ID 000441292200004

• Sustained Continuous Glucose Monitor Use in Low-Income Youth with Type 1 Diabetes Following Insurance Coverage Supports Expansion of Continuous Glucose Monitor Coverage for All. Diabetes technology & therapeutics Prahalad, P., Addala, A., Buckingham, B., Wilson, D. M., Maahs, D. M. 2018

  View details for PubMedID 30020810

• Sustained Continuous Glucose Monitor Use in Low-Income Youth with Type 1 Diabetes Following Insurance Coverage Supports Expansion of Continuous Glucose Monitor Coverage for All DIABETES TECHNOLOGY & THERAPEUTICS Prahalad, P., Addala, A., Buckingham, B., Wilson, D. M., Maahs, D. M. 2018; 20 (9): 632?34

  View details for DOI 10.1089/dia.2018.0204

  View details for Web of Science ID 000439550100001

• Can Real World Evidence on Body Mass Index Trajectories Inform Clinical Practice? The Journal of pediatrics Addala, A., Maahs, D. M. 2018

  View details for PubMedID 30025670

• Type 2 diabetes mellitus (T2DM) in youth. Pediatric diabetes Zeitler, P., Arslanian, S., Fu, J., Pinhas-Hamiel, O., Reinehr, T., Tandon, N., Urakami, T., Wong, J., Maahs, D. M. 2018

  Abstract

  The 2018 ISPAD Guidelines have been updated based on published data and evolving expert opinion since the 2014 chapter was published, including treatment target (HbA1c=7%) and intensification of management recommendations. This article is protected by copyright. All rights reserved.

  View details for PubMedID 29999228

• Diabetes Technology Use Among Pregnant and Nonpregnant Women with T1D in the T1D Exchange. Diabetes technology & therapeutics Polsky, S., Wu, M., Bode, B. W., DuBose, S. N., Goland, R. S., Maahs, D. M., Foster, N. C., Peters, A. L., Levy, C. J., Shah, V. N., Beck, R. W. 2018

  Abstract

  BACKGROUND: Gestational tight glycemic control is critical for women with type 1 diabetes (T1D). Limited data exist on the adoption and retention of diabetes technologies among women in different parity strata.METHODS: We compared T1D management between T1D Exchange clinic registry participants (mean age 28±9 years, 84% white non-Hispanic, and median T1D duration 13 years) who were pregnant at enrollment or year 1 follow-up ("recently pregnant" between 2010 and 2013, n=214), ever (but not recently) pregnant (n=1540), and never pregnant (n=2586). We examined self-reported maternal and fetal outcomes in 130 women who delivered a baby within the last year.RESULTS: Recently pregnant women had the lowest hemoglobin A1c (6.5% pregnant vs. 7.8% ever pregnant vs. 8.0% never pregnant, P<0.001). Recently pregnant women reported the highest use of continuous subcutaneous insulin infusion (74% vs. 60% vs. 58%, adjusted P<0.001) and continuous glucose monitor (CGM) (36% vs.17% vs. 12%, adjusted P<0.001) therapies compared with ever or never pregnant women, respectively, after adjusting for age, diabetes duration, and socioeconomic status. Among women 18-25 years old, CGM use was highest among recently pregnant women (adjusted P=0.0022). Never pregnant women 26-45 years old had a higher use of CGM compared with younger counterparts (adjusted P<0.001). Adverse maternal and fetal outcomes were common.CONCLUSIONS: Despite high uptake levels of advanced diabetes technologies among pregnant women, rates of adverse maternal and fetal outcomes remain high. More studies are needed to determine how these technologies could be best used in pregnancy and postpartum to improve health outcomes among women with T1D.

  View details for PubMedID 29990438

• Diabetes Technology Use Among Pregnant and Nonpregnant Women with T1D in the T1D Exchange DIABETES TECHNOLOGY & THERAPEUTICS Polsky, S., Wu, M., Bode, B. W., DuBose, S. N., Goland, R. S., Maahs, D. M., Foster, N. C., Peters, A. L., Levy, C. J., Shah, V. N., Beck, R. W., T1D Exchange Clinic Network 2018; 20 (8): 517?23

  View details for DOI 10.1089/dia.2018.0033

  View details for Web of Science ID 000438203900001

• Eating patterns and food intake of persons with type 1 diabetes within the T1D exchange DIABETES RESEARCH AND CLINICAL PRACTICE Powers, M. A., Gal, R. L., Connor, C. G., Mangan, M., Maahs, D. M., Clements, M. A., Mayer-Davis, E. J. 2018; 141: 217?28

  Abstract

  To identify dietary intake and eating patterns of people with type 1 diabetes from childhood to later adulthood in relation to HbA1c.Trained interviewers conducted 24-hour recalls via phone utilizing a multiple pass approach and administered two nutrition questionnaires; 463 participants (or parents of participants) within the T1D Exchange clinic registry were included. Participants were 5 to 81?years with 80-101 participants in five age groups; 56% were female, and 92% were white, with a median diabetes duration of 11.1?years and a median HbA1c of 7.4% [57?mmol/mol]).Those with type 1 diabetes consumed less calories from carbohydrates and more from fats and protein than those in the general population, based on the National Health and Nutrition Examination Survey data. Carbohydrate intake was not correlated with HbA1c levels. Increased fiber intake, more eating occasions, higher Healthy Eating Index scores, and higher nutrition knowledge scores were each associated with lower HbA1c levels.Food intake, eating patterns and nutrition knowledge are associated with glycemic control across a registry-based cohort of adults and children with type 1 diabetes. Additionally, these data can inform the design of future studies to advance our understanding of nutritional influences on type 1 diabetes self-care and control.

  View details for PubMedID 29772288

• Advances in Care for Insulin-Requiring Patients Without Closed Loop. Diabetes technology & therapeutics Lal, R. A., Buckingham, B., Maahs, D. M. 2018; 20 (S2): S285?S291

  View details for PubMedID 29916743

• Exploring Variation in Glycemic Control Across and Within Eight High-Income Countries: A Cross-sectional Analysis of 64,666 Children and Adolescents With Type 1 Diabetes DIABETES CARE Charalampopoulos, D., Hermann, J. M., Svensson, J., Skrivarhaug, T., Maahs, D. M., Akesson, K., Warner, J. T., Holl, R. W., Birkebaek, N. H., Drivvoll, A. K., Miller, K. M., Svensson, A., Stephenson, T., Hofer, S. E., Fredheim, S., Kummernes, S. J., Foster, N., Hanberger, L., Amin, R., Rami-Merhar, B., Johansen, A., Dahl-Jorgensen, K., Clements, M., Hanas, R. 2018; 41 (6): 1180?87

  Abstract

  International studies on childhood type 1 diabetes (T1D) have focused on whole-country mean HbA1c levels, thereby concealing potential variations within countries. We aimed to explore the variations in HbA1c across and within eight high-income countries to best inform international benchmarking and policy recommendations.Data were collected between 2013 and 2014 from 64,666 children with T1D who were <18 years of age across 528 centers in Germany, Austria, England, Wales, U.S., Sweden, Denmark, and Norway. We used fixed- and random-effects models adjusted for age, sex, diabetes duration, and minority status to describe differences between center means and to calculate the proportion of total variation in HbA1c levels that is attributable to between-center differences (intraclass correlation [ICC]). We also explored the association between within-center variation and children's glycemic control.Sweden had the lowest mean HbA1c (59 mmol/mol [7.6%]) and together with Norway and Denmark showed the lowest between-center variations (ICC ?4%). Germany and Austria had the next lowest mean HbA1c (61-62 mmol/mol [7.7-7.8%]) but showed the largest center variations (ICC ?15%). Centers in England, Wales, and the U.S. showed low-to-moderate variation around high mean values. In pooled analysis, differences between counties remained significant after adjustment for children characteristics and center effects (P value <0.001). Across all countries, children attending centers with more variable glycemic results had higher HbA1c levels (5.6 mmol/mol [0.5%] per 5 mmol/mol [0.5%] increase in center SD of HbA1c values of all children attending a specific center).At similar average levels of HbA1c, countries display different levels of center variation. The distribution of glycemic achievement within countries should be considered in developing informed policies that drive quality improvement.

  View details for PubMedID 29650804

  View details for PubMedCentralID PMC5961394

• Guidelines to Practice: Identifying Barriers to Cardiovascular Health Management in Pediatric Type 1 Diabetes. The Journal of pediatrics Maahs, D. M. 2018; 197: 14?15

  View details for PubMedID 29551320

• Predictive hyperglycemia and hypoglycemia minimization: In-home double-blind randomized controlled evaluation in children and young adolescents PEDIATRIC DIABETES Forlenza, G. P., Raghinaru, D., Cameron, F., Bequette, B., Chase, H., Wadwa, R., Maahs, D. M., Jost, E., Ly, T. T., Wilson, D. M., Norlander, L., Ekhlaspour, L., Min, H., Clinton, P., Njeru, N., Lum, J. W., Kollman, C., Beck, R. W., Buckingham, B. A., In-Home Closed-Loop IHCL Study Grp 2018; 19 (3): 420?28

  Abstract

  The primary objective of this trial was to evaluate the feasibility, safety, and efficacy of a predictive hyperglycemia and hypoglycemia minimization (PHHM) system vs predictive low glucose suspension (PLGS) alone in optimizing overnight glucose control in children 6 to 14 years old.Twenty-eight participants 6 to 14 years old with T1D duration ?1?year with daily insulin therapy ?12 months and on insulin pump therapy for ?6?months were randomized per night into PHHM mode or PLGS-only mode for 42 nights. The primary outcome was percentage of time in sensor-measured range 70 to 180?mg/dL in the overnight period.The addition of automated insulin delivery with PHHM increased time in target range (70-180?mg/dL) from 66?±?11% during PLGS nights to 76?±?9% during PHHM nights (P<.001), without increasing hypoglycemia as measured by time below various thresholds. Average morning blood glucose improved from 176?±?28?mg/dL following PLGS nights to 154?±?19?mg/dL following PHHM nights (P<.001).The PHHM system was effective in optimizing overnight glycemic control, significantly increasing time in range, lowering mean glucose, and decreasing glycemic variability compared to PLGS alone in children 6 to 14 years old.

  View details for PubMedID 29159870

• Meta-genome-wide association studies identify a locus on chromosome 1 and multiple variants in the MHC region for serum C-peptide in type 1 diabetes DIABETOLOGIA Roshandel, D., Gubitosi-Klug, R., Bull, S. B., Canty, A. J., Pezzolesi, M. G., King, G. L., Keenan, H. A., Snell-Bergeon, J. K., Maahs, D. M., Klein, R., Klein, B. K., Orchard, T. J., Costacou, T., Weedon, M. N., Oram, R. A., Paterson, A. D., DCCT EDIC Res Grp 2018; 61 (5): 1098?1111

  Abstract

  The aim of this study was to identify genetic variants associated with beta cell function in type 1 diabetes, as measured by serum C-peptide levels, through meta-genome-wide association studies (meta-GWAS).We performed a meta-GWAS to combine the results from five studies in type 1 diabetes with cross-sectionally measured stimulated, fasting or random C-peptide levels, including 3479 European participants. The p values across studies were combined, taking into account sample size and direction of effect. We also performed separate meta-GWAS for stimulated (n?=?1303), fasting (n?=?2019) and random (n?=?1497) C-peptide levels.In the meta-GWAS for stimulated/fasting/random C-peptide levels, a SNP on chromosome 1, rs559047 (Chr1:238753916, T>A, minor allele frequency [MAF] 0.24-0.26), was associated with C-peptide (p?=?4.13?×?10-8), meeting the genome-wide significance threshold (p?T, MAF 0.07-0.10, p?=?8.43?×?10-8). In the stimulated C-peptide meta-GWAS, rs61211515 (Chr6:30100975, T/-, MAF 0.17-0.19) in the MHC region was associated with stimulated C-peptide (? [SE]?=?-?0.39 [0.07], p?=?9.72?×?10-8). rs61211515 was also associated with the rate of stimulated C-peptide decline over time in a subset of individuals (n?=?258) with annual repeated measures for up to 6 years (p?=?0.02). In the meta-GWAS of random C-peptide, another MHC region, SNP rs3135002 (Chr6:32668439, C>A, MAF 0.02-0.06), was associated with C-peptide (p?=?3.49?×?10-8). Conditional analyses suggested that the three identified variants in the MHC region were independent of each other. rs9260151 and rs3135002 have been associated with type 1 diabetes, whereas rs559047 and rs61211515 have not been associated with a risk of developing type 1 diabetes.We identified a locus on chromosome 1 and multiple variants in the MHC region, at least some of which were distinct from type 1 diabetes risk loci, that were associated with C-peptide, suggesting partly non-overlapping mechanisms for the development and progression of type 1 diabetes. These associations need to be validated in independent populations. Further investigations could provide insights into mechanisms of beta cell loss and opportunities to preserve beta cell function.

  View details for PubMedID 29404672

  View details for PubMedCentralID PMC5876265

• Fully Closed-Loop Multiple Model Probabilistic Predictive Controller Artificial Pancreas Performance in Adolescents and Adults in a Supervised Hotel Setting DIABETES TECHNOLOGY & THERAPEUTICS Forlenza, G. P., Cameron, F. M., Ly, T. T., Lam, D., Howsmon, D. P., Baysal, N., Kulina, G., Messer, L., Clinton, P., Levister, C., Patek, S. D., Levy, C. J., Wadwa, R., Maahs, D. M., Bequette, B., Buckingham, B. A. 2018; 20 (5): 335?43

  Abstract

  Initial Food and Drug Administration-approved artificial pancreas (AP) systems will be hybrid closed-loop systems that require prandial meal announcements and will not eliminate the burden of premeal insulin dosing. Multiple model probabilistic predictive control (MMPPC) is a fully closed-loop system that uses probabilistic estimation of meals to allow for automated meal detection. In this study, we describe the safety and performance of the MMPPC system with announced and unannounced meals in a supervised hotel setting.The Android phone-based AP system with remote monitoring was tested for 72?h in six adults and four adolescents across three clinical sites with daily exercise and meal challenges involving both three announced (manual bolus by patient) and six unannounced (no bolus by patient) meals. Safety criteria were predefined. Controller aggressiveness was adapted daily based on prior hypoglycemic events.Mean 24-h continuous glucose monitor (CGM) was 157.4?±?14.4?mg/dL, with 63.6?±?9.2% of readings between 70 and 180?mg/dL, 2.9?±?2.3% of readings <70?mg/dL, and 9.0?±?3.9% of readings >250?mg/dL. Moderate hyperglycemia was relatively common with 24.6?±?6.2% of readings between 180 and 250?mg/dL, primarily within 3?h after a meal. Overnight mean CGM was 139.6?±?27.6?mg/dL, with 77.9?±?16.4% between 70 and 180?mg/dL, 3.0?±?4.5% <70?mg/dL, 17.1?±?14.9% between 180 and 250?mg/dL, and 2.0?±?4.5%> 250?mg/dL. Postprandial hyperglycemia was more common for unannounced meals compared with announced meals (4-h postmeal CGM 197.8?±?44.1 vs. 140.6?±?35.0?mg/dL; P?

  View details for PubMedID 29658779

  View details for PubMedCentralID PMC5963546

• HUMAN FACTORS DURING TRIAL OF A HYBRID CLOSED LOOP SYSTEM FOR TYPE 1 DIABETES MANAGEMENT Adams, R. N., Tanenbaum, M. L., Hanes, S. J., Ambrosino, J. M., Ly, T. T., Maahs, D. M., Naranjo, D., Walders-Abramson, N., Weinzimer, S. A., Buckingham, B. A., Hood, K. K. OXFORD UNIV PRESS INC. 2018: S718

  View details for Web of Science ID 000431185202153

• Sex-specific differences in insulin resistance in type 1 diabetes: The CACTI cohort JOURNAL OF DIABETES AND ITS COMPLICATIONS Millstein, R. J., Pyle, L. L., Bergman, B. C., Eckel, R. H., Maahs, D. M., Rewers, M. J., Schauer, I. E., Snell-Bergeon, J. K. 2018; 32 (4): 418?23

  Abstract

  To test the hypothesis that multitissue deficits in insulin sensitivity are greater among women than men with type 1 diabetes compared to respective controls.Three-stage hyperinsulinemic-euglycemic clamps (4, 8, 40?mU/m2/min) were performed on 41 people with type 1 diabetes and 47 adults without diabetes (mean?±?SD age 46?±?8). Infusions of [1-13C]palmitate, [1,1,2,3,3-2H2]glycerol, and [6,6-2H2]glucose isotope tracers were used to determine free fatty acid (FFA), glycerol, and glucose kinetics in 52 of these participants (25?M and 27?W).There was no difference in age or BMI by type 1 diabetes status in either sex. Free fatty acid rate of appearance (FFA Ra) was higher in both sexes with type 1 diabetes compared to those without diabetes during stages 1 and 2. The same was seen with glycerol for stages 1 and 2. During stage 3 glucose rate of disappearance (Rd) was lower in those with type 1 diabetes among both sexes. All had sex by type 1 diabetes interactions with greater deficits in insulin sensitivity in women. While there was no sex by diabetes interaction in regards to glucose rate of appearance (Ra), those with type 1 diabetes had a higher glucose Ra than those without diabetes.We found that type 1 diabetes affected adipose and skeletal muscle insulin sensitivity to a greater extent in women than in men, perhaps contributing to the greater relative increase in cardiovascular risk in women with type 1 diabetes.

  View details for PubMedID 29449137

  View details for PubMedCentralID PMC5856232

• Role of bicarbonate supplementation on urine uric acid crystals and diabetic tubulopathy in adults with type 1 diabetes. Diabetes, obesity & metabolism Bjornstad, P., Maahs, D. M., Roncal, C. A., Snell-Bergeon, J. K., Shah, V. N., Milagres, T., Ellis, S. L., Hatch, M., Chung, L. T., Rewers, M. J., Garg, S., Cherney, D. Z., Pyle, L., Nadeau, K. J., Johnson, R. J. 2018

  Abstract

  Uricosuria and crystallization are increasingly recognized risk factors for diabetic tubulopathy. This pilot clinical trial aimed to determine the acute effect of urinary alkalinization using oral sodium bicarbonate (NaHCO3 ) on UA crystals in adults with type 1 diabetes (T1D). Adults with T1D, ages 18 to 65years (n=45, 60% female, HbA1c, 7.5±1.2%, 20.2±9.3 years duration) without chronic kidney disease (eGFR ?60mL/min/1.73m2 and albumin-to-creatinine ratio<30mg/g) received 2 doses of 1950mg oral NaHCO3 over 24hours. Fasting urine and serum were collected pre- and post-intervention. UA crystals were identified under polarized microscopy. Urine measurements included: osmolality, pH, UA, creatinine and kidney injury molecule-1 (KIM-1). NaHCO3 therapy increased mean±SD urine pH from 6.1±0.7 to 6.5±0.7 (P<.0001). Prior to therapy, 31.0% of participants had UA crystals vs 6.7% post therapy (P=.005). Change in urine pH inversely correlated with change in urine KIM-1 (r:-0.51, P=.0003). In addition, change in urine UA over 24hours correlated with change in urine KIM-1 (r:0.37, P=.01). In conclusion, oral NaHCO3 normalized urine pH and decreased UA crystals, and may hold promise as an inexpensive and safe tubulo-protective intervention in individuals with T1D.

  View details for PubMedID 29498467

• Quantifying genetic susceptibility in T1DM-implications for diagnosis after age 30 NATURE REVIEWS ENDOCRINOLOGY Meyer, E., Maahs, D. M. 2018; 14 (3): 134?35

  View details for PubMedID 29422635

• The Flexible Lifestyle Empowering Change (FLEX) intervention for self-management in adolescents with type 1 diabetes: Trial design and baseline characteristics CONTEMPORARY CLINICAL TRIALS Kichler, J. C., Seid, M., Crandell, J., Maahs, D. M., Bishop, F. K., Driscoll, K. A., Standiford, D., Hunter, C. M., Mayer-Davis, E. 2018; 66: 64?73

  Abstract

  The Flexible Lifestyle Empowering Change (FLEX) Intervention Study is a multi-site randomized controlled trial to test the efficacy of an adaptive behavioral intervention to promote self-management for youth with type 1 diabetes mellitus (T1D). This paper details FLEX design, demographic characteristics of the sample, and outcome variables at baseline. Participants were randomized to either an intervention or control arm after their baseline standardized measurement visit. Baseline data for the primary (glycemic levels) and secondary outcome variables (e.g., motivation and problem-solving, health-related quality of life, risk factors associated with T1D complications) as well as the potential mediator variables (e.g., self-management behavior, family conflict and responsibility) suggest that the study sample was representative of the general population of adolescents with T1D and their parents. The FLEX adaptive intervention is an innovative application of a tailored treatment intervention designed to be readily adopted in real-world practice to meet each adolescent's individualized T1D self-management goals.

  View details for PubMedID 29277316

  View details for PubMedCentralID PMC5828911

• Macrovascular disease and risk factors in youth with type 1 diabetes: time to be more attentive to treatment? The lancet. Diabetes & endocrinology Bjornstad, P., Donaghue, K. C., Maahs, D. M. 2018

  Abstract

  Cardiovascular disease remains the leading cause of mortality in patients with type 1 diabetes. Although cardiovascular disease complications are rare until adulthood, pathology and early markers can manifest in adolescence. Whereas advances have been made in the management of microvascular complications of type 1 diabetes, similar progress in reducing macrovascular complications has not been made. The reasons for the absence of progress remain incompletely understood, but most likely relate to the long time needed for cardiovascular disease to manifest clinically and hence for risk factor management to show a clinical benefit, thus allowing inertia to prevail for diagnosis and particularly for targeting risk factors. In this Review, we summarise paediatric data on traditional and novel risk factors of cardiovascular disease, provide an overview of data from previous and current clinical trials, discuss future directions in cardiovascular disease research for paediatric patients with type 1 diabetes, and advocate for the early identification and treatment of cardiovascular disease risk factors as recommended in multiple guidelines.

  View details for PubMedID 29475800

• Overnight Hypoglycemia and Hyperglycemia Mitigation for Individuals with Type 1 Diabetes HOW RISKS CAN BE REDUCED IEEE CONTROL SYSTEMS MAGAZINE Bequette, B., Cameron, F., Buckingham, B. A., Maahs, D. M., Lum, J. 2018; 38 (1): 125?34

  View details for DOI 10.1109/MCS.2017.2767119

  View details for Web of Science ID 000423203300013

• The dawn of automated insulin delivery: A new clinical framework to conceptualize insulin administration PEDIATRIC DIABETES Messer, L. H., Forlenza, G. P., Wadwa, R., Weinzimer, S. A., Sherr, J. L., Hood, K. K., Buckingham, B. A., Slover, R. H., Maahs, D. M. 2018; 19 (1): 14?17

  View details for PubMedID 28656656

• Diabetes technology: improving care, improving patient-reported outcomes and preventing complications in young people with Type 1 diabetes. Diabetic medicine : a journal of the British Diabetic Association Prahalad, P., Tanenbaum, M., Hood, K., Maahs, D. M. 2018

  Abstract

  With the evolution of diabetes technology, those living with Type 1 diabetes are given a wider arsenal of tools with which to achieve glycaemic control and improve patient-reported outcomes. Furthermore, the use of these technologies may help reduce the risk of acute complications, such as severe hypoglycaemia and diabetic ketoacidosis, as well as long-term macro- and microvascular complications. In addition, diabetes technology can have a beneficial impact on psychosocial health by reducing the burden of diabetes. Unfortunately, diabetes goals are often unmet and people with Type 1 diabetes too frequently experience acute and long-term complications of this condition, in addition to often having less than ideal psychosocial outcomes. Increasing realization of the importance of patient-reported outcomes is leading to diabetes care delivery becoming more patient-centred. Diabetes technology in the form of medical devices, digital health and big data analytics have the potential to improve clinical care and psychosocial support, resulting in lower rates of acute and chronic complications, decreased burden of diabetes care, and improved quality of life. This article is protected by copyright. All rights reserved.

  View details for PubMedID 29356074

• Real-Time Detection of Infusion Site Failures in a Closed-Loop Artificial Pancreas. Journal of diabetes science and technology Howsmon, D. P., Baysal, N., Buckingham, B. A., Forlenza, G. P., Ly, T. T., Maahs, D. M., Marcal, T., Towers, L., Mauritzen, E., Deshpande, S., Huyett, L. M., Pinsker, J. E., Gondhalekar, R., Doyle, F. J., Dassau, E., Hahn, J., Bequette, B. W. 2018; 12 (3): 599?607

  Abstract

  BACKGROUND: As evidence emerges that artificial pancreas systems improve clinical outcomes for patients with type 1 diabetes, the burden of this disease will hopefully begin to be alleviated for many patients and caregivers. However, reliance on automated insulin delivery potentially means patients will be slower to act when devices stop functioning appropriately. One such scenario involves an insulin infusion site failure, where the insulin that is recorded as delivered fails to affect the patient's glucose as expected. Alerting patients to these events in real time would potentially reduce hyperglycemia and ketosis associated with infusion site failures.METHODS: An infusion site failure detection algorithm was deployed in a randomized crossover study with artificial pancreas and sensor-augmented pump arms in an outpatient setting. Each arm lasted two weeks. Nineteen participants wore infusion sets for up to 7 days. Clinicians contacted patients to confirm infusion site failures detected by the algorithm and instructed on set replacement if failure was confirmed.RESULTS: In real time and under zone model predictive control, the infusion site failure detection algorithm achieved a sensitivity of 88.0% (n = 25) while issuing only 0.22 false positives per day, compared with a sensitivity of 73.3% (n = 15) and 0.27 false positives per day in the SAP arm (as indicated by retrospective analysis). No association between intervention strategy and duration of infusion sets was observed ( P = .58).CONCLUSIONS: As patient burden is reduced by each generation of advanced diabetes technology, fault detection algorithms will help ensure that patients are alerted when they need to manually intervene. Clinical Trial Identifier: www.clinicaltrials.gov,NCT02773875.

  View details for PubMedID 29390915

• Increasing Use of Continuous Glucose Monitoring (CGM) Among Youth with Type 1 Diabetes (T1D): Icomparison of Youth from the T1D Exchange (T1DX) and the DPV Initiative Miller, K., Hermann, J., Maahs, D., Hofer, S., Foster, N., Holl, R. KARGER. 2018: 219?20

  View details for Web of Science ID 000445204101204

• Age at type 1 diabetes onset: a new risk factor and call for focused treatment. Lancet (London, England) Basina, M., Maahs, D. M. 2018; 392 (10146): 453?54

  View details for PubMedID 30129445

• 50 Years Ago in The Journal of Pediatrics: Familial Holoprosencephaly with Endocrine Dysgenesis. The Journal of pediatrics Chang, M., Wilson, D. M., Maahs, D. M. 2018; 192: 98

  View details for PubMedID 29246365

• ISPAD Annual Conference 2017 Highlights. Pediatric diabetes Agwu, J. C., Idkowiak, J., Bull, L., Ng, S. M., Dov?, K., Ngwu, U., Calliari, L. E., Maahs, D. M. 2018; 19 (5): 855?58

  View details for PubMedID 29968361

• Measured GFR in Routine Clinical Practice-The Promise of Dried Blood Spots ADVANCES IN CHRONIC KIDNEY DISEASE Bjornstad, P., Karger, A. B., Maahs, D. M. 2018; 25 (1): 76?83

  Abstract

  Accurate determination of glomerular filtration rate (GFR) is crucial for the diagnosis of kidney disease. Estimated GFR (eGFR) calculated by serum creatinine and/or cystatin C is a mainstay in clinical practice and epidemiologic research but lacks precision and accuracy until GFR <60 mL/min/1.73 m2. Furthermore, eGFR may not precisely and accurately represent changes in GFR longitudinally. The lack of precision and accuracy is of concern in populations at high risk for kidney disease, as the dissociation between changes in eGFR and GFR may lead to missed diagnoses of early kidney disease. Therefore, improved methods to quantify GFR are needed. Whereas direct measures of GFR have been too cumbersome for screening and ambulatory care, a practical method of measuring GFR by iohexol clearance using dried capillary blood spots exists. In this review, we examine the current literature and data addressing GFR measurements by dried capillary blood spots and its potential application in high-risk groups.

  View details for PubMedID 29499891

  View details for PubMedCentralID PMC5836491

• Familial Holoprosencephaly with Endocrine Dysgenesis JOURNAL OF PEDIATRICS Chang, M., Wilson, D. M., Maahs, D. M. 2018; 192: 98

  View details for Web of Science ID 000423353900019

• Dynamic changes in retinal vessel diameter during acute hyperglycemia in type 1 diabetes. Journal of diabetes and its complications Bucca, B. C., Maahs, D. M., Snell-Bergeon, J. K., Hokanson, J., Rinella, S., Bishop, F., Boufard, A., Homann, J., Cheung, C. Y., Wong, T. Y. 2018; 32 (2): 234?39

  Abstract

  To investigate changes in retinal vessel diameter during acute hyperglycemia in patients with type 1 diabetes.We conducted a study on 11 subjects with type 1 diabetes. Euglycemia was maintained for 3h followed by induction of hyperglycemia and simultaneous bolus of rapid acting insulin. Two fundus photos were captured during euglycemia and five fundus photos, blood glucose and blood pressure were taken every 30min for 2.5h post-prandial. Central retinal artery equivalent (CRAE) and central retinal vein equivalent (CRVE) were measured over the study visit and examined using generalized linear mixed models.In a multivariate mixed model, mean CRAE and CRVE were reduced at 90min post-prandial in both zones B and C. In repeated measures analysis, arterioles exhibited a significant association with change in vessel caliber per change in blood glucose. Inconsistent effects of blood pressure on vessel diameter were also measured.We document a change in retinal vessel diameter during acute hyperglycemia in persons with type 1 diabetes. Larger controlled studies are required to further investigate this phenomenon and to more accurately assess if hyperglycemia has direct effects on retinal vessel diameter.

  View details for PubMedID 29174301

• Diabetes Technology and Therapy in the Pediatric Age Group. Diabetes technology & therapeutics Maahs, D. M., Shalitin, S. 2018; 20 (S1): S114?S127

  View details for DOI 10.1089/dia.2018.2510

  View details for PubMedID 29437470

• Optimizing Hybrid Closed-Loop Therapy in Adolescents and Emerging Adults Using the MiniMed 670G System. Diabetes care Messer, L. H., Forlenza, G. P., Sherr, J. L., Wadwa, R. P., Buckingham, B. A., Weinzimer, S. A., Maahs, D. M., Slover, R. H. 2018; 41 (4): 789?96

  Abstract

  The MiniMed 670G System is the first commercial hybrid closed-loop (HCL) system for management of type 1 diabetes. Using data from adolescent and young adult participants, we compared insulin delivery patterns and time-in-range metrics in HCL (Auto Mode) and open loop (OL). System alerts, usage profiles, and operational parameters were examined to provide suggestions for optimal clinical use of the system.Data from 31 adolescent and young adult participants (14-26 years old) at three clinical sites in the 670G pivotal trial were analyzed. Participants had a 2-week run-in period in OL, followed by a 3-month in-home study phase with HCL functionality enabled. Data were compared between baseline OL and HCL use after 1 week, 1 month, 2 months, and 3 months.Carbohydrate-to-insulin (C-to-I) ratios were more aggressive for all meals with HCL compared with baseline OL. Total daily insulin dose and basal-to-bolus ratio did not change during the trial. Time in range increased 14% with use of Auto Mode after 3 months (P< 0.001), and HbA1cdecreased 0.75%. Auto Mode exits were primarily due to sensor/insulin delivery alerts and hyperglycemia. The percentage of time in Auto Mode gradually declined from 87%, with a final use rate of 72% (-15%).In transitioning young patients to the 670G system, providers should anticipate immediate C-to-I ratio adjustments while also assessing active insulin time. Users should anticipate occasional Auto Mode exits, which can be reduced by following system instructions and reliably bolusing for meals. Unique 670G system functionality requires ongoing clinical guidance and education from providers.

  View details for PubMedID 29444895

• Effect of Oral Insulin on Prevention of Diabetes in Relatives of Patients With Type 1 Diabetes A Randomized Clinical Trial JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION Greenbaum, C., Atkinson, M., Baidal, D., Battaglia, M., Bingley, P., Bosi, E., Buckner, J., Clements, M., Colman, P., DiMeglio, L., Evans-Molina, C., Gitelman, S., Goland, R., Gottlieb, P., Herold, K., Knip, M., Krischer, J., Lernmark, A., Moore, W., Moran, A., Muir, A., Palmer, J., Peakman, M., Philipson, L., Raskin, P., Redondo, M., Rodriguez, H., Russell, W., Spain, L., Schatz, D. A., Sosenko, J., Wherrett, D., Wilson, D., Winter, W., Ziegler, A., Anderson, M., Antinozzi, P., Benoist, C., Blum, J., Bourcier, K., Chase, P., Clare-Salzler, M., Clynes, R., Cowie, C., Eisenbarth, G., Fathman, C. G., Grave, G., Harrison, L., Hering, B., Insel, R., Jordan, S., Kaufman, F., Kay, T., Kenyon, N., Klines, R., Lachin, J., Leschek, E., Mahon, J., Marks, J. B., Monzavi, R., Nanto-Salonen, K., Nepom, G., Orban, T., Parkman, R., Pescovitz, M., Peyman, J., Pugliese, A., Ridge, J., Roep, B., Roncarolo, M., Savage, P., Simell, O., Sherwin, R., Siegelman, M., Skyler, J. S., Thomas, J., Trucco, M., Wagner, J., Bourcier, K., Greenbaum, C. J., Krischer, J. P., Leschek, E., Rafkin, L., Spain, L., Cowie, C., Foulkes, M., Insel, R., Krause-Steinrauf, H., Lachin, J. M., Malozowski, S., Peyman, J., Ridge, J., Savage, P., Skyler, J. S., Zafonte, S. J., Greenbaum, C. J., Rafkin, L., Sosenko, J., Skyler, J. S., Kenyon, N. S., Santiago, I., Krischer, J. P., Bundy, B., Abbondondolo, M., Adams, T., Asif, D., Boonstra, M., Boulware, D., Bundy, B., Burroughs, C., Cuthbertson, D., Eberhard, C., Fiske, S., Ford, J., Garmeson, J., Guillette, H., Geyer, S., Hays, B., Henderson, C., Henry, M., Heyman, K., Hsiao, B., Karges, C., Kinderman, A., Lane, L., Leinbach, A., Liu, S., Lloyd, J., Malloy, J., Maddox, K., Martin, J., Miller, J., Moore, M., Muller, S., Nguyen, T., O'Donnell, R., Parker, M., Pereyra, M. J., Reed, N., Roberts, A., Sadler, K., Stavros, T., Tamura, R., Wood, K., Xu, P., Young, K., Alies, P., Badias, F., Baker, A., Bassi, M., Beam, C., Boulware, D., Bounmananh, L., Bream, S., Deemer, M., Freeman, D., Gough, J., Ginem, J., Granger, M., Holloway, M., Kieffer, M., Lane, P., Law, P., Linton, C., Nallamshetty, L., Oduah, V., Parrimon, Y., Paulus, K., Pilger, J., Ramiro, J., Ritzie, A., Sharma, A., Shor, A., Song, X., Terry, A., Weinberger, J., Wootten, M., Lachin, J. M., Harding, M., Krause-Steinrauf, H., McDonough, S., Mcgee, P. F., Hess, K., Phoebus, D., Quinlan, S., Raiden, E., Fradkin, J., Leschek, E., Spain, L., Cowie, C., Malozowski, S., Savage, P., Beck, G., Blumberg, E., Gubitosi-Klug, R., Laffel, L., Veatch, R., Wallace, D., Braun, J., Brillon, D., Lernmark, A., Lo, B., Mitchell, H., Naji, A., Nerup, J., Orchard, T., Steffes, M., Tsiatis, A., Zinman, B., Loechelt, B., Baden, L., Green, M., Weinberg, A., Marcovina, S., Palmer, J. P., Weinberg, A., Yu, L., Winter, W., Shultz, A., Batts, E., Fitzpatrick, K., Ramey, M., Guerra, R., Webb, C., Caffey, F., Carr, L., Ergun-Longmire, B., Fenton, C., Giebner, D., Johnson, J., Maglionico, D., Marinelli, M., Martin, K., Minnozzi, E., Riley, W., Wilson, M., Gougeon, C., Ho, J., Huang, C., Pacaud, D., Virtanen, H., Craig, C., Ghatak, A., Henderson, T., Leyland, H., Padmore, K., Paul, P., Brickman, W., Halsey-Lyda, M., Petrie, P., Rizzo, D., Steuer, R., Suchyta, K., Torchen, L., Zimmerman, D., Bode, B., Dial, M., Gazaway, K., Hosey, R., Alkanani, A., Barker, J., Barr, M., Blau, A., Burdick, P., Burke, B., Chase, H., Drye, M., Eisenbarth, G., Escobar, E., Fitzgerald-Miller, L., Fouts, A., Gage, V., Gall, E., Goettle, H., Gottlieb, P., Harris, S., Ketchum, K., King, M., Klingensmith, G., Lehr, D., Lehr, J., Lewis, L., Logsden-Sackett, N., Lykens, J., Maahs, D., Michels, A., Pelletier, S., Rihanek, M., Rodriguez, P., Schauwecker, A., Simmons, K., Smith, J., Steck, A., Tran, B., 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M., Auerback, G., Berhel, A., Bomberg, E., Breen, K., Buchanan, J., Cook, A., Cakmak, A., Ferrara, C., Fields, S., Finney, Z., Fraser, K., Gonzalez, A., Ghods, S., Gitelman, S., Hamid, L., Hamilton, C., Hawkins, L., Honrada, R., Huang, A., Jain, A., Jossan, P., Ko, K., Larocque, N., Lilley, B., Long, R., Lustig, D. R., Ly, E., Malik, A., Melaku, A., Moassesfar, S., Mugg, A., Ng, D., Ng, D., O'Brien, C., Perez, E., Phelps, S., Prahalod, P., Ramos, E., Lugo, M., Rodriguez, T., Arao, A., Demeterco-Berggren, C., Duong, J., Gottschalk, M., Hashiguchi, M., Kelly, T., Marinkovic, M., Marois, N., Newfield, R., Phillips, S., Rosenblum, D., Abdullah, N., Dunger, D., Gilbert, A., Guy, C., Hendricks, E., May, J., O'Brien, C., Salgin, B., Thankamony, A., Vyse, N., Watts, A., Whitehead, K., Whitehead, L., Willemsen, R., Williams, R., Wingate, D., Devine, N., Gannon, G., Grant, T., Letourneau, L., Littlejohn, E., Norstrom, M., O'Malley, T., Philipson, L., Abraham, A., Agustin, E., Albanese-O'Neill, A., Beltz, S., Clare-Salzler, M., Cole, G., Cook, R., Coy, R., Ferguson, J., Ferguson, R., Haller, M., Hicks, E., Hosford, J., Jacobsen, L., Johnson, M., Kahler, D., Kerr, N., Kimsey, R., Lucas, A., Meehan, C., Paguio, G., Rohrs, H., Schatz, D., Smith, M., Thomas, J., Towe, P., White, D., Winter, W., Zimmerman, C., Hamalainen, J., Harkonen, T., Helander, S., Hero, M., Hirvasniemi, M., Isoaho, K., Jaminki, S., Joutsjoki, L., Kalliola, P., Kararic, M., Knip, M., Koski, K., Koski, M., Koski, M. L., Koskinen, M., Kytola, J., Laamanen, T., Latva-Koivisto, M., Laurinen, S., Mustila, T., Nyblom, M., Ollila, I., Pekkola, M., Salonen, K., Selvenius, J., Siljamaki, S., Siljander, H., Snygg, S., Suomalainen, H., Suomi, A., Tuomaala, A., Cabbage, J., Coffey, J., Hobbs, T., Johnson, K., Martin, M., Rosazza, S., Tansey, M., Tsalikian, E., Deuser, A., Foster, M., Pierce, G., Rayborn, L., Rodriguez-Luna, M., Rush, H., Wintergerst, K., Bloomfield, E., Catte, D., Dean, H., Ferens, H., Kerr, L., Kozak, B., Maharaj, R., Marks, S., Minuk, L., Rossum, K., Sneesby, K., Stierman, T., Sucharov-Benarroch, A., Taback, S., Woo, V., Yakimoski, A., Allende, G., Arazo, L., Arce, R., Baidal, D., Blaschke, C., Marks, J., Matheson, D., Pugliese, A., Sanders-Branca, N., Snowhite, I., Burant, C., Chen, M., Haddad, A., Herman, W., Hooks, H., Martin, C., Menon, R., Pietropaolo, M., Pietropaolo, S., Plunkett, C., Pop-Busui, R., Soleimanpour, A., Surhigh, J., Thomas, I., Wood, M., Bartyzal, A., Christianson, T., Flaherty, N., Forlenza, G., Gibson, C., Halper, A., Halvorsen, T., Hamdoun, E., Helms, H., Kwong, C., Lee, C., Leschyshyn, J., Luke, D., McVean, J., Moran, T., Nathan, B., Nelson, B., Omann, T., Pappenfus, B., Parchem, B., Storo, K., Street, A., Sunni, M., Tafuri, M., Vang, N., Weingartner, D., Becker, D., DeLallo, K., Diaz, A., Elnyczky, B., Groscost, D., Baldauff, N., Hoffmann, P., Ismail, H., Klein, M., Lamm, V., Libman, I., McDowell, K., Minshall, V., Pasek, B., Riley, K., Shelleby, C., Sigmund, L., Smith, M., Tas, E., Trucco, M., Yates, C., Artman, H., Johnson, B., Jospe, N., Miller, A., Orlowski, C., Jackson, M., Johnson, B., Knight, L., Szadek, L., Thompson, B., Welnick, G., Al-Zubeidi, H., Bansal, S., Bissler, M., Carroll, L., Cockroft, J., Dourisseau, D., Ferry, R., Foster, C., Johnson, T., Kassim, N., Lee, K., Logan, B., Mazhar, G., McCommon, D., Moisan, A., Parish, M., Sands, C., Sinha, S., Smith, L., Thomas, A., Thompson, L., Trzil, J., Wilson, N., Green, L., Harden, T., Kreymer, R., Mohan, A., Pruneda, M., Raskin, P., Richard, J., Schnurr-Breen, L., Smith, O., Sturges, D., Torres, N., Ziemian, L., Allred, M., Baker, S., Calder, T., Dansie, P., Donaldson, D., Foster, C., Garcia, E., Jarrett, K., Langvardt, J., Lener, M., Lusted, K., Murray, M., Reynolds, L., Slater, H., Thompson, D., Underlin, K., Vickers, L., Wheeler, K., Bere, L., Clarson, C., Gallego, P., Lovell, M., Mahon, J., McCallum, J., Stein, R., Babington, B., Barnes, K., Black, M., Bremer, A., Brendle, F., Brown, A., Dixon, B., Frazier, E., Gregg, A., Moore, D., Mountz, G., Olayinka, K., Pittel, E., Robertson, A., Russell, W., Shah, K., Shannon, A., Thomas, J., Yoder, S., Anderson, T., Bailey, D., Basnet, D., Branch, M., Bruce, G., Francis, G., Hagan, S., Henderson, G., Khandan-Barani, M., King, T., Le, T., Lemmons, J., Miller, M., Nesgoda, L., Penn, M., Schmid, J., Shankar, R., Usry, M., Wickham, E., Banks, W., Brown, H., Constantino, M., Hutson, J., Kellum, G., Lagarde, W., Lewis, M., Lockemer, H., McLaughlin, T., Piszczak, M., Reif, S., Vanderploeg, T., Andaloro, E., Breen, C., Colman, P., Dalgleish, N., Fourlanos, S., Gellert, S., Harrison, L., Healy, F., Hong, E., Hsieh, C., Mesfin, S., Mohammed, E., Redl, L., Watson, K., Wentworth, J., Cresswell, P., Faherty, H., Gould, A., Healy, F., Krebs, J., Maister, C., Ross, C., Wiltshire, E., Beresford, S., Campbell, S., Cortis, L., Couper, J., Cranwell, A., Fairchild, J., Healy, F., Richichi, K., Abdelghany, O., Feldman, L., Forbes, N., Herold, K., Huang, Y., Kunze, K., Rink, L., Sherr, J., Sherwin, R., Tamborlane, W., Weinzimer, S., Wurtz, A., Yama, N., Young, L., Writing Comm Type Diabet 2017; 318 (19): 1891?1902

  Abstract

  Type 1 diabetes requires major lifestyle changes and carries increased morbidity and mortality. Prevention or delay of diabetes would have major clinical effect.To determine whether oral insulin delays onset of type 1 diabetes in autoantibody-positive relatives of patients with type 1 diabetes.Between March 2, 2007, and December 21, 2015, relatives with at least 2 autoantibodies, including insulin autoantibodies and normal glucose tolerance, were enrolled in Canada, the United States, Australia, New Zealand, the United Kingdom, Italy, Sweden, Finland, and Germany. The main study group (n?=?389) had first-phase insulin release on an intravenous glucose tolerance test that was higher than the threshold. The 55 patients in the secondary stratum 1 had an identical antibody profile as the main study group except they had first-phase insulin release that was lower than the threshold. Secondary strata 2 (n?=?114) and strata 3 (n?=?3) had different autoantibody profiles and first-phase insulin release threshold combinations. Follow-up continued through December 31, 2016.Randomization to receive 7.5 mg/d of oral insulin (n?=?283) or placebo (n?=?277), including participants in the main study group who received oral insulin (n?=?203) or placebo (n?=?186).The primary outcome was time to diabetes in the main study group. Significance was based on a 1-sided threshold of .05, and 1-sided 95% CIs are reported.Of a total of 560 randomized participants (median enrollment age, 8.2 years; interquartile range [IQR], 5.7-12.1 years; 170 boys [60%]; 90.7% white non-Hispanic; 57.6% with a sibling with type 1 diabetes), 550 completed the trial including 389 participants (median age, 8.4 years; 245 boys [63%]), 382 (96%) in the main study group. During a median follow-up of 2.7 years (IQR, 1.5-4.6 years) in the main study group, diabetes was diagnosed in 58 participants (28.5%) in the oral insulin group and 62 (33%) in the placebo group. Time to diabetes was not significantly different between the 2 groups (hazard ratio [HR], 0.87; 95% CI, 0-1.2; P?=?.21). In secondary stratum 1 (n?=?55), diabetes was diagnosed in 13 participants (48.1%) in the oral insulin group and in 19 participants (70.3%) in the placebo group. The time to diabetes was significantly longer with oral insulin (HR, 0.45; 95% CI, 0-0.82; P?=?.006). The HR for time to diabetes for the between-group comparisons for the 116 participants in the other secondary stratum was 1.03 (95% CI, 0-2.11; P?=?.53) and for the entire cohort of 560 participants was 0.83 (95% CI, 0-1.07; P?=?.11), which were not significantly different. The most common adverse event was infection (n?=?254), with 134 events in the oral insulin group and 120 events in the placebo group, but no significant study-related adverse events occurred.Among autoantibody-positive relatives of patients with type 1 diabetes, oral insulin at a dose of 7.5 mg/d, compared with placebo, did not delay or prevent the development of type 1 diabetes over 2.7 years. These findings do not support oral insulin as used in this study for diabetes prevention.clinicaltrials.gov Identifier: NCT00419562.

  View details for DOI 10.1001/jama.2017.17070

  View details for Web of Science ID 000415870300019

  View details for PubMedID 29164254

  View details for PubMedCentralID PMC5798455

• A Meta Genome-Wide Association Study Identifies a Novel Locus for Cardiovascular Disease in Type 1 Diabetes Keshavarzi, S., Canty, A., Klein, B. K., Trevor, O. J., Costacou, T., Klein, R., Snell-Bergeon, J., Maahs, D., Miller, R., Lee, K. E., Paterson, A. D. WILEY. 2017: 657?58

  View details for Web of Science ID 000413035000044

• Trust in hybrid closed loop among people with diabetes: Perspectives of experienced system users. Journal of health psychology Tanenbaum, M. L., Iturralde, E., Hanes, S. J., Suttiratana, S. C., Ambrosino, J. M., Ly, T. T., Maahs, D. M., Naranjo, D., Walders-Abramson, N., Weinzimer, S. A., Buckingham, B. A., Hood, K. K. 2017: 1359105317718615

  Abstract

  Automated closed loop systems will greatly change type 1 diabetes management; user trust will be essential for acceptance of this new technology. This qualitative study explored trust in 32 individuals following a hybrid closed loop trial. Participants described how context-, system-, and person-level factors influenced their trust in the system. Participants attempted to override the system when they lacked trust, while trusting the system decreased self-management burdens and decreased stress. Findings highlight considerations for fostering trust in closed loop systems. Systems may be able to engage users by offering varying levels of controls to match trust preferences.

  View details for PubMedID 28810490

• Application of Zone Model Predictive Control Artificial Pancreas During Extended Use of Infusion Set and Sensor: A Randomized Crossover-Controlled Home-Use Trial. Diabetes care Forlenza, G. P., Deshpande, S., Ly, T. T., Howsmon, D. P., Cameron, F., Baysal, N., Mauritzen, E., Marcal, T., Towers, L., Bequette, B. W., Huyett, L. M., Pinsker, J. E., Gondhalekar, R., Doyle, F. J., Maahs, D. M., Buckingham, B. A., Dassau, E. 2017

  Abstract

  As artificial pancreas (AP) becomes standard of care, consideration of extended use of insulin infusion sets (IIS) and continuous glucose monitors (CGMs) becomes vital. We conducted an outpatient randomized crossover study to test the safety and efficacy of a zone model predictive control (zone-MPC)-based AP system versus sensor augmented pump (SAP) therapy in which IIS and CGM failures were provoked via extended wear to 7 and 21 days, respectively.A smartphone-based AP system was used by 19 adults (median age 23 years [IQR 10], mean 8.0 ± 1.7% HbA1c) over 2 weeks and compared with SAP therapy for 2 weeks in a crossover, unblinded outpatient study with remote monitoring in both study arms.AP improved percent time 70-140 mg/dL (48.1 vs. 39.2%; P = 0.016) and time 70-180 mg/dL (71.6 vs. 65.2%; P = 0.008) and decreased median glucose (141 vs. 153 mg/dL; P = 0.036) and glycemic variability (SD 52 vs. 55 mg/dL; P = 0.044) while decreasing percent time <70 mg/dL (1.3 vs. 2.7%; P = 0.001). AP also improved overnight control, as measured by mean glucose at 0600 h (140 vs. 158 mg/dL; P = 0.02). IIS failures (1.26 ± 1.44 vs. 0.78 ± 0.78 events; P = 0.13) and sensor failures (0.84 ± 0.6 vs. 1.1 ± 0.73 events; P = 0.25) were similar between AP and SAP arms. Higher percent time in closed loop was associated with better glycemic outcomes.Zone-MPC significantly and safely improved glycemic control in a home-use environment despite prolonged CGM and IIS wear. This project represents the first home-use AP study attempting to provoke and detect component failure while successfully maintaining safety and effective glucose control.

  View details for DOI 10.2337/dc17-0500

  View details for PubMedID 28584075

• Prevalence of Celiac Disease in 52,721 Youth With Type 1 Diabetes: International Comparison Across Three Continents. Diabetes care Craig, M. E., Prinz, N., Boyle, C. T., Campbell, F. M., Jones, T. W., Hofer, S. E., Simmons, J. H., Holman, N., Tham, E., Fröhlich-Reiterer, E., Dubose, S., Thornton, H., King, B., Maahs, D. M., Holl, R. W., Warner, J. T. 2017

  Abstract

  Celiac disease (CD) has a recognized association with type 1 diabetes. We examined international differences in CD prevalence and clinical characteristics of youth with coexisting type 1 diabetes and CD versus type 1 diabetes only.Data sources were as follows: the Prospective Diabetes Follow-up registry (Germany/Austria); the T1D Exchange Clinic Network (T1DX) (U.S.); the National Paediatric Diabetes Audit (U.K. [England/Wales]); and the Australasian Diabetes Data Network (ADDN) (Australia). The analysis included 52,721 youths <18 years of age with a clinic visit between April 2013 and March 2014. Multivariable linear and logistic regression models were constructed to analyze the relationship between outcomes (HbA1c, height-standard deviation score [SDS], overweight/obesity) and type 1 diabetes/CD versus type 1 diabetes, adjusting for sex, age, and diabetes duration.Biopsy-confirmed CD was present in 1,835 youths (3.5%) and was diagnosed at a median age of 8.1 years (interquartile range 5.3-11.2 years). Diabetes duration at CD diagnosis was <1 year in 37% of youths, >1-2 years in 18% of youths, >3-5 years in 23% of youths, and >5 years in 17% of youths. CD prevalence ranged from 1.9% in the T1DX to 7.7% in the ADDN and was higher in girls than boys (4.3% vs. 2.7%, P < 0.001). Children with coexisting CD were younger at diabetes diagnosis compared with those with type 1 diabetes only (5.4 vs. 7.0 years of age, P < 0.001) and fewer were nonwhite (15 vs. 18%, P < 0.001). Height-SDS was lower in those with CD (0.36 vs. 0.48, adjusted P < 0.001) and fewer were overweight/obese (34 vs. 37%, adjusted P < 0.001), whereas mean HbA1c values were comparable: 8.3 ± 1.5% (67 ± 17 mmol/mol) versus 8.4 ± 1.6% (68 ± 17 mmol/mol).CD is a common comorbidity in youth with type 1 diabetes. Differences in CD prevalence may reflect international variation in screening and diagnostic practices, and/or CD risk. Although glycemic control was not different, the lower height-SDS supports close monitoring of growth and nutrition in this population.

  View details for DOI 10.2337/dc16-2508

  View details for PubMedID 28546222

• Clinical Use of Continuous Glucose Monitoring in Pediatrics. Diabetes technology & therapeutics Lal, R. A., Maahs, D. M. 2017; 19 (S2): S37-S43

  View details for DOI 10.1089/dia.2017.0013

  View details for PubMedID 28541138

• Outpatient Closed-Loop Control with Unannounced Moderate Exercise in Adolescents Using Zone Model Predictive Control. Diabetes technology & therapeutics Huyett, L. M., Ly, T. T., Forlenza, G. P., Reuschel-DiVirgilio, S., Messer, L. H., Wadwa, R. P., Gondhalekar, R., Doyle, F. J., Pinsker, J. E., Maahs, D. M., Buckingham, B. A., Dassau, E. 2017

  Abstract

  The artificial pancreas (AP) has the potential to improve glycemic control in adolescents. This article presents the first evaluation in adolescents of the Zone Model Predictive Control and Health Monitoring System (ZMPC+HMS) AP algorithms, and their first evaluation in a supervised outpatient setting with frequent exercise.Adolescents with type 1 diabetes underwent 3 days of closed-loop control (CLC) in a hotel setting with the ZMPC+HMS algorithms on the Diabetes Assistant platform. Subjects engaged in twice-daily exercise, including soccer, tennis, and bicycling. Meal size (unrestricted) was estimated and entered into the system by subjects to trigger a bolus, but exercise was not announced.Ten adolescents (11.9-17.7 years) completed 72?h of CLC, with data on 95?±?14?h of sensor-augmented pump (SAP) therapy before CLC as a comparison to usual therapy. The percentage of time with continuous glucose monitor (CGM) 70-180?mg/dL was 71%?±?10% during CLC, compared to 57%?±?16% during SAP (P?=?0.012). Nocturnal control during CLC was safe, with 0% (0%, 0.6%) of time with CGM <70?mg/dL compared to 1.1% (0.0%, 14%) during SAP. Despite large meals (estimated up to 120?g carbohydrate), only 8.0%?±?6.9% of time during CLC was spent with CGM >250?mg/dL (16%?±?14% during SAP). The system remained connected in CLC for 97%?±?2% of the total study time. No adverse events or severe hypoglycemia occurred.The use of the ZMPC+HMS algorithms is feasible in the adolescent outpatient environment and achieved significantly more time in the desired glycemic range than SAP in the face of unannounced exercise and large announced meal challenges.

  View details for DOI 10.1089/dia.2016.0399

  View details for PubMedID 28459617

• Dietary intake and risk of non-severe hypoglycemia in adolescents with type 1 diabetes. Journal of diabetes and its complications Zhong, V. W., Crandell, J. L., Shay, C. M., Gordon-Larsen, P., Cole, S. R., Juhaeri, J., Kahkoska, A. R., Maahs, D. M., Seid, M., Forlenza, G. P., Mayer-Davis, E. J. 2017

  Abstract

  To determine the association between dietary intake and risk of non-severe hypoglycemia in adolescents with type 1 diabetes.Type 1 adolescents from a randomized trial wore a blinded continuous glucose monitoring (CGM) system at baseline for one week in free-living conditions. Dietary intake was calculated as the average from two 24-h dietary recalls. Non-severe hypoglycemia was defined as having blood glucose <70mg/dL for ?10min but not requiring external assistance, categorized as daytime and nocturnal (11PM-7AM). Data were analyzed using logistic regression models.Among 98 participants with 14,277h of CGM data, 70 had daytime hypoglycemia, 66 had nocturnal hypoglycemia, 55 had both, and 17 had neither. Soluble fiber and protein intake were positively associated with both daytime and nocturnal hypoglycemia. Glycemic index, monounsaturated fat, and polyunsaturated fat were negatively associated with daytime hypoglycemia only. Adjusting for total daily insulin dose per kilogram eliminated all associations.Dietary intake was differentially associated with daytime and nocturnal hypoglycemia. Over 80% of type 1 adolescents had hypoglycemia in a week, which may be attributed to the mismatch between optimal insulin dose needed for each meal and actually delivered insulin dose without considering quality of carbohydrate and nutrients beyond carbohydrate.ClinicalTrials.gov identifier: NCT01286350.

  View details for DOI 10.1016/j.jdiacomp.2017.04.017

  View details for PubMedID 28476567

• Expectations and Attitudes of Individuals With Type 1 Diabetes After Using a Hybrid Closed Loop System DIABETES EDUCATOR Iturralde, E., Tanenbaum, M. L., Hanes, S. J., Suttiratana, S. C., Ambrosino, J. M., Ly, T. T., Maahs, D. M., Naranjo, D., Walders-Abramson, N., Weinzimer, S. A., Buckingham, B. A., Hood, K. K. 2017; 43 (2): 223-232

  Abstract

  Purpose The first hybrid closed loop (HCL) system, which automates insulin delivery but requires user inputs, was approved for treatment of type 1 diabetes (T1D) by the US Food and Drug Administration in September 2016. The purpose of this study was to explore the benefits, expectations, and attitudes of individuals with T1D following a clinical trial of an HCL system. Methods Thirty-two individuals with T1D (17 adults, 15 adolescents) participated in focus groups after 4 to 5 days of system use. Content analysis generated themes regarding perceived benefits, hassles, and limitations. Results Some participants felt misled by terms such as "closed loop" and "artificial pancreas," which seemed to imply a more "hands-off" experience. Perceived benefits were improved glycemic control, anticipated reduction of long-term complications, better quality of life, and reduced mental burden of diabetes. Hassles and limitations included unexpected tasks for the user, difficulties wearing the system, concerns about controlling highs, and being reminded of diabetes. Conclusion Users are willing to accept some hassles and limitations if they also perceive health and quality-of-life benefits beyond current self-management. It is important for clinicians to provide a balanced view of positives and negatives to help manage expectations.

  View details for DOI 10.1177/0145721717697244

  View details for PubMedID 28340542

• Prediction of acute coronary syndromes by urinary proteome analysis PLOS ONE Htun, N. M., Magliano, D. J., Zhang, Z., Lyons, J., Petit, T., Nkuipou-Kenfack, E., Ramirez-Torres, A., von zur Muhlen, C., Maahs, D., Schanstra, J. P., Pontillo, C., Pejchinovski, M., Snell-Bergeon, J. K., Delles, C., Mischak, H., Staessen, J. A., Shaw, J. E., Koeck, T., Peter, K. 2017; 12 (3)

  Abstract

  Identification of individuals who are at risk of suffering from acute coronary syndromes (ACS) may allow to introduce preventative measures. We aimed to identify ACS-related urinary peptides, that combined as a pattern can be used as prognostic biomarker. Proteomic data of 252 individuals enrolled in four prospective studies from Australia, Europe and North America were analyzed. 126 of these had suffered from ACS within a period of up to 5 years post urine sampling (cases). Proteomic analysis of 84 cases and 84 matched controls resulted in the discovery of 75 ACS-related urinary peptides. Combining these to a peptide pattern, we established a prognostic biomarker named Acute Coronary Syndrome Predictor 75 (ACSP75). ACSP75 demonstrated reasonable prognostic discrimination (c-statistic = 0.664), which was similar to Framingham risk scoring (c-statistics = 0.644) in a validation cohort of 42 cases and 42 controls. However, generating by a composite algorithm named Acute Coronary Syndrome Composite Predictor (ACSCP), combining the biomarker pattern ACSP75 with the previously established urinary proteomic biomarker CAD238 characterizing coronary artery disease as the underlying aetiology, and age as a risk factor, further improved discrimination (c-statistic = 0.751) resulting in an added prognostic value over Framingham risk scoring expressed by an integrated discrimination improvement of 0.273 ± 0.048 (P < 0.0001) and net reclassification improvement of 0.405 ± 0.113 (P = 0.0007). In conclusion, we demonstrate that urinary peptide biomarkers have the potential to predict future ACS events in asymptomatic patients. Further large scale studies are warranted to determine the role of urinary biomarkers in clinical practice.

  View details for DOI 10.1371/journal.pone.0172036

  View details for Web of Science ID 000396073700065

  View details for PubMedID 28273075

• Predictive Hyperglycemia and Hypoglycemia Minimization: In-Home Evaluation of Safety, Feasibility, and Efficacy in Overnight Glucose Control in Type 1 Diabetes. Diabetes care Spaic, T., Driscoll, M., Raghinaru, D., Buckingham, B. A., Wilson, D. M., Clinton, P., Chase, H. P., Maahs, D. M., Forlenza, G. P., Jost, E., Hramiak, I., Paul, T., Bequette, B. W., Cameron, F., Beck, R. W., Kollman, C., Lum, J. W., Ly, T. T. 2017; 40 (3): 359-366

  Abstract

  The objective of this study was to determine the safety, feasibility, and efficacy of a predictive hyperglycemia and hypoglycemia minimization (PHHM) system compared with predictive low-glucose insulin suspension (PLGS) alone in overnight glucose control.A 42-night trial was conducted in 30 individuals with type 1 diabetes in the age range 15-45 years. Participants were randomly assigned each night to either PHHM or PLGS and were blinded to the assignment. The system suspended the insulin pump on both the PHHM and PLGS nights for predicted hypoglycemia but delivered correction boluses for predicted hyperglycemia on PHHM nights only. The primary outcome was the percentage of time spent in a sensor glucose range of 70-180 mg/dL during the overnight period.The addition of automated insulin delivery with PHHM increased the time spent in the target range (70-180 mg/dL) from 71 ± 10% during PLGS nights to 78 ± 10% during PHHM nights (P < 0.001). The average morning blood glucose concentration improved from 163 ± 23 mg/dL after PLGS nights to 142 ± 18 mg/dL after PHHM nights (P < 0.001). Various sensor-measured hypoglycemic outcomes were similar on PLGS and PHHM nights. All participants completed 42 nights with no episodes of severe hypoglycemia, diabetic ketoacidosis, or other study- or device-related adverse events.The addition of a predictive hyperglycemia minimization component to our existing PLGS system was shown to be safe, feasible, and effective in overnight glucose control.

  View details for DOI 10.2337/dc16-1794

  View details for PubMedID 28100606

• Diabetes Technology and Therapy in the Pediatric Age Group. Diabetes technology & therapeutics Maahs, D. M., Shalitin, S. 2017; 19 (S1): S105-S119

  View details for DOI 10.1089/dia.2017.2510

  View details for PubMedID 28192027

• Albuminuria is associated with greater copeptin concentrations in men with type 1 diabetes: A brief report from the T1D exchange Biobank. Journal of diabetes and its complications Bjornstad, P., Johnson, R. J., Snell-Bergeon, J. K., Pyle, L., Davis, A., Foster, N., Cherney, D. Z., Maahs, D. M. 2017; 31 (2): 387-389

  Abstract

  Vasopressin exerts important cardio-renal effects, but remains problematic to measure. Copeptin is a more stable peptide derived from the same precursor molecule. In this case-control study from the Type 1 Diabetes Exchange (T1DX) Biobank registry, men with T1D and albuminuria had greater copeptin concentrations than men with normoalbuminuria.

  View details for DOI 10.1016/j.jdiacomp.2016.11.015

  View details for PubMedID 27979439

  View details for PubMedCentralID PMC5303164

• Adiponectin is associated with early diabetic kidney disease in adults with type 1 diabetes: A Coronary Artery Calcification in Type 1 Diabetes (CACTI) Study JOURNAL OF DIABETES AND ITS COMPLICATIONS Bjornstad, P., Pyle, L., Kinney, G. L., Rewers, M., Johnson, R. J., Maahs, D. M., Snell-Bergeon, J. K. 2017; 31 (2): 369-374

  View details for DOI 10.1016/j.jdiacomp.2016.06.012

  View details for Web of Science ID 000399435100013

• Predictors of Dyslipidemia Over Time in Youth With Type 1 Diabetes: For the SEARCH for Diabetes in Youth Study. Diabetes care Shah, A. S., Maahs, D. M., Stafford, J. M., Dolan, L. M., Lang, W., Imperatore, G., Bell, R. A., Liese, A. D., Reynolds, K., Pihoker, C., Marcovina, S., D'Agostino, R. B., Dabelea, D. 2017

  Abstract

  Understanding the risk factors associated with progression and regression of dyslipidemia in youth with type 1 diabetes may guide treatments.We studied 1,478 youth with type 1 diabetes (age 10.8 ± 3.9 years, 50% male, 77% non-Hispanic white, not on lipid-lowering medications) at baseline and at a mean follow-up of 7.1 ± 1.9 years in the SEARCH for Diabetes in Youth (SEARCH) study. Progression to dyslipidemia was defined as normal lipid concentrations at baseline and abnormal at follow-up (non-HDL-cholesterol [C] >130 mg/dL or HDL-C <35 mg/dL). Regression was defined as abnormal lipids at baseline and normal at follow-up. Multivariable logistic regression was used to evaluate factors associated with progression and regression compared with stable normal and stable abnormal, respectively. An area under the curve (AUC) variable was used for the time-varying covariates A1C and waist-to-height ratio (WHtR).Non-HDL-C progressed, regressed, was stable normal, and stable abnormal in 19%, 5%, 69%, and 7% of youth with type 1 diabetes, respectively. Corresponding percentages for HDL-C were 3%, 3%, 94%, and 1%, respectively. Factors associated with non-HDL-C progression were higher A1C AUC and higher WHtR AUC in males. Non-HDL-C regression was associated with lower WHtR AUC, and HDL-C progression was associated with male sex and higher WHtR AUC. HDL-C regression was not modeled due to small numbers.A1C and WHtR are modifiable risk factors associated with change in dyslipidemia over time in youth with type 1 diabetes.

  View details for DOI 10.2337/dc16-2193

  View details for PubMedID 28126715

  View details for PubMedCentralID PMC5360282

• Obesity and type 2 diabetes are associated with elevated PCSK9 levels in young women. Pediatric diabetes Levenson, A. E., Shah, A. S., Khoury, P. R., Kimball, T. R., Urbina, E. M., de Ferranti, S. D., Maahs, D. M., Dolan, L. M., Wadwa, R. P., Biddinger, S. B. 2017

  Abstract

  Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a key regulator of low-density lipoprotein cholesterol and cardiovascular disease risk, and is an emerging therapeutic target.We compared serum PCSK9 levels in young adults, with and without type 2 diabetes.Cross-sectional analysis was conducted in a cohort, aged 15 to 26?years, in Cincinnati, OH, from 2005 to 2010. Serum PCSK9 levels were measured in 94 youth with type 2 diabetes, 93 obese control subjects, and 99 lean control subjects. Correlative analyses were conducted to determine significant covariates of PCSK9 by group and sex, and multivariate linear regression models were used to study the independent determinants of PCSK9.In females, PCSK9 levels were significantly increased in the obese and type 2 diabetes subjects relative to the lean controls (P?

  View details for DOI 10.1111/pedi.12490

  View details for PubMedID 28093849

• Obese adolescents with polycystic ovarian syndrome have elevated cardiovascular disease risk markers. Vascular medicine Patel, S. S., Truong, U., King, M., Ferland, A., Moreau, K. L., Dorosz, J., Hokanson, J. E., Wang, H., Kinney, G. L., Maahs, D. M., Eckel, R. H., Nadeau, K. J., Cree-Green, M. 2017: 1358863X16682107-?

  Abstract

  Women with polycystic ovarian syndrome (PCOS) have evidence of subclinical cardiovascular disease (CVD). However, insulin resistance, an important factor in the development of CVD in adults, is common in adolescents with PCOS, yet data in adolescents are limited. Therefore, we sought to measure insulin resistance and CVD markers in obese youth with and without PCOS. Thirty-six PCOS and 17 non-PCOS adolescent girls who were obese, sedentary, and non-hypertensive were recruited from clinics located within the Children's Hospital Colorado. Following 3 days of controlled diet and restricted exercise, fasting plasma samples were obtained prior to a hyperinsulinemic euglycemic clamp. PCOS girls were more insulin resistant than controls (glucose infusion rate 5.24±1.86 mg/kg/min vs 9.10±2.69; p<0.001). Girls with PCOS had blood pressure in the normal range, but had greater carotid intima-media thickness (cIMT) (0.49±0.07 mm vs 0.44±0.06; p=0.038), beta stiffness index (5.1±1.3 U vs 4.4±0.9; p=0.037), and reduced arterial compliance (1.95±0.47 mm(2)/mmHg × 10(-1) vs 2.13±0.43; p=0.047). PCOS girls had a normal mean lipid profile, yet had a more atherogenic lipoprotein cholesterol distribution and had persistent elevations of free fatty acids despite hyperinsulinemia (68±28 ?mol/mL vs 41±10; p=0.001), both potential contributors to CVD. Free fatty acid concentrations correlated best with all CVD markers. In summary, adolescent girls with PCOS have greater cIMT and stiffer arteries than girls without PCOS, perhaps related to altered lipid metabolism, even when clinical measures of blood pressure and cholesterol profiles are 'normal'. Therefore, management of adolescent PCOS should include assessment of CVD risk factor development.

  View details for DOI 10.1177/1358863X16682107

  View details for PubMedID 28095749

• Response to Comment on Hofer et al. International Comparison of Smoking and Metabolic Control in Patients With Type 1 Diabetes. Diabetes Care 2016;39:e177-e178. Diabetes care Hofer, S. E., Miller, K., Hermann, J. M., DeSalvo, D. J., Riedl, M., Hirsch, I. B., Karges, W., Beck, R. W., Holl, R. W., Maahs, D. M. 2017; 40 (3): e37

  View details for PubMedID 28223449

• PCSK9 Is Increased in Youth With Type 1 Diabetes. Diabetes care Levenson, A. E., Wadwa, R. P., Shah, A. S., Khoury, P. R., Kimball, T. R., Urbina, E. M., de Ferranti, S. D., Bishop, F. K., Maahs, D. M., Dolan, L. M., Biddinger, S. B. 2017; 40 (7): e85?e87

  View details for PubMedID 28588146

  View details for PubMedCentralID PMC5481981

• Use of Adjuvant Pharmacotherapy in Type 1 Diabetes: International Comparison of 49,996 Individuals in the Prospective Diabetes Follow-up and T1D Exchange Registries. Diabetes care Lyons, S. K., Hermann, J. M., Miller, K. M., Hofer, S. E., Foster, N. C., Rami-Merhar, B. M., Aleppo, G., Seufert, J., DiMeglio, L. A., Danne, T., Maahs, D. M., Holl, R. W. 2017; 40 (10): e139?e140

  View details for PubMedID 28768688

• Response to Comment on Craig et al. Prevalence of Celiac Disease in 52,721 Youth With Type 1 Diabetes: International Comparison Across Three Continents. Diabetes Care 2017;40:1034-1040. Diabetes care Craig, M. E., Prinz, N., Boyle, C. T., Campbell, F. M., Jones, T. W., Hofer, S. E., Simmons, J. H., Holman, N., Tham, E., Fröhlich-Reiterer, E., DuBose, S., Thornton, H., King, B., Maahs, D. M., Holl, R. W., Warner, J. T. 2017; 40 (11): e168?e169

  View details for PubMedID 29061596

• In-Home Closed Loop Control for Artificial Pancreas: Patient and Provider Perspective DIABETES TECHNOLOGY & THERAPEUTICS Ekhlaspour, L., Maahs, D. M. 2017; 19 (1): 4?6

  View details for PubMedID 28055224

• Biopsychosocial Aspects of Weight Management in Type 1 Diabetes: a Review and Next Steps. Current diabetes reports Driscoll, K. A., Corbin, K. D., Maahs, D. M., Pratley, R., Bishop, F. K., Kahkoska, A., Hood, K. K., Mayer-Davis, E. 2017; 17 (8): 58

  Abstract

  This review aims to summarize the type 1 diabetes (T1D) and weight literature with an emphasis on barriers associated with weight management, the unique T1D-specific factors that impact weight loss success, maladaptive and adaptive strategies for weight loss, and interventions to promote weight loss.Weight gain is associated with intensive insulin therapy. Overweight and obese weight status in individuals with T1D is higher than the general population and prevalence is rising. A variety of demographic (e.g., female sex), clinical (e.g., greater insulin needs), environmental (e.g., skipping meals), and psychosocial (e.g., depression, stress) factors are associated with overweight/obese weight status in T1D. Fear of hypoglycemia is a significant barrier to engagement in physical activity. Studies evaluating adaptive weight loss strategies in people with T1D are limited. There is a growing literature highlighting the prevalence and seriousness of overweight and obesity among both youth and adults with T1D. There is an urgent need to develop evidence-based weight management guidelines and interventions that address the unique concerns of individuals with T1D and that concurrently address glycemic control.

  View details for PubMedID 28660565

• Serum cystatin C in youth with diabetes: The SEARCH for diabetes in youth study. Diabetes research and clinical practice Kanakatti Shankar, R., Dolan, L. M., Isom, S., Saydah, S., Maahs, D. M., Dabelea, D., Reynolds, K., Hirsch, I. B., Rodriguez, B. L., Mayer-Davis, E. J., Marcovina, S., D'Agostino, R., Mauer, M., Mottl, A. K. 2017; 130: 258?65

  Abstract

  We compared cystatin C in youth with versus without diabetes and determined factors associated with cystatin C in youth with type 1 diabetes (T1D) and type 2 diabetes (T2D).Youth (ages 12-19years) without diabetes (N=544) were ascertained from the NHANES Study 2000-2002 and those with T1D (N=977) and T2D (N=168) from the SEARCH for Diabetes in Youth Study. Adjusted means of cystatin C concentrations were compared amongst the 3 groups. Next, we performed multivariable analyses within the T1D and T2D SEARCH samples to determine the association between cystatin C and race, sex, age, diabetes duration, HbA1c, fasting glucose, and BMI.Adjusted cystatin C concentrations were statistically higher in NHANES (0.85mg/L) than in either the T1D (0.75mg/L) or T2D (0.70mg/L) SEARCH groups (P<0.0001). Fasting glucose was inversely related to cystatin C only in T1D (P<0.001) and BMI positively associated only in T2D (P<0.01) while HbA1c was inversely associated in both groups.Cystatin C concentrations are statistically higher in youth without diabetes compared to T1D or T2D, however the clinical relevance of this difference is quite small, especially in T1D. In youth with diabetes, cystatin C varies with BMI and acute and chronic glycemic control, however their effects may be different according to diabetes type.

  View details for PubMedID 28666182

  View details for PubMedCentralID PMC5575920

• Closed-Loop Control Without Meal Announcement in Type 1 Diabetes. Diabetes technology & therapeutics Cameron, F. M., Ly, T. T., Buckingham, B. A., Maahs, D. M., Forlenza, G. P., Levy, C. J., Lam, D., Clinton, P., Messer, L. H., Westfall, E., Levister, C., Xie, Y. Y., Baysal, N., Howsmon, D., Patek, S. D., Bequette, B. W. 2017; 19 (9): 527?32

  Abstract

  A fully closed-loop insulin-only system was developed to provide glucose control in patients with type 1 diabetes without requiring announcement of meals or activity. Our goal was to assess initial safety and efficacy of this system.The multiple model probabilistic controller (MMPPC) anticipates meals when the patient is awake. The controller used the subject's basal rates and total daily insulin dose for initialization. The system was tested at two sites on 10 patients in a 30-h inpatient study, followed by 15 subjects at three sites in a 54-h supervised hotel study, where the controller was challenged by exercise and unannounced meals. The system was implemented on the UVA DiAs system using a Roche Spirit Combo Insulin Pump and a Dexcom G4 Continuous Glucose Monitor.The mean overall (24-h basis) and nighttime (11 PM-7 AM) continuous glucose monitoring (CGM) values were 142 and 125?mg/dL during the inpatient study. The hotel study used a different daytime tuning and manual announcement, instead of automatic detection, of sleep and wake periods. This resulted in mean overall (24-h basis) and nighttime CGM values of 152 and 139?mg/dL for the hotel study and there was also a reduction in hypoglycemia events from 1.6 to 0.91 events/patient/day.The MMPPC system achieved a mean glucose that would be particularly helpful for people with an elevated A1c as a result of frequent missed meal boluses. Current full closed loop has a higher risk for hypoglycemia when compared with algorithms using meal announcement.

  View details for PubMedID 28767276

  View details for PubMedCentralID PMC5647490

• Predictors of early renal function decline in adults with Type 1 diabetes: the Coronary Artery Calcification in Type 1 Diabetes and the Pittsburgh Epidemiology of Diabetes Complications studies. Diabetic medicine : a journal of the British Diabetic Association Bjornstad, P., Costacou, T., Miller, R. G., Maahs, D. M., Rewers, M. J., Orchard, T. J., Snell-Bergeon, J. K. 2017; 34 (11): 1532?40

  Abstract

  Diabetic kidney disease is one of the leading complications of Type 1 diabetes, but its prediction remains a challenge. We examined predictors of rapid decline in estimated GFR (eGFR) in two Type 1 diabetes cohorts: the Coronary Artery Calcification in Type 1 Diabetes (CACTI) and the Pittsburgh Epidemiology of Diabetes Complications (EDC).A select subset of participants (CACTI: n = 210 and EDC: n = 98) diagnosed before 17 years of age with Type 1 diabetes duration ? 7 years, and follow-up data on eGFR by CKD-EPI creatinine for up to 8 years were included in the analyses. Early renal function decline was defined as annual decline in eGFR ? 3 ml/min/1.73 m2, and normal age-related decline as eGFR ? 1 ml/min/1.73 m2. Parallel logistic regression models were constructed in the two cohorts.Early renal function decline incidence was 36% in CACTI and 41% in EDC. In both cohorts, greater baseline eGFR (CACTI: OR 3.12, 95% CI 1.97-5.05; EDC: OR 1.92, 95% CI 1.17-3.15 per 10 ml/min/1.73 m2) and log albumin-to-creatinine (ACR) (CACTI: OR 3.24, 95% CI 1.80-5.83; EDC: OR 1.87, 95% CI 1.18-2.96 per 1 unit) predicted greater odds of early renal function decline in fully adjusted models. Conversely, ACE inhibition predicted lower odds of early renal function decline in women in CACTI, but similar relationships were not observed in women in EDC.A substantial proportion of people with Type 1 diabetes in the EDC and CACTI cohorts experienced early renal function decline over time. ACE inhibition appeared to be protective only in women in CACTI where the prevalence of its use was twofold higher compared with the EDC.

  View details for DOI 10.1111/dme.13430

  View details for PubMedID 28734104

  View details for PubMedCentralID PMC5647234

• Behavioural implications of traditional treatment and closed-loop automated insulin delivery systems in Type 1 diabetes: applying a cognitive restraint theory framework. Diabetic medicine : a journal of the British Diabetic Association Kahkoska, A. R., Mayer-Davis, E. J., Hood, K. K., Maahs, D. M., Burger, K. S. 2017; 34 (11): 1500?1507

  Abstract

  As the prevalence of obesity in Type 1 diabetes rises, the effects of emerging therapy options should be considered in the context of both weight and glycaemic control outcomes. Artificial pancreas device systems will 'close the loop' between blood glucose monitoring and automated insulin delivery and may transform day-to-day dietary management for people with Type 1 diabetes in multiple ways. In the present review, we draw directly from cognitive restraint theory to consider unintended impacts that closed-loop systems may have on ingestive behaviour and food intake. We provide a brief overview of dietary restraint theory and its relation to weight status in the general population, discuss the role of restraint in traditional Type 1 diabetes treatment, and lastly, use this restraint framework to discuss the possible behavioural implications and opportunities of closed-loop systems in the treatment of Type 1 diabetes. We hypothesize that adopting closed-loop systems will lift the diligence and restriction that characterizes Type 1 diabetes today, thus requiring a transition from a restrained eating behaviour to a non-restrained eating behaviour. Furthermore, we suggest this transition be leveraged as an opportunity to teach people lifelong eating behaviour to promote healthy weight status by incorporating education and cognitive reappraisal. Our aim was to use a transdisciplinary approach to highlight critical aspects of the emerging closed-loop technologies relating to eating behaviour and weight effects and to promote discussion of strategies to optimize long-term health in Type 1 diabetes via two key outcomes: glycaemic control and weight management.

  View details for DOI 10.1111/dme.13407

  View details for PubMedID 28626906

  View details for PubMedCentralID PMC5647213

• Implementation of Depression Screening and Global Health Assessment in Pediatric Subspecialty Clinics. The Journal of adolescent health : official publication of the Society for Adolescent Medicine Iturralde, E., Adams, R. N., Barley, R. C., Bensen, R., Christofferson, M., Hanes, S. J., Maahs, D. M., Milla, C., Naranjo, D., Shah, A. C., Tanenbaum, M. L., Veeravalli, S., Park, K. T., Hood, K. K. 2017

  Abstract

  Adolescents with chronic illness face greater risk of psychosocial difficulties, complicating disease management. Despite increased calls to screen for patient-reported outcomes, clinical implementation has lagged. Using quality improvement methods, this study aimed to investigate the feasibility of standardized screening for depression and assessment of global health and to determine recommended behavioral health follow-up, across three pediatric subspecialty clinics.A total of 109 patients aged 12-22 years (median = 16.6) who were attending outpatient visits for treatment of diabetes (80% type 1), inflammatory bowel disease, or cystic fibrosis completed the 9-item Patient Health Questionnaire (PHQ-9) depression and Patient-Reported Outcomes Measurement Information System (PROMIS) Pediatric Global Health measures on electronic tablets. Patients screening positive on the PHQ-9 received same-day behavioral health assessment and regular phone check-ins to facilitate necessary follow-up care.Overall, 89% of 122 identified patients completed screening during a 6-month window. Patients completed measures in a timely manner (within 3 minutes) without disruption to clinic flow, and they rated the process as easy, comfortable, and valuable. Depression scores varied across disease type. Patients rated lower global health relative to a previously assessed validation cohort. Depression and global health related significantly to certain medical outcomes. Fifteen percent of patients screened positive on the PHQ-9, of whom 50% confirmed attending behavioral health appointments within 6 months of screening.A standardized depression and global health assessment protocol implemented across pediatric subspecialties was feasible and effective. Universal behavioral health screening for adolescents and young adults living with chronic disease is necessary to meet programmatic needs in pediatric subspecialty clinics.

  View details for PubMedID 28830798

• Closed-Loop Control During Intense Prolonged Outdoor Exercise in Adolescents With Type 1 Diabetes: The Artificial Pancreas Ski Study. Diabetes care Breton, M. D., Cherñavvsky, D. R., Forlenza, G. P., DeBoer, M. D., Robic, J., Wadwa, R. P., Messer, L. H., Kovatchev, B. P., Maahs, D. M. 2017; 40 (12): 1644?50

  Abstract

  Intense exercise is a major challenge to the management of type 1 diabetes (T1D). Closed-loop control (CLC) systems (artificial pancreas) improve glycemic control during limited intensity and short duration of physical activity (PA). However, CLC has not been tested during extended vigorous outdoor exercise common among adolescents.Skiing presents unique metabolic challenges: intense prolonged PA, cold, altitude, and stress/fear/excitement. In a randomized controlled trial, 32 adolescents with T1D (ages 10-16 years) participated in a 5-day ski camp (?5 h skiing/day) at two sites: Wintergreen, VA, and Breckenridge, CO. Participants were randomized to the University of Virginia CLC system or remotely monitored sensor-augmented pump (RM-SAP). The CLC and RM-SAP groups were coarsely paired by age and hemoglobin A1c(HbA1c). All subjects were remotely monitored 24 h per day by the study physicians and clinical team.Compared with physician-monitored open loop, percent time in range (70-180 mg/dL) improved using CLC: 71.3 vs. 64.7% (+6.6% [95% CI 1-12];P= 0.005), with maximum effect late at night. Hypoglycemia exposure and carbohydrate treatments were improved overall (P= 0.001 andP= 0.007) and during the daytime with strong ski level effects (P= 0.0001 andP= 0.006); ski/snowboard proficiency was balanced between groups but with a very strong site effect: naive in Virginia and experienced in Colorado. There was no adverse event associated with CLC; the participants' feedback was overwhelmingly positive.CLC in adolescents with T1D improved glycemic control and reduced exposure to hypoglycemia during prolonged intensive winter sport activities, despite the added challenges of cold and altitude.

  View details for PubMedID 28855239

  View details for PubMedCentralID PMC5711335

• International Consensus on Use of Continuous Glucose Monitoring. Diabetes care Danne, T., Nimri, R., Battelino, T., Bergenstal, R. M., Close, K. L., DeVries, J. H., Garg, S., Heinemann, L., Hirsch, I., Amiel, S. A., Beck, R., Bosi, E., Buckingham, B., Cobelli, C., Dassau, E., Doyle, F. J., Heller, S., Hovorka, R., Jia, W., Jones, T., Kordonouri, O., Kovatchev, B., Kowalski, A., Laffel, L., Maahs, D., Murphy, H. R., Nørgaard, K., Parkin, C. G., Renard, E., Saboo, B., Scharf, M., Tamborlane, W. V., Weinzimer, S. A., Phillip, M. 2017; 40 (12): 1631?40

  Abstract

  Measurement of glycated hemoglobin (HbA1c) has been the traditional method for assessing glycemic control. However, it does not reflect intra- and interday glycemic excursions that may lead to acute events (such as hypoglycemia) or postprandial hyperglycemia, which have been linked to both microvascular and macrovascular complications. Continuous glucose monitoring (CGM), either from real-time use (rtCGM) or intermittently viewed (iCGM), addresses many of the limitations inherent in HbA1ctesting and self-monitoring of blood glucose. Although both provide the means to move beyond the HbA1cmeasurement as the sole marker of glycemic control, standardized metrics for analyzing CGM data are lacking. Moreover, clear criteria for matching people with diabetes to the most appropriate glucose monitoring methodologies, as well as standardized advice about how best to use the new information they provide, have yet to be established. In February 2017, the Advanced Technologies & Treatments for Diabetes (ATTD) Congress convened an international panel of physicians, researchers, and individuals with diabetes who are expert in CGM technologies to address these issues. This article summarizes the ATTD consensus recommendations and represents the current understanding of how CGM results can affect outcomes.

  View details for PubMedID 29162583

• Reported gastroparesis in adults with type 1 diabetes (T1D) from the T1D Exchange clinic registry. Journal of diabetes and its complications Aleppo, G., Calhoun, P., Foster, N. C., Maahs, D. M., Shah, V. N., Miller, K. M. 2017; 31 (12): 1669?73

  Abstract

  To better understand the prevalence and impact of gastroparesis in the T1D Exchange clinic registry database.The analysis included 7107 adult participants with T1D across 45 sites (median age 46years. and median duration 24years). Linear and logistic regression models were used to assess the association of gastroparesis vs. no gastroparesis (obtained from medical record) with demographic characteristics, glycemic control and diabetes complications.Among 7107 registry participants, 340 (4.8%) had a clinical diagnosis of gastroparesis. Females were more likely to have gastroparesis compared with males (5.8% vs. 3.5%, P<0.001). Participants with gastroparesis compared with those without gastroparesis were older (median age 49.4 vs. 45.3years, P<0.001), had a longer duration of T1D (median duration 32 vs. 23years, P<0.001), higher mean HbA1c (8.1% vs. 7.7% [65 vs. 61mmol/mol], P<0.001), more frequent severe hypoglycemia (25% vs. 11% with ?1 event in the past 12months, P<0.001), lower socio-economic status, less likely to be using CGM and insulin pump and greater prevalence of microvascular and neuropathic complications than participants without gastroparesis.Gastroparesis is associated with higher risk of severe hypoglycemia despite higher HbA1c levels than in T1D patients without gastroparesis. The increased presence of multiple long-term complications and overall poor glycemic control in these subjects emphasizes the need to establish diagnostic protocols for earlier diagnosis, achieve tighter glycemic control with more extensive use of insulin pumps and continuous glucose monitoring, and the need for wider availability of medical therapies for treatment of diabetic gastroparesis.

  View details for PubMedID 28989086

• Continuous Glucose Monitoring Enables the Detection of Losses in Infusion Set Actuation (LISAs) SENSORS Howsmon, D. P., Cameron, F., Baysal, N., Ly, T. T., Forlenza, G. P., Maahs, D. M., Buckingham, B. A., Hahn, J., Bequette, B. W. 2017; 17 (1)

  Abstract

  Reliable continuous glucose monitoring (CGM) enables a variety of advanced technology for the treatment of type 1 diabetes. In addition to artificial pancreas algorithms that use CGM to automate continuous subcutaneous insulin infusion (CSII), CGM can also inform fault detection algorithms that alert patients to problems in CGM or CSII. Losses in infusion set actuation (LISAs) can adversely affect clinical outcomes, resulting in hyperglycemia due to impaired insulin delivery. Prolonged hyperglycemia may lead to diabetic ketoacidosis-a serious metabolic complication in type 1 diabetes. Therefore, an algorithm for the detection of LISAs based on CGM and CSII signals was developed to improve patient safety. The LISA detection algorithm is trained retrospectively on data from 62 infusion set insertions from 20 patients. The algorithm collects glucose and insulin data, and computes relevant fault metrics over two different sliding windows; an alarm sounds when these fault metrics are exceeded. With the chosen algorithm parameters, the LISA detection strategy achieved a sensitivity of 71.8% and issued 0.28 false positives per day on the training data. Validation on two independent data sets confirmed that similar performance is seen on data that was not used for training. The developed algorithm is able to effectively alert patients to possible infusion set failures in open-loop scenarios, with limited evidence of its extension to closed-loop scenarios.

  View details for DOI 10.3390/s17010161

  View details for Web of Science ID 000393021000160

  View details for PubMedID 28098839

  View details for PubMedCentralID PMC5298734

• Algorithms for a Single Hormone Closed-Loop Artificial Pancreas: Challenges Pertinent to Chemical Process Operations and Control PROCESSES Bequette, B., Cameron, F., Baysal, N., Howsmon, D. P., Buckingham, B. A., Maahs, D. M., Levy, C. J. 2016; 4 (4)

  Abstract

  The development of a closed-loop artificial pancreas to regulate the blood glucose concentration of individuals with type 1 diabetes has been a focused area of research for over 50 years, with rapid progress during the past decade. The daily control challenges faced by someone with type 1 diabetes include asymmetric objectives and risks, and one-sided manipulated input action with frequent relatively fast disturbances. The major automation steps toward a closed-loop artificial pancreas include (i) monitoring and overnight alarms for hypoglycemia (low blood glucose); (ii) overnight low glucose suspend (LGS) systems to prevent hypoglycemia; and (iii) fully closed-loop systems that adjust insulin (and perhaps glucagon) to maintain desired blood glucose levels day and night. We focus on the steps that we used to develop and test a probabilistic, risk-based, model predictive control strategy for a fully closed-loop artificial pancreas. We complete the paper by discussing ramifications of lessons learned for chemical process systems applications.

  View details for PubMedID 30740333

• Ambulatory glucose profile analysis of the juvenile diabetes research foundation continuous glucose monitoring dataset-Applications to the pediatric diabetes population. Pediatric diabetes Forlenza, G. P., Pyle, L. L., Maahs, D. M., Dunn, T. C. 2016

  Abstract

  Increased continuous glucose monitor (CGM) use presents both the benefit and burden of increased data for clinicians to rapidly analyze. The ambulatory glucose profile (AGP) is an evolving a universal software report for CGM data analysis.We utilized the Juvenile Diabetes Research Foundation-CGM dataset to evaluate the AGP across a broad spectrum of patients to show how AGP can be used clinically to assist with CGM-related decision making. We hypothesized that AGP metrics would be different across age and HbA1c strata.AGPs were generated from the JDRF-CGM trial dataset for all periods during which there were ?10?days of CGM coverage in the 2 weeks adjacent to an HbA1c measurement yielding 1101 AGPs for 393 unique subjects.AGPs were stratified by age group (8-14, 15-24, and ?25?years) and HbA1c (within or above target for age) and compared for between group differences in AGP metrics via two-factor ANOVA. Glycemic differences between time periods were analyzed via segmented regression analysis.Glucose exposure (average and estimated A1c) and variability (standard deviation and interquartile range) were different between the low and high HbA1c levels. Within a given HbA1c level all age groups were significantly different from each other with older patients having lower averages with less variability than younger patients.AGP analysis of the JDRF-CGM data highlights significant differences in glycemic profiles between pediatric and adult age groups and between well and less well-controlled patient populations.

  View details for DOI 10.1111/pedi.12474

  View details for PubMedID 27878929

• Severe hypoglycemia rates are not associated with HbA1c: a cross-sectional analysis of 3 contemporary pediatric diabetes registry databases. Pediatric diabetes Haynes, A., Hermann, J. M., Miller, K. M., Hofer, S. E., Jones, T. W., Beck, R. W., Maahs, D. M., Davis, E. A., Holl, R. W. 2016

  Abstract

  To examine the association between glycated hemoglobin (HbA1c) and severe hypoglycemia rates in patients with type 1 diabetes receiving usual care, by analysing data from the US Type 1 Diabetes Exchange (T1DX), German/Austrian Diabetes Patienten Verlaufsdokumenation (DPV), and Western Australian Children Diabetes Database (WACDD) diabetes registries.Data for patients with type 1 diabetes, aged <18 years with a minimum duration of diabetes of 2 years, were extracted from each registry for a 12-month observation period between 2011 and 2012 (7,102 T1DX, 18,887 DPV, and 865 WACDD). Rates of severe hypoglycemia (self-reported loss of consciousness/convulsion) were estimated per 100 patient-years and analyzed by HbA1c, source registry, treatment regimen, and age group.Overall, the severe hypoglycemia rate per 100 patient years was 7.1, 3.3, and 6.7 in T1DX, DPV, and WACDD patients, respectively. Lower HbA1c was not associated with an increased rate of severe hypoglycemia when examined by source registry, treatment regimen, or age group.An inverse relationship between mean HbA1c and risk of severe hypoglycemia was not observed in this study of 3, independent cohorts of children and adolescents with type 1 diabetes. Investigation in other large, longitudinal cohorts is recommended to further characterize the contemporary relationship between glycemic control and risk of severe hypoglycemia rates in pediatric patients with type 1 diabetes.

  View details for DOI 10.1111/pedi.12477

  View details for PubMedID 27878914

• Characteristics of youth with type 1 diabetes (T1D) with and without a parent with T1D in the T1D exchange clinic registry. Journal of diabetes Fox, L. A., Mubasher, M., Wolfsdorf, J. I., Buckingham, B. A., Peters, A. L., Tamborlane, W. V., Schatz, D. A., Maahs, D. M., Miller, K. M., Beck, R. W. 2016; 8 (6): 834-838

  Abstract

  The aim of the present study was to compare characteristics and diabetes management in children and adolescents with and without at least one parent with type 1 diabetes (T1D).In all, 12 890 participants aged <18?years at enrollment in the T1D Exchange Registry were included in the present study. Statistical comparisons between those with and without parental T1D were conducted using a univariate generalized linear mixed model.Of the study participants, 1056 (8.2%) registrants had at least one parent with T1D. Those with parental T1D were slightly, albeit significantly, younger (6.3 vs 6.9?years; P?< 0.001) and less likely to have diabetic ketoacidosis (DKA) at diagnosis (24% vs 41%; P?< 0.001) than those without parental T1D. There were no differences between groups in HbA1c, use of continuous glucose monitoring or insulin pump therapy, or the development of severe hypoglycemia or DKA. In addition, there were no differences found when comparing characteristics or diabetes management in those with a mother versus those with a father with T1D.Children and adolescents with parental T1D tend to be diagnosed earlier. Diabetes management, glycemic control, and acute complications are similar in those with and without parental T1D.

  View details for DOI 10.1111/1753-0407.12363

  View details for PubMedID 26663683

• The Gomez equations and renal hemodynamic function in kidney disease research AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY Bjornstad, P., Skrtic, M., Lytvyn, Y., Maahs, D. M., Johnson, R. J., Cherney, D. Z. 2016; 311 (5): F967-F975

  View details for DOI 10.1152/ajprenal.00415.2016

  View details for Web of Science ID 000389646700016

• Efficacy of an Overnight Predictive Low-Glucose Suspend System in Relation to Hypoglycemia Risk Factors in Youth and Adults With Type 1 Diabetes. Journal of diabetes science and technology Calhoun, P. M., Buckingham, B. A., Maahs, D. M., Hramiak, I., Wilson, D. M., Aye, T., Clinton, P., Chase, P., Messer, L., Kollman, C., Beck, R. W., Lum, J. 2016; 10 (6): 1216-1221

  Abstract

  We developed a system to suspend insulin pump delivery overnight when the glucose trend predicts hypoglycemia. This predictive low-glucose suspend (PLGS) system substantially reduces nocturnal hypoglycemia without an increase in morning ketosis. Evaluation of hypoglycemia risk factors that could potentially influence the efficacy of the system remains critical for understanding possible problems with the system and identifying patients that may have the greatest benefit when using the system.The at-home randomized trial consisted of 127 study participants with hemoglobin A1c (A1C) of ?8.5% (mmol/mol) for patients aged 4-14 years and ?8.0% for patient aged 15-45 years. Factors assessed included age, gender, A1C, diabetes duration, daily percentage basal insulin, total daily dose of insulin (units/kg-day), bedtime BG, bedtime snack, insulin on board, continuous glucose monitor (CGM) rate of change (ROC), day of the week, time system activated, daytime exercise intensity, and daytime CGM-measured hypoglycemia.The PLGS system was effective in preventing hypoglycemia for each factor subgroup. There was no evidence that the PLGS system was more or less effective in preventing hypoglycemia in any one subgroup compared with the other subgroups based on that factor. In addition, the effect of the system on overnight hyperglycemia did not differ in subgroups.The PLGS system tested in this study effectively reduced hypoglycemia without a meaningful increase in hyperglycemia across a variety of factors.

  View details for PubMedID 27207890

• Early Detection of Infusion Set Failure During Insulin Pump Therapy in Type 1 Diabetes. Journal of diabetes science and technology Cescon, M., DeSalvo, D. J., Ly, T. T., Maahs, D. M., Messer, L. H., Buckingham, B. A., Doyle, F. J., Dassau, E. 2016; 10 (6): 1268-1276

  Abstract

  Insulin infusion set failure resulting in prolonged hyperglycemia or diabetic ketoacidosis can occur with pump therapy in type 1 diabetes. Set failures are frequently characterized by variable and unpredictable patterns of increasing glucose values despite increased insulin infusion. Early detection may minimize the risk of prolonged hyperglycemia, an important consideration for automated insulin delivery and closed-loop applications.A novel algorithm designed to alert the patient to the onset of infusion set failure was developed based upon continuous glucose sensor values and insulin delivered from an insulin pump. The method was calibrated on 12 weeks of infusion set wear without failures recorded by 4 patients in ambulatory conditions and prospectively validated on 18 weeks of infusion set wear with and without failures belonging to 9 other subjects in ambulatory conditions.The algorithm, evaluated retrospectively, identified a failure 2.52 ± 1.91 days ahead of the actual event as recorded by the clinical team, corresponding to 50% sensitivity, 66% specificity and 55% accuracy. If set failure alarms had been activated in real time, the average time >180 mg/dl would be reduced from 82.7 ± 40.9 hours/week/subject (without alarm) to 58.8 ± 31.1 hours/week/subject (with alarm), corresponding to a potential 29% reduction in time spent >180mg/dl.The proposed method for early detection of infusion set failure based on glucose sensor and insulin data demonstrated favorable results on retrospective data and may be implemented as an additional safeguard in a future fully automated closed-loop system.

  View details for PubMedID 27621142

• A survey of youth with new onset type 1 diabetes: Opportunities to reduce diabetic ketoacidosis. Pediatric diabetes Baldelli, L., Flitter, B., Pyle, L., Maahs, D. M., Klingensmith, G., Slover, R., Alonso, G. T. 2016

  Abstract

  Pediatric patients in Colorado with new onset type 1 diabetes (T1D) presenting with diabetic ketoacidosis (DKA) increased from 29.9% to 46.2% from 1998 to 2012. The purpose of this study was to compare differences between patients with newly diagnosed T1D who presented in DKA with those who did not across three domains: sociodemographic factors, access to medical care, and medical provider factors, aiming to identify potential targets for intervention.Sixty-one patients <17 years of age with T1D duration <6 months completed the questionnaire. Groups were compared using Fisher's exact test or the Kruskal-Wallis test.Parents of 28% of patients researched their child's symptoms on the Internet prior to diagnosis. At the first healthcare visit for symptoms of T1D, 23% were not diagnosed. There were no significant differences between groups (DKA vs non-DKA) in demographics, first healthcare setting for T1D symptoms, provider type at first visit or at diagnosis, insurance status, or specific barriers to care. DKA patients had a longer interval between previous well visit to diagnosis (median 172 vs 263 days, P = 0.01). Non-DKA patients were more likely to have blood glucose measured at P = 0.02, and had fewer symptoms prior to (P = 0.01) the first visit for diabetes symptoms. Parents of non-DKA patients were more likely to be familiar with symptoms of diabetes (P < 0.001) and to suspect diabetes (P = 0.01).Targets for campaigns to prevent DKA include increasing provider glucose and ketone testing, increasing public knowledge about diabetes, and understanding how socio-demographic factors may delay T1D diagnosis.

  View details for DOI 10.1111/pedi.12455

  View details for PubMedID 27726268

• Type 1 diabetes in older adults: Comparing treatments and chronic complications in the United States T1D Exchange and the German/Austrian DPV registries. Diabetes research and clinical practice Weinstock, R. S., Schütz-Fuhrmann, I., Connor, C. G., Hermann, J. M., Maahs, D. M., Schütt, M., Agarwal, S., Hofer, S. E., Beck, R. W., Holl, R. W. 2016; 122: 28-37

  Abstract

  Compare characteristics, therapies and clinical outcomes in older adults with type 1 diabetes in the United States T1D Exchange (T1DX) and German/Austrian Diabetes Patienten Verlaufsdokumentation (DPV) registries.Cross-sectional study of adults ?60years old with type 1 diabetes seen in 2011-2012 in the T1DX (n=1283) and DPV (n=2014) registries. Wilcoxon rank-sum test was used for continuous variables and chi-square test for categorical variables. Adjusted analyses used generalized linear models.Individuals in both registries were similar in body mass index (mean 27kg/m(2)), percent with obesity (25%) and gender (48% male). In T1DX there was longer diabetes duration (32.3 vs. 28.8years), greater use of antihypertensive medications (including ACE-I and ARBs; 85% vs. 62%), statins (68% vs. 40%), aspirin (77% vs. 21%), insulin pumps (58% vs. 18%), and less smoking (7% vs. 10%); lower adjusted mean LDL-cholesterol (84 vs. 109mg/dL), and lower adjusted mean systolic and diastolic blood pressures (128 vs. 136 and 68 vs. 74mmHg); fewer myocardial infarctions (6% vs. 9% [99% CI of difference, 1% to 5%]), strokes (2% vs. 8% [3% to 7%]), microvascular complications including microalbuminuria (17% vs. 44% [22% to 32%]) but increased depression (16.1% vs. 8.7%). Adjusted mean HbA1c levels were similar (7.5%, 58mmol/mol).Differences between the registries included greater use of antihypertensives, statins and insulin pumps, and fewer chronic complications in the T1DX. Further research is needed to better understand the role of intensive therapy in improving outcomes in older adults with type 1 diabetes.

  View details for DOI 10.1016/j.diabres.2016.09.024

  View details for PubMedID 27764721

• Insulin pump therapy in children with type 1 diabetes: analysis of data from the SWEET registry PEDIATRIC DIABETES Szypowska, A., Schwandt, A., Svensson, J., Shalitin, S., Cardona-Hernandez, R., Forsander, G., Sundberg, F., De Beaufort, C., Maahs, D., Maffeis, C., O'Riordan, S. M., Krisane, I. D., Scharf, M., Castro, S., Konstantinova, M., Obermannova, B., Casteels, K., Goksen, D., Galhardo, J., Kanaka-Gantenbein, C., Rami-Merhar, B., Madacsy, L. 2016; 17: 38-45

  Abstract

  Intensified insulin delivery using multiple daily injections (MDI) or continuous subcutaneous insulin infusion (CSII) is recommended in children with type 1 diabetes (T1D) to achieve good metabolic control.To examine the frequency of pump usage in T1D children treated in SWEET (Better control in Paediatric and Adolescent diabeteS: Working to crEate CEnTers of Reference) centers and to compare metabolic control between patients treated with CSII vs MDI.This study included 16 570 T1D children participating in the SWEET prospective, multicenter, standardized diabetes patient registry. Datasets were aggregated over the most recent year of treatment for each patient. Data were collected until March 2016. To assess the organization of pump therapy a survey was carried out.Overall, 44.4% of T1D children were treated with CSII. The proportion of patients with pump usage varied between centers and decreased with increasing age compared with children treated with MDI. In a logistic regression analysis adjusting for age, gender and diabetes duration, the use of pump was associated with both: center size [odd ratio 1.51 (1.47-1.55), P < .0001) and the diabetes-related expenditure per capita [odd ratio 1.55 (1.49-1.61), P < .0001]. Linear regression analysis, adjusted for age, gender, and diabetes duration showed that both HbA1c and daily insulin dose (U/kg/d) remained decreased in children treated with CSII compared to MDI (P < .0001).Insulin pump therapy is offered by most Sweet centers. The differences between centers affect the frequency of use of modern technology. Despite the heterogeneity of centers, T1D children achieve relatively good metabolic control, especially those treated with insulin pumps and those of younger age.

  View details for DOI 10.1111/pedi.12416

  View details for Web of Science ID 000389153800006

  View details for PubMedID 27417128

• The Gomez' equations and renal hemodynamic function in kidney disease research. American journal of physiology. Renal physiology Bjornstad, P., ?krtic, M., Lytvyn, Y., Maahs, D. M., Johnson, R. J., Cherney, D. Z. 2016: ajprenal 00415 2016-?

  Abstract

  Diabetic kidney disease (DKD) remains the leading cause of end-stage renal disease. A major challenge in preventing DKD is the difficulty in identifying high-risk patients at an early, pre-clinical stage. Albuminuria and eGFR as measures of renal function in DKD research and clinical practice are limited by regression of one-third of patients with microalbuminuria to normoalbuminuria and eGFR is biased and imprecise in the normal-elevated range. Moreover, existing methods that are used to assess renal function do not give detailed insight into the location of the renal hemodynamic effects of pharmacological agents at the segmental level. To gain additional information about the intrarenal circulation in-vivo in humans, mathematical equations were developed by Gomez et al in the 1950s. These equations used measurements of GFR, renal blood flow (RBF), effective renal plasma flow (ERPF), renal vascular resistance (RVR), hematocrit and serum protein to calculate afferent and efferent arteriolar resistances, glomerular hydrostatic pressure and filtration pressure. Although indirect and based on physiological assumptions, these techniques have the potential to improve researchers' ability to identify early pre-clinical changes in renal hemodynamic function in patients with a variety of conditions including DKD, thereby offering tremendous potential in mechanistic human research studies. In this review, we focus on the application of Gomez' equations and summarize the potential and limitations of this technique in DKD research. We also summarize illustrative data derived from Gomez' equations in patients with type 1 (T1D) and type 2 diabetes (T2D) and hypertension.

  View details for DOI 10.1152/ajprenal.00415.2016

  View details for PubMedID 27605583

• Elevated copeptin is associated with atherosclerosis and diabetic kidney disease in adults with type 1 diabetes. Journal of diabetes and its complications Bjornstad, P., Maahs, D. M., Jensen, T., Lanaspa, M. A., Johnson, R. J., Rewers, M., Snell-Bergeon, J. K. 2016; 30 (6): 1093-1096

  Abstract

  Vasopressin exerts important cardio-renal effects, but remains problematic to measure. Copeptin is a more stable peptide derived from the same precursor molecule. We examined the associations between copeptin, coronary artery calcium (CAC), albuminuria and impaired glomerular filtration rate (GFR) in adults with type 1 diabetes (T1D).Participants with (n=209) and without T1D (n=244) in the Coronary Artery Calcification in Type 1 Diabetes (CACTI) study were assessed for serum copeptin, CAC measured using 128-slice spiral CT, urinary albumin-to-creatinine ratio (UACR) and eGFR calculated by CKD-EPI creatinine. Impaired GFR was defined as eGFR <60mL/min/1.73m(2), albuminuria as UACR ?30mg/g, high and very high CAC score as ?100 and ?300AU, and elevated copeptin as >13pmol/L (>97.5th percentile for healthy adults). Unadjusted and adjusted (age, sex, HbA1c, SBP and LDL-C) logistic models were applied to examine the relationships.Participants with T1D had greater ultrasensitive copeptin concentrations than non-diabetics (3.5 [95% CI 2.3-3.8] vs. 2.8 [2.7-3.1], p=0.003). In participants with T1D, elevated copeptin was associated with greater odds of impaired eGFR (OR: 18.52, 95% CI 4.03-85.02), albuminuria (10.55, 2.24-49.62), high CAC (6.61, 1.39-31.31) and very high CAC (6.24, 1.51-25.90) in multivariable models. Similar linear relationships were obtained with ultrasensitive copeptin, eGFR, UACR, CAC volume and CAC score in adjusted models.In this cross-sectional analysis, copeptin was strongly associated with diabetic kidney disease and coronary atherosclerosis in adults with T1D. Further research is needed to determine whether these relationships hold true longitudinally in people with T1D.

  View details for DOI 10.1016/j.jdiacomp.2016.04.012

  View details for PubMedID 27141815

  View details for PubMedCentralID PMC4949105

• Continuous Glucose Sensor Survival and Accuracy Over 14 Consecutive Days DIABETES CARE DeSalvo, D. J., Ly, T. T., Wadwa, R., Messer, L., Westfall, E., Gopisetty, D., Hanes, S., von Eyben, R., Maahs, D. M., Buckingham, B. A. 2016; 39 (8): E112?E113

  View details for PubMedID 27222506

  View details for PubMedCentralID PMC4955929

• Hemoglobin A1c (HbA1c) changes over time among adolescent and young adult participants in the T1D exchange clinic registry PEDIATRIC DIABETES Clements, M. A., Foster, N. C., Maahs, D. M., Schatz, D. A., Olson, B. A., Tsalikian, E., Lee, J. M., Burt-Solorzano, C. M., Tamborlane, W. V., Chen, V., Miller, K. M., Beck, R. W. 2016; 17 (5): 327-336

  Abstract

  Hemoglobin A1c (HbA1c) levels among individuals with type 1 diabetes (T1D) influence the longitudinal risk for diabetes-related complications. Few studies have examined HbA1c trends across time in children, adolescents, and young adults with T1D. This study examines changes in glycemic control across the specific transition periods of pre-adolescence-to-adolescence and adolescence-to-young adulthood, and the demographic and clinical factors associated with these changes.Available HbA1c lab results for up to 10 yr were collected from medical records at 67 T1D Exchange clinics. Two retrospective cohorts were evaluated: the pre-adolescent-to-adolescent cohort consisting of 85 016 HbA1c measurements from 6574 participants collected when the participants were 8-18 yr old and the adolescent-to-young adult cohort, 2200 participants who were 16-26 yr old at the time of 17 279 HbA1c measurements.HbA1c in the 8-18 cohort increased over time after age 10 yr until ages 16-17; followed by a plateau. HbA1c levels in the 16-26 cohort remained steady from 16-18, and then gradually declined. For both cohorts, race/ethnicity, income, health insurance, and pump use were all significant in explaining individual variations in age-centered HbA1c (p < 0.001). For the 8-18 cohort, insulin pump use, age of onset, and health insurance were significant in predicting individual HbA1c trajectory.Glycemic control among patients 8-18 yr old worsens over time, through age 16. Elevated HbA1c levels observed in 18 yr-olds begin a steady improvement into early adulthood. Focused interventions to prevent deterioration in glucose control in pre-adolescence, adolescence, and early adulthood are needed.

  View details for DOI 10.1111/pedi.12295

  View details for Web of Science ID 000379832500003

  View details for PubMedID 26153338

• Ketone production in children with type 1 diabetes, ages 4-14 years, with and without nocturnal insulin pump suspension. Pediatric diabetes Wadwa, R. P., Chase, H. P., Raghinaru, D., Buckingham, B. A., Hramiak, I., Maahs, D. M., Messer, L., Ly, T., Aye, T., Clinton, P., Kollman, C., Beck, R. W., Lum, J. 2016

  Abstract

  To compare the frequency of elevated morning blood ketone levels according to age in 4-14 year olds with type 1 diabetes following overnight use of an automated low glucose insulin suspension system, or following control nights when the system was not used.For 28 children ages 4-9 years and 54 youth ages 10-14 years, elevation of morning blood ketone levels was assessed using the Precision Xtra Ketone meter following 1155 and 2345 nights, respectively. Repeated measures logistic regression models were used to compare age groups for blood ketone level elevation following control nights (system not activated) and following intervention nights with and without insulin suspension.Elevated morning blood ketones (?0.6 mmol/L) were present following 10% of 580 control nights in the 4-9 year olds compared with 2% of 1162 control nights in 10-14 year olds (P < 0.001). Likewise, the frequency was greater following intervention nights in the younger age group (13% of 575 nights vs 2% of 1183 nights, P < 0.001). A longer duration of pump suspension resulted in a higher percentage of mornings with elevated blood ketones in the younger age group (P = 0.002), but not in the older age group (P = 0.63). The presence of elevated morning ketone levels did not progress to ketoacidosis in any subject.Elevated morning blood ketones are more common in younger children with type 1 diabetes with or without nocturnal insulin suspension. Care providers need to be aware of the differences in ketogenesis in younger age children relative to various clinical situations.

  View details for DOI 10.1111/pedi.12410

  View details for PubMedID 27402452

• Duration of Infusion Set Survival in Lipohypertrophy Versus Nonlipohypertrophied Tissue in Patients with Type 1 Diabetes DIABETES TECHNOLOGY & THERAPEUTICS Karlin, A. W., Ly, T. T., Pyle, L., Forlenza, G. P., Messer, L., Wadwa, R. P., DeSalvo, D. J., Payne, S. L., Hanes, S., Clinton, P., Maahs, D. M., Buckingham, B. 2016; 18 (7): 429-435

  Abstract

  Improved insulin infusion set survival and faster insulin action are important issues for pump users and for the development of an artificial pancreas. The current recommendation is to change infusion sets every 3 days. Our objectives were to determine the effect of lipohypertrophy (LH) on infusion set survival and continuous glucose monitoring glucose levels.In this multicenter crossover trial, we recruited 20 subjects (age 28.1?±?9.0 years) with type 1 diabetes (duration 17.5?±?8.8 years) and an area of lipohypertrophied tissue >3?cm. Subjects alternated weekly wearing a Teflon infusion set in an area of either LH or non-LH for 4 weeks. Sets were changed after (a) failure or (b) surviving 7 days of use.The least-squares mean duration of infusion set survival for sets that lasted <7 days in lipohypertrophied tissue was 4.31 days compared with 4.12 days in nonlipohypertrophied tissue (P?=?0.71). The average duration of set survival for individual subjects ranged from 2.2 to 7.0 days. Infusion sets in lipohypertrophied tissue failed due to hyperglycemia in 35% of subjects compared with 23% in nonlipohypertrophied tissue (P?=?0.22). Both lipohypertrophied and nonlipohypertrophied tissues displayed a general increase in mean daily glucose after the third day of infusion set wear, but daily mean glucose did not differ by tissue type (P?>?0.38 on each day).LH did not significantly affect infusion set survival or mean glucose. Achieving optimal infusion set performance requires research into factors affecting set survival. Additionally, the recommendation for duration of set change may need to be individualized.

  View details for DOI 10.1089/dia.2015.0432

  View details for Web of Science ID 000379497600006

  View details for PubMedID 27227290

  View details for PubMedCentralID PMC4931738

• Outcome Measures for Artificial Pancreas Clinical Trials: A Consensus Report. Diabetes care Maahs, D. M., Buckingham, B. A., Castle, J. R., Cinar, A., Damiano, E. R., Dassau, E., DeVries, J. H., Doyle, F. J., Griffen, S. C., Haidar, A., Heinemann, L., Hovorka, R., Jones, T. W., Kollman, C., Kovatchev, B., Levy, B. L., Nimri, R., O'Neal, D. N., Philip, M., Renard, E., Russell, S. J., Weinzimer, S. A., Zisser, H., Lum, J. W. 2016; 39 (7): 1175-1179

  Abstract

  Research on and commercial development of the artificial pancreas (AP) continue to progress rapidly, and the AP promises to become a part of clinical care. In this report, members of the JDRF Artificial Pancreas Project Consortium in collaboration with the wider AP community 1) advocate for the use of continuous glucose monitoring glucose metrics as outcome measures in AP trials, in addition to HbA1c, and 2) identify a short set of basic, easily interpreted outcome measures to be reported in AP studies whenever feasible. Consensus on a broader range of measures remains challenging; therefore, reporting of additional metrics is encouraged as appropriate for individual AP studies or study groups. Greater consistency in reporting of basic outcome measures may facilitate the interpretation of study results by investigators, regulatory bodies, health care providers, payers, and patients themselves, thereby accelerating the widespread adoption of AP technology to improve the lives of people with type 1 diabetes.

  View details for DOI 10.2337/dc15-2716

  View details for PubMedID 27330126

• Reduced brachial artery distensibility in patients with type 1 diabetes JOURNAL OF DIABETES AND ITS COMPLICATIONS Ljunggren, P., Maahs, D. M., Johansson, P., Ludvigsson, J., Pyle, L., Sippl, R., Wadwa, R. P., Snell-Bergeon, J. 2016; 30 (5): 893-897

  Abstract

  In patients with type 1 diabetes mellitus (T1D), cardiovascular disease (CVD) events are more common and occur earlier in life than in non-diabetics. Reduced brachial artery distensibility (BrachD) is an independent risk factor for development of CVD. Our aim was to determine if adults with T1D have lower BrachD compared to adults without diabetes and also to determine how age and gender affect the relationship of BrachD with T1D status.BrachD was measured using the Dynapulse instrument in 829 participants (352 with T1D, 477 non-diabetics). An ANCOVA model was used to test the association of BrachD with age, sex, and T1D, and the significance of an age*sex*T1D interaction.Mean BrachD was lower in T1D patients vs. controls (6.43±1.46 vs. 7.16±1.48 % change per mmHg, p<0.0001). In a model adjusted for age, T1D, and sex, the interaction of age*T1D*sex was significant (p=0.0045). Younger women both with and without T1D had higher BrachD than men with and without T1D, but older women with and without T1D had lower BrachD compared to older men with and without T1D. Women with T1D had a steeper decline in BrachD with age than nondiabetic women.BrachD is lower in T1D patients than in non-diabetics, indicating increased vascular stiffness. Younger females have higher BrachD than males, but the decline with age in BrachD is steeper for women, particularly among those with T1D. BrachD may be an inexpensive, non-invasive method to ascertain increased CVD risk in this population.

  View details for DOI 10.1016/j.jdiacomp.2016.03.004

  View details for PubMedID 27056753

  View details for PubMedCentralID PMC4912899

• Adiponectin is associated with early diabetic kidney disease in adults with type 1 diabetes: A Coronary Artery Calcification in Type 1 Diabetes (CACTI) Study. Journal of diabetes and its complications Bjornstad, P., Pyle, L., Kinney, G. L., Rewers, M., Johnson, R. J., Maahs, D. M., Snell-Bergeon, J. K. 2016

  Abstract

  The associations between elevated adiponectin and end-stage renal disease are well recognized and thought to be at least partially explained by reduced renal clearance. Conversely, the relationship between adiponectin and early diabetic kidney disease (DKD) with preserved glomerular filtration rate (GFR), including rapid GFR decline and incident chronic kidney disease (CKD) is unclear. We hypothesized that elevated adiponectin would be associated with early DKD in adults with type 1 diabetes.Adults with type 1 diabetes (n=646 at baseline, n=525 at 6years) had adiponectin and renal function by estimated GFR (eGFR) by CKD-EPI creatinine and albumin-excretion rate (AER) evaluated at baseline and 6years. Linear and logistic models evaluated the associations of baseline adiponectin with AER, macroalbuminuria (AER ?200?g/min), eGFR, CKD (<60mL/min/1.73m(2)) and rapid GFR decline (>3mL/min/1.73m(2)/year). Models adjusted for age, sex, duration, HbA1c, SBP, LDL-C and current smoking.Compared to non-diabetics, adults with type 1 diabetes had significantly higher adiponectin, and the difference remained significant after adjusting for AER and/or eGFR (p<0.0001). Adiponectin at baseline was positively associated with rapid GFR decline (OR: 1.24, 95% CI 1.00-1.53), incident CKD (OR: 1.75, 1.14-2.70), and persistent macroalbuminuria and CKD (OR: 1.61, 1.10-2.36) over 6years in adjusted models. The associations also remained significant after further adjustments for CRP, estimated insulin sensitivity and ACEi/ARB therapy.Adults with type 1 diabetes have higher adiponectin than their non-diabetic peers, and elevated adiponectin at baseline is independently associated with greater odds of developing early DKD over 6years.

  View details for DOI 10.1016/j.jdiacomp.2016.06.012

  View details for PubMedID 27368123

  View details for PubMedCentralID PMC5156602

• The dose-response effect of insulin sensitivity on albuminuria in children according to diabetes type PEDIATRIC NEPHROLOGY Mottl, A. K., Divers, J., Dabelea, D., Maahs, D. M., Dolan, L., Pettitt, D., Marcovina, S., Imperatore, G., Pihoker, C., Mauer, M., Mayer-Davis, E. J. 2016; 31 (6): 933-940

  Abstract

  Insulin resistance is associated with microalbuminuria among youth with diabetes mellitus. We sought to determine the dose-response effect of insulin sensitivity (IS) on the magnitude of albuminuria and whether there is a threshold below which urine albumin excretion increases.These analyses included participants from the SEARCH for Diabetes in Youth Study with incident diabetes who completed a baseline study visit (n = 2988). We estimated IS using a validated equation incorporating waist circumference, HbA1C, and fasting serum triglycerides. Multivariate regression analyses were performed to assess the effect of IS on urine albumin creatinine ratio (UACR), stratified by diabetes type. The IS threshold was then determined using segmented regressions within each diabetes type and incorporated into the multivariate model.There was an association between IS and UACR in type 2 diabetes only (beta = -0.39; p < 0.001). There was strong statistical evidence for a threshold effect of IS score on UACR in the group of youth with type 2 (beta = 0.40; p < 0.001) but not type 1 diabetes (p = 0.3).In cross-sectional analyses, there is a negative association between IS and UACR in youth with type 2 but not type 1 diabetes, and this association likely includes a threshold effect of IS on UACR.

  View details for DOI 10.1007/s00467-015-3276-2

  View details for Web of Science ID 000374579700007

  View details for PubMedID 26754041

  View details for PubMedCentralID PMC4841707

• Lipoprotein subfraction cholesterol distribution is more atherogenic in insulin resistant adolescents with type 1 diabetes PEDIATRIC DIABETES Cree-Green, M., Maahs, D. M., Ferland, A., Hokanson, J. E., Wang, H., Pyle, L., Kinney, G. L., King, M., Eckel, R. H., Nadeau, K. J. 2016; 17 (4): 257-265

  Abstract

  Adolescents with type 1 diabetes (T1D) often have a less atherogenic-appearing fasting lipid profile than controls, despite increased rates of cardiovascular disease (CVD) as adults. We previously reported an atherogenic lipoprotein subfraction cholesterol distribution associated with insulin resistance (IR) in T1D adults. We sought to determine if T1D youth have more atherogenic profile than controls via a cross-sectional study.Following 3 days of controlled diet and restricted exercise, fasting plasma samples were drawn from 28 T1D youth [50% female, age 15.3 ± 2 yr, body mass index (BMI) 48%ile; diabetes duration 73 ± 52 months, hemoglobin A1c (HbA1c) 8.3 ± 1.4%] and 17 non-diabetic controls (47% female, age: 15.0 ± 2 yr, BMI 49%ile) prior to a hyperinsulinemic euglycemic clamp. Lipoproteins were fractionated by fast protein liquid chromatography (FPLC) and lipoprotein cholesterol distribution determined. Outcome measures were IR assessed by glucose infusion rate (GIR) and FPLC lipoprotein subfraction cholesterol distribution.T1D youth were more IR (GIR 9.1 ± 3.6 vs. 14.7 ± 3.9 mg/kg/min, p < 0.0001) and had more cholesterol distributed as small dense low density lipoprotein-cholesterol (LDL-C) and less as large buoyant high density lipoprotein-cholesterol (HDL-C) than controls (p < 0.05), despite no differences in the fasting lipid panel. T1D girls lacked the typical female less-atherogenic profile, whereas control girls tended to have a shift toward less dense LDL-C and HDL-C vs. control boys. Among T1D, IR but not HbA1c was associated with a more atherogenic lipoprotein profile.Normal weight T1D youth, especially females, had more atherogenic LDL-C and HDL-C distributions which correlated with lower insulin sensitivity. IR may contribute to the increased CVD burden in T1D.

  View details for DOI 10.1111/pedi.12277

  View details for Web of Science ID 000379831900004

  View details for PubMedID 26080650

  View details for PubMedCentralID PMC4887262

• Automated hybrid closed-loop control with a proportional-integral-derivative based system in adolescents and adults with type 1 diabetes: individualizing settings for optimal performance. Pediatric diabetes Ly, T. T., Weinzimer, S. A., Maahs, D. M., Sherr, J. L., Roy, A., Grosman, B., Cantwell, M., Kurtz, N., Carria, L., Messer, L., von Eyben, R., Buckingham, B. A. 2016

  Abstract

  Automated insulin delivery systems, utilizing a control algorithm to dose insulin based upon subcutaneous continuous glucose sensor values and insulin pump therapy, will soon be available for commercial use. The objective of this study was to determine the preliminary safety and efficacy of initialization parameters with the Medtronic hybrid closed-loop controller by comparing percentage of time in range, 70-180 mg/dL (3.9-10 mmol/L), mean glucose values, as well as percentage of time above and below target range between sensor-augmented pump therapy and hybrid closed-loop, in adults and adolescents with type 1 diabetes.We studied an initial cohort of 9 adults followed by a second cohort of 15 adolescents, using the Medtronic hybrid closed-loop system with the proportional-integral-derivative with insulin feed-back (PID-IFB) algorithm. Hybrid closed-loop was tested in supervised hotel-based studies over 4-5 days.The overall mean percentage of time in range (70-180 mg/dL, 3.9-10 mmol/L) during hybrid closed-loop was 71.8% in the adult cohort and 69.8% in the adolescent cohort. The overall percentage of time spent under 70 mg/dL (3.9 mmol/L) was 2.0% in the adult cohort and 2.5% in the adolescent cohort. Mean glucose values were 152 mg/dL (8.4 mmol/L) in the adult cohort and 153 mg/dL (8.5 mmol/L) in the adolescent cohort.Closed-loop control using the Medtronic hybrid closed-loop system enables adaptive, real-time basal rate modulation. Initializing hybrid closed-loop in clinical practice will involve individualizing initiation parameters to optimize overall glucose control.

  View details for DOI 10.1111/pedi.12399

  View details for PubMedID 27191182

• Estimated insulin sensitivity predicts incident micro- and macrovascular complications in adults with type 1 diabetes over 6 years: the coronary artery calcification in type 1 diabetes study JOURNAL OF DIABETES AND ITS COMPLICATIONS Bjornstad, P., Maahs, D. M., Duca, L. M., Pyle, L., Rewers, M., Johnson, R. J., Snell-Bergeon, J. K. 2016; 30 (4): 586-590

  Abstract

  Reduced insulin sensitivity (IS) is well documented in type 1 diabetes (T1D) and may contribute to vascular complications. We examined the association of estimated IS (eIS) with incident macro- and microvascular complications in adults with T1D in the prospective CACTI study.Participants (N=652) were 19-56 years old at baseline and re-examined 6.2±0.6years later. Urinary albumin excretion was measured, and categorized as microalbuminuria or greater. Diabetic retinopathy (DR) was based on self-reported history, proliferative DR (PDR) as history of laser eye therapy and coronary artery calcium (CAC) was measured using electron-beam CT. Progression of CAC was defined as a change in the square root transformed CAC volume score of ?2.5. IS was estimated (eIS) by an equation derived from clamp studies. Predictors of each complication were examined using stepwise logistic regression and subjects with complications at baseline excluded. Age, T1D duration, sex, HbA1c, SBP, LDL-C, and eIS were considered for inclusion.Greater eIS at baseline predicted lower odds of developing albuminuria (OR: 0.67, 95% CI 0.51-0.88), DR (OR 0.79, 0.64-0.97), PDR (OR: 0.76, 0.57-0.99) and CACp (OR: 0.71, 0.60-0.85) in multivariable models.Greater eIS conferred protection from the development of vascular complications over 6-years in T1D.

  View details for DOI 10.1016/j.jdiacomp.2016.02.011

  View details for Web of Science ID 000374916200004

  View details for PubMedID 26936306

  View details for PubMedCentralID PMC4834265

• Hyperfiltration and uricosuria in adolescents with type 1 diabetes PEDIATRIC NEPHROLOGY Bjornstad, P., Roncal, C., Milagres, T., Pyle, L., Lanaspa, M. A., Bishop, F. K., Snell-Bergeon, J. K., Johnson, R. J., Wadwa, R. P., Maahs, D. M. 2016; 31 (5): 787-793

  Abstract

  Urine uric acid (UUA) has been implicated in the pathogenesis of diabetic nephropathy via its effect on tubular cells. We hypothesized that the UUA level would be higher in adolescents with type 1 diabetes (T1D) than in those without T1D. We also hypothesized that UUA and fractional uric acid excretion (FeUA) would be higher in adolescents with T1D and hyperfiltration [estimated glomerular filtration rate (eGFR) ?141 mL/min/1.73 m(2)] than in those without hyperfiltration.The UUA concentration was determined and FeUA calculated in adolescents with (n?=?239) and without T1D (n?=?75). The eGFR was calculated using the Zappitelli equation based on serum creatinine and cystatin C concentrations.Compared to the non-diabetic adolescents enrolled in the study, those with T1D had a higher eGFR (mean?±?standard deviation: 120?±?22 vs. 112?±?16 mL/min/1.73 m(2); p?=?0.0006), lower urine pH (6.2?±?0.8 vs. 6.5?±?1.0; p =?0.01), and higher UUA (37.7?±?18.6 vs. 32.8?±?18.1 mg/dL; p ?=?0.049) and FeUA (median [interquartile range]: 6.2 [4.3-8.7] vs. 5.2 [3.6-7.0] %; p?=?0.02). Among adolescents with T1D, those with hyperfiltration had higher median FeUA (8.6 [5.2-9.9] vs. 6.0 [4.2-8.3] %; p?=?0.02) than those without hyperfiltration.The adolescents with T1D enrolled in the study had higher eGFR, higher UUA and more acidic urine than the non-diabetic controls, which may have increased their risk of UUA crystallization. Adolescents with T1D and hyperfiltration had higher FeUA than those without hyperfiltration. These hypothesis-generating observations may suggest a potential pathophysiologic association between uricosuria and hyperfiltration.

  View details for DOI 10.1007/s00467-015-3299-8

  View details for Web of Science ID 000373305100012

  View details for PubMedID 26701836

  View details for PubMedCentralID PMC4808359

• In-home nighttime predictive low glucose suspend experience in children and adults with type 1 diabetes. Pediatric diabetes Messer, L. H., Calhoun, P., Buckingham, B., Wilson, D. M., Hramiak, I., Ly, T. T., Driscoll, M., Clinton, P., Maahs, D. M. 2016: -?

  Abstract

  Overnight predictive low glucose suspend (PLGS) reduces hypoglycemia across all ages; however, there are no reports on behavior or experience differences across age groups, especially in pediatrics. As run-in for a subsequent randomized clinical trial (RCT), 127 subjects (50% male) ages 4-45?yr utilized the experimental PLGS system nightly for 5-10 nights (PLGS active phase). We analyzed the number of blood glucose (BG) checks and boluses given per age group. During the subsequent 42 night RCT phase, we analyzed sensor use, skin reactions, errors, and reasons why the experimental system was not used. In 821 nights of active PLGS, subjects ages 4-6?yr (and their parents) tested BG levels 75% of nights compared with 65% of nights (7-10?yr), 53% of nights (11-14?yr), 33% of nights (15-25?yr), and 28% of nights (26-45?yr), respectively (p?270 at bedtime (study requirement) were primary contributors to non-system use. Understanding the different use patterns and challenges in pediatrics and adolescence is needed to direct patient education to optimize use of PLGS and future artificial pancreas systems.

  View details for DOI 10.1111/pedi.12395

  View details for PubMedID 27125223

  View details for PubMedCentralID PMC5086306

• Measuring glomerular filtration rate by iohexol clearance on filter paper is feasible in adolescents with type 1 diabetes in the ambulatory setting ACTA DIABETOLOGICA Bjornstad, P., Anderson, P. L., Maahs, D. M. 2016; 53 (2): 331-333

  View details for DOI 10.1007/s00592-015-0764-6

  View details for Web of Science ID 000373951300018

  View details for PubMedID 25959420

  View details for PubMedCentralID PMC4643415

• Prevalence of cardiovascular risk factors in youth with type 1 diabetes and elevated body mass index. Acta diabetologica Redondo, M. J., Foster, N. C., Libman, I. M., Mehta, S. N., Hathway, J. M., Bethin, K. E., Nathan, B. M., Ecker, M. A., Shah, A. C., DuBose, S. N., Tamborlane, W. V., Hoffman, R. P., Wong, J. C., Maahs, D. M., Beck, R. W., Dimeglio, L. A. 2016; 53 (2): 271-277

  Abstract

  The prevalence of cardiovascular risk factors in children with type 1 diabetes and elevated BMI in the USA is poorly defined. We aimed to test the hypothesis that children with type 1 diabetes who are overweight or obese have increased frequencies of hypertension, dyslipidemia, and micro-/macroalbuminuria compared to their healthy weight peers.We studied 11,348 children 2 to <18 years of age enrolled in T1D Exchange between September 2010 and August 2012 with type 1 diabetes for ?1 year and BMI ? 5th age-/sex-adjusted percentile (mean age 12 years, 49 % female, 78 % non-Hispanic White). Overweight and obesity were defined based on Centers for Disease Control and Prevention criteria. Diagnoses of hypertension, dyslipidemia, and micro-/macroalbuminuria were obtained from medical records. Logistic and linear regression models were used to assess factors associated with weight status.Of the 11,348 participants, 22 % were overweight and 14 % obese. Hypertension and dyslipidemia were diagnosed in 1.0 % and 3.8 % of participants, respectively; micro-/macroalbuminuria was diagnosed in 3.8 % of participants with available data (n = 7,401). The odds of either hypertension or dyslipidemia were higher in obese than healthy weight participants [OR 3.5, 99 % confidence interval (CI) 2.0-6.1 and 2.2, 99 % CI 1.6-3.1, respectively]. Obese participants tended to be diagnosed with micro-/macroalbuminuria less often than healthy weight participants (OR 0.6, 99 % CI 0.4-1.0).Obese children with type 1 diabetes have a higher prevalence of hypertension and dyslipidemia than healthy weight children with type 1 diabetes. The possible association of obesity with lower micro-/macroalbuminuria rates warrants further investigation.

  View details for DOI 10.1007/s00592-015-0785-1

  View details for PubMedID 26077171

• Periodontal Microorganisms and Cardiovascular Risk Markers in Youth With Type 1 Diabetes and Without Diabetes JOURNAL OF PERIODONTOLOGY Merchant, A. T., Nahhas, G. J., Wadwa, R. P., Zhang, J., Tang, Y., Johnson, L. R., Maahs, D. M., Bishop, F., Teles, R., Morrato, E. H. 2016; 87 (4): 376-384

  Abstract

  A subset of periodontal microorganisms has been associated with cardiovascular disease (CVD), which is the leading complication of type 1 diabetes (t1DM). The authors therefore evaluated the association between periodontal microorganism groups and early markers of CVD in youth with t1DM.A cross-sectional analysis was conducted among youth aged 12 to 19 years at enrollment; 105 had t1DM for ?5 years and were seeking care at the Barbara Davis Center, University of Colorado, from 2009 to 2011, and 71 did not have diabetes. Subgingival plaque samples were assessed for counts of 41 periodontal microorganisms using DNA-DNA hybridization. Microorganisms were classified using cluster analysis into four groups named red-orange, orange-green, blue/other, and yellow/other, modified from Socransky's color scheme for periodontal microorganisms. Subsamples (54 with t1DM and 48 without diabetes) also received a periodontal examination at the University of Colorado School of Dental Medicine.Participants were ?15 years old on average, and 74% were white. Mean periodontal probing depth was 2 mm (SE 0.02), and 17% had bleeding on probing. In multivariable analyses, glycated hemoglobin (HbA1c) was inversely associated with the yellow/other cluster (microorganisms that are not associated with periodontal disease) among youth with t1DM. Blood pressure, triglycerides, low-density lipoprotein, high-density lipoprotein, and total cholesterol were not associated with microorganism clusters in this group. HbA1c was not associated with periodontal microorganism clusters among youth without diabetes.Among youth with t1DM who had good oral health, periodontal microorganisms were not associated with CVD risk factors.

  View details for DOI 10.1902/jop.2015.150531

  View details for Web of Science ID 000375842800008

  View details for PubMedID 26616842

• Profound hypokalemia associated with severe diabetic ketoacidosis PEDIATRIC DIABETES Davis, S. M., Maddux, A. B., Alonso, G. T., Okada, C. R., Mourani, P. M., Maahs, D. M. 2016; 17 (1): 61-65

  Abstract

  Hypokalemia is common during the treatment of diabetic ketoacidosis (DKA); however, severe hypokalemia at presentation prior to insulin treatment is exceedingly uncommon. A previously healthy 8-yr-old female presented with new onset type 1 diabetes mellitus, severe DKA (pH = 6.98), and profound hypokalemia (serum K = 1.3 mmol/L) accompanied by cardiac dysrhythmia. Insulin therapy was delayed for 9 h to allow replenishment of potassium to safe serum levels. Meticulous intensive care management resulted in complete recovery. This case highlights the importance of measuring serum potassium levels prior to initiating insulin therapy in DKA, judicious fluid and electrolyte management, as well as delaying and/or reducing insulin infusion rates in the setting of severe hypokalemia.

  View details for DOI 10.1111/pedi.12246

  View details for Web of Science ID 000367723000008

  View details for PubMedID 25430801

  View details for PubMedCentralID PMC4896141

• Progress in Diabetes Technology: Developments in Insulin Pumps, Continuous Glucose Monitors, and Progress towards the Artificial Pancreas JOURNAL OF PEDIATRICS Forlenza, G. P., Buckingham, B., Maahs, D. M. 2016; 169: 13-20

  View details for DOI 10.1016/j.jpeds.2015.10.015

  View details for Web of Science ID 000368595300006

  View details for PubMedID 26547403

• Development and Validation of a Method to Estimate Insulin Sensitivity in Patients With and Without Type 1 Diabetes JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM Duca, L. M., Maahs, D. M., Schauer, I. E., Bergman, B. C., Nadeau, K. J., Bjornstad, P., Rewers, M., Snell-Bergeon, J. K. 2016; 101 (2): 686-695

  Abstract

  People with type 1 diabetes (T1D) have markedly reduced insulin sensitivity (IS) compared to their nondiabetic counterparts, and reduced IS is linked to higher cardiovascular risk.This study aimed to develop and validate an improved method for estimating IS in people with T1D.Prospective cohort.Adults (36 with T1D, 41 nondiabetic) were recruited from the Coronary Artery Calcification in Type 1 Diabetes (CACTI) study for measurement of IS by hyperinsulinemic-euglycemic clamp to develop a clinically useful IS prediction equation (eIS) for T1D and nondiabetic individuals. These equations were then compared with previously published equations from the SEARCH and Pittsburgh Epidemiology of Diabetes Complications studies for the ability to predict measured IS in test sets of adults and adolescents from independent clamp studies.None.Comparison of clamp-measured IS to estimated IS.The best-fit prediction model (eIS) differed by diabetes status and included waist circumference, triglycerides, adiponectin, and diastolic blood pressure in all CACTI adults and insulin dose in adults with T1D (adjusted R(2) = 0.64) or fasting glucose and hemoglobin A1c (HbA1c) in nondiabetic adults (adjusted R(2) = 0.63). The eIS highly correlated with clamp-measured IS in all of the non-CACTI comparison populations (r = 0.83, P = .0002 in T1D adults; r = 0.71, P = .01 in nondiabetic adults; r = 0.44, P = .008 in T1D adolescents; r = 0.44, P = .006 in nondiabetic adolescents).eIS performed better than previous equations for estimating IS in individuals with and without T1D. These equations could simplify point-of-care assessment of IS to identify patients who could benefit from targeted intervention.

  View details for DOI 10.1210/jc.2015-3272

  View details for Web of Science ID 000378642700039

  View details for PubMedID 26672636

  View details for PubMedCentralID PMC4880115

• Diabetes Technology and Therapy in the Pediatric Age Group DIABETES TECHNOLOGY & THERAPEUTICS Maahs, D. M., Shalitin, S. 2016; 18: S86-S100

  View details for DOI 10.1089/dia.2016.2509

  View details for Web of Science ID 000369672600011

  View details for PubMedID 26836433

• Therapeutic inertia: underdiagnosed and undertreated hypertension in children participating in the T1D Exchange Clinic Registry PEDIATRIC DIABETES Nambam, B., DuBose, S. N., Nathan, B. M., Beck, R. W., Maahs, D. M., Wadwa, R. P., Tamborlane, W. V., Foster, N. C., Miller, K. M., Haller, M. J. 2016; 17 (1): 15-20

  Abstract

  Reduction of cardiovascular risk in children with type 1 diabetes requires aggressive management of hypertension (HTN). However, the frequency of diagnosing and effectively treating HTN in youth with type 1 diabetes has not been established. To address this question, we used the data collected in >9000 youth with type 1 diabetes who enrolled in the T1D Exchange Clinic Registry.This analysis included data from medical records of 9362 individuals with enrolment and 1-yr follow-up visits (age 3 to <18 yr, disease duration ? 1 yr at follow-up). Data included the prevalence of a documented diagnosis of HTN, elevated blood pressure (BP) (systolic or diastolic ?95th percentile for age, gender, and height), and treatment with angiotensin converting enzyme (ACE)-receptor inhibitor (ACE-I)/angiotensin receptor blocker (ARB) therapy.HTN was diagnosed in only 1% (113/9362) of participants; yet, elevated BP was recorded at one of the two visits in 17% and at both visits in 4%. Among those with diagnosed HTN, only 52% (59/113) were receiving ACE-I/ARB therapy and only 32% (19 of 59) of those treated were at goal BP. Children with diagnosed HTN had higher HbA1c (adjusted p < 0.001) and higher BMI (p < 0.001) when compared with children without HTN.HTN is likely under diagnosed and undertreated even in pediatric diabetes clinics. The relatively low proportion of hypertensive children receiving ACE-I therapy and reaching BP goals probably identifies an important area for improving care in children with type 1 diabetes.

  View details for DOI 10.1111/pedi.12231

  View details for Web of Science ID 000367723000002

  View details for PubMedID 25330905

• Diabetic Kidney Disease in Adolescents With Type 2 Diabetes: New Insights and Potential Therapies CURRENT DIABETES REPORTS Bjornstad, P., Cherney, D. Z., Maahs, D. M., Nadeau, K. J. 2016; 16 (2)

  Abstract

  Diabetic kidney disease (DKD) is the leading cause of end-stage renal disease (ESRD) and dialysis in the Western world. Early DKD, including microalbuminuria and renal hyperfiltration, is common in adolescents with type 2 diabetes (T2D). Furthermore, youth-onset T2D carries a higher risk of progressive DKD than adult-onset T2D of similar diabetes duration. DKD is characterized by a long clinically silent period without signs of disease. Therefore, a major challenge in preventing DKD is the difficulty in identifying high-risk T2D patients at an early stage. The Type 2 Diabetes in Adolescents and Youth (TODAY) study demonstrated a high initial prevalence that increased over time, irrespective of treatment arm. This key observation underscores the importance of discovering new therapeutic targets to supplement conventional management, in order to reduce DKD risk. In this review, we focus on early DKD in T2D and summarize potential novel biomarkers and therapeutic targets.

  View details for DOI 10.1007/s11892-015-0708-0

  View details for Web of Science ID 000370358200001

  View details for PubMedID 26803647

• Use of insulin pump therapy in children and adolescents with type 1 diabetes and its impact on metabolic control: comparison of results from three large, transatlantic paediatric registries DIABETOLOGIA Sherr, J. L., Hermann, J. M., Campbell, F., Foster, N. C., Hofer, S. E., Allgrove, J., Maahs, D. M., Kapellen, T. M., Holman, N., Tamborlane, W. V., Holl, R. W., Beck, R. W., Warner, J. T. 2016; 59 (1): 87-91

  Abstract

  While the use of insulin pumps in paediatrics has expanded dramatically, there is still considerable variability among countries in the use of pump technology. The present study sought to describe differences in metabolic control and pump use in young people with type 1 diabetes using data collected in three multicentre registries.Data for the years 2011 and 2012 from 54,410 children and adolescents were collected from the Prospective Diabetes Follow-up Registry (DPV; n?=?26,198), T1D Exchange (T1DX; n?=?13,755) and the National Paediatric Diabetes Audit (NPDA; n?=?14,457). The modality of insulin delivery, based on age, sex and ethnic minority status, and the impact of pump use on HbA1c levels were compared.The overall mean HbA1c level was higher in the NPDA (8.9?±?1.6% [74?±?17.5 mmol/mol]) than in the DPV (8.0?±?1.6% [64?±?17.0 mmol/mol], p?

  View details for DOI 10.1007/s00125-015-3790-6

  View details for Web of Science ID 000365804500011

  View details for PubMedID 26546085

• Effects of Frequency of Sensor-Augmented Pump Use on HbA1c and C-Peptide Levels in the First Year of Type 1 Diabetes. Diabetes care Triolo, T. M., Maahs, D. M., Pyle, L., Slover, R., Buckingham, B., Cheng, P., DiMeglio, L. A., Bremer, A. A., Weinzimer, S. A., Chase, H. P., Diabetes Research in Children Network (DirecNet) and Type 1 Diabetes TrialNet Study Groups 2016; 39 (4): e61?2

  View details for PubMedID 26895885

• Insulin delivery methods: Past, present and future. International journal of pharmaceutical investigation Shah, R. B., Patel, M., Maahs, D. M., Shah, V. N. 2016; 6 (1): 1-9

  Abstract

  Many patients with advanced type 2 diabetes mellitus (T2DM) and all patients with T1DM require insulin to keep blood glucose levels in the target range. The most common route of insulin administration is subcutaneous insulin injections. There are many ways to deliver insulin subcutaneously such as vials and syringes, insulin pens, and insulin pumps. Though subcutaneous insulin delivery is the standard route of insulin administration, it is associated with injection pain, needle phobia, lipodystrophy, noncompliance and peripheral hyperinsulinemia. Therefore, the need exists for delivering insulin in a minimally invasive or noninvasive and in most physiological way. Inhaled insulin was the first approved noninvasive and alternative way to deliver insulin, but it has been withdrawn from the market. Technologies are being explored to make the noninvasive delivery of insulin possible. Some of the routes of insulin administration that are under investigation are oral, buccal, nasal, peritoneal and transdermal. This review article focuses on the past, present and future of various insulin delivery techniques. This article has focused on different possible routes of insulin administration with its advantages and limitation and possible scope for the new drug development.

  View details for DOI 10.4103/2230-973X.176456

  View details for PubMedID 27014614

  View details for PubMedCentralID PMC4787057

• Comparing Two Waist-to-Height Ratio Measurements with Cardiometabolic Risk Factors among Youth with Diabetes. International journal of child health and nutrition Liu, L. L., Kahn, H. S., Pettitt, D. J., Fino, N. F., Morgan, T., Maahs, D. M., Crimmins, N. A., Lamichhane, A. P., Liese, A. D., D'Agostino, R. B., Bell, R. A. 2016; 5 (3): 87-94

  Abstract

  Waist circumference (WC) is commonly measured by either the World Health Organization (WHO) or National Health and Nutrition Examination Survey (NHANES) protocol.Compare the associations of WHO vs. NHANES WC-to-height ratio (WHtR) protocols with cardiometabolic risk factors (CMRFs) in a sample of youth with diabetes.For youth (10-19 years old with type 1 [N=3082] or type 2 [N=533] diabetes) in the SEARCH for Diabetes in Youth Study, measurements were obtained of WC (by two protocols), weight, height, fasting lipids (total cholesterol, triglycerides, HDL cholesterol, Non-HDL cholesterol) and blood pressures. Associations of CMRFs with WHO and NHANES WHtR were modeled stratified by body mass index (BMI) percentiles for age/sex: lower BMI (<85(th) BMI percentile; N=2071) vs. higher BMI (?85(th) percentile; N=1594).Among lower-BMI participants, both NHANES and WHO WHtR were associated (p<0.005) with all CMRFs except blood pressure. Among higher-BMI participants, both NHANES and WHO WHtR were associated (p<0.05) with all CMRFs. WHO WHtR was more strongly associated (p<0.05) than NHANES WHtR with triglycerides, non-HDL cholesterol, and systolic blood pressure in lower-BMI participants. Among high-BMI participants, WHO WHtR was more strongly associated (p<0.05) than NHANES WHtR with triglycerides and systolic blood pressure.Among youth with diabetes, WHtR calculated from either WC protocol captures cardiometabolic risk. The WHO WC protocol may be preferable to NHANES WC.

  View details for PubMedID 28232855

• Influences of gender on cardiovascular disease risk factors in adolescents with and without type 1 diabetes. International journal of pediatric endocrinology Brown, T. L., Maahs, D. M., Bishop, F. K., Snell-Bergeon, J. K., Wadwa, R. P. 2016; 2016: 8-?

  Abstract

  Women with type 1 diabetes (T1D) have a four-fold increased risk for cardiovascular disease (CVD) compared to non-diabetic (non-DM) women, as opposed to double the risk in T1D men compared to non-DM men. It is unclear how early in life CVD risk differences begin in T1D females. Therefore, our objective was to compare CVD risk factors in adolescents with and without T1D to determine the effects of gender on CVD risk factors.The study included 300 subjects with T1D (age 15.4±2.1 years, 50 % male, 80 % non-Hispanic White (NHW), glycated hemoglobin (A1c) 8.9±1.6 %, diabetes duration 8.8±3.0 years, BMI Z-score 0.62±0.77) and 100non-DM controls (age 15.4±2.1 years, 47 % male, 69 % NHW, BMI Z-score 0.29±1.04). CVD risk factors were compared by diabetes status and gender. Multivariate linear regression analyses were used to determine if relationships between diabetes status and CVD risk factors differed by gender independent of differences in A1c and BMI.Differences in CVD risk factors between T1D subjects and non-DM controls were more pronounced in girls. Compared to boys with T1D and non-DM girls, T1D girls had higher A1c (9.0 % vs. 8.6 % and 5.1 %, respectively), BMI Z-score (0.70 vs. 0.47 and 0.27), LDL-c (95 vs. 82 and 81 mg/dL), total cholesterol (171 vs. 153 and 150 mg/dL), DBP (68 vs. 67 and 63 mmHg), and hs-CRP (1.15 vs. 0.57 and 0.54 mg/dL) after adjusting for Tanner stage, smoking status, and race/ethnicity (p <0.05 for all). In T1D girls, differences in lipids, DBP, and hs-CRP persisted even after adjusting for centered A1c and BMI Z-score. Testing interactions between gender and T1D with CVD risk factors indicated that differences were greater between girls with T1D and non-DM compared to differences between boys with T1D and non-DM. Overall, observed increases in CVD risk factors in T1D girls remained after further adjustment for centered A1c or BMI Z-score.Interventions targeting CVD risk factors in addition to lowering HbA1c and maintaining healthy BMI are needed for youth with T1D. The increased CVD risk factors seen in adolescent girls with T1D in particular argues for earlier intervention to prevent later increased risk of CVD in women with T1D.

  View details for DOI 10.1186/s13633-016-0026-6

  View details for PubMedID 27099615

  View details for PubMedCentralID PMC4837565

• Rates of Diabetic Ketoacidosis: International Comparison With 49,859 Pediatric Patients With Type 1 Diabetes From England, Wales, the US, Austria, and Germany DIABETES CARE Maahs, D. M., Hermann, J. M., Holman, N., Foster, N. C., Kapellen, T. M., Allgrove, J., Schatz, D. A., Hofer, S. E., Campbell, F., Steigleder-Schweiger, C., Beck, R. W., Warner, J. T., Holl, R. W. 2015; 38 (10): 1876-1882

  Abstract

  Diabetic ketoacidosis (DKA) in children and adolescents with established type 1 diabetes is a major problem with considerable morbidity, mortality, and associated costs to patients, families, and health care systems. We analyzed data from three multinational type 1 diabetes registries/audits with similarly advanced, yet differing, health care systems with an aim to identify factors associated with DKA admissions.Data from 49,859 individuals <18 years with type 1 diabetes duration ?1 year from the Prospective Diabetes Follow-up Registry (DPV) initiative (n = 22,397, Austria and Germany), the National Paediatric Diabetes Audit (NPDA; n = 16,314, England and Wales), and the T1D Exchange (T1DX; n = 11,148, U.S.) were included. DKA was defined as ?1 hospitalization for hyperglycemia with a pH <7.3 during the prior year. Data were analyzed using multivariable logistic regression models.The frequency of DKA was 5.0% in DPV, 6.4% in NPDA, and 7.1% in T1DX, with differences persisting after demographic adjustment (P < 0.0001). In multivariable analyses, higher odds of DKA were found in females (odds ratio [OR] 1.23, 99% CI 1.10-1.37), ethnic minorities (OR 1.27, 99% CI 1.11-1.44), and HbA1c ?7.5% (?58 mmol/mol) (OR 2.54, 99% CI 2.09-3.09 for HbA1c from 7.5 to <9% [58 to <75 mmol/mol] and OR 8.74, 99% CI 7.18-10.63 for HbA1c ?9.0% [?75 mmol/mol]).These multinational data demonstrate high rates of DKA in childhood type 1 diabetes across three registries/audits and five nations. Females, ethnic minorities, and HbA1c above target were all associated with an increased risk of DKA. Targeted DKA prevention programs could result in substantial health care cost reduction and reduced patient morbidity and mortality.

  View details for DOI 10.2337/dc15-0780

  View details for Web of Science ID 000361840500023

  View details for PubMedID 26283737

• Effect of Acetaminophen on CGM Glucose in an Outpatient Setting DIABETES CARE Maahs, D. M., DeSalvo, D., Pyle, L., Trang Ly, Messer, L., Clinton, P., Westfall, E., Wadwa, R., Buckingham, B. 2015; 38 (10): E158?E159

  View details for PubMedID 26269199

  View details for PubMedCentralID PMC4876736

• Effect of Lipohypertrophy on Accuracy of Continuous Glucose Monitoring in Patients With Type 1 Diabetes DIABETES CARE DeSalvo, D. J., Maahs, D. M., Messer, L., Wadwa, R., Payne, S., Ly, T. T., Buckingham, B. A. 2015; 38 (10): E166?E167

  View details for PubMedID 26307604

  View details for PubMedCentralID PMC4876738

• Relation of Combined Non-High-Density Lipoprotein Cholesterol and Apolipoprotein B With Atherosclerosis in Adults With Type 1 Diabetes Mellitus AMERICAN JOURNAL OF CARDIOLOGY Bjornstad, P., Eckel, R. H., Pyle, L., Rewers, M., Maahs, D. M., Snell-Bergeon, J. K. 2015; 116 (7): 1057-1062

  Abstract

  Apolipoprotein B (apoB) and non-high-density lipoprotein cholesterol (non-HDL-C) are cardiovascular disease risk markers, although data in adults with type 1 diabetes mellitus (DM) are limited. We hypothesized that elevated apoB and non-HDL-C would be associated with greater odds of coronary artery calcification progression (CACp), a measure of coronary atherosclerosis, than either category alone in adults with type 1 DM. We grouped subjects with type 1 DM (n = 652) into 4 groups: elevated apoB (?90 mg/dl) and elevated non-HDL-C (?130 mg/dl), elevated non-HDL-C alone, elevated apoB alone, and normal apoB and non-HDL-C. We used logistic regression to examine the associations between the groups and CACp for a period of 6 years. We performed sensitivity analyses with elevated apoB and non-HDL-C redefined as at or more than the cohort means (91.4 and 119.0 mg/dl, respectively). Subjects with elevated apoB and non-HDL-C had greater odds of CACp compared with those with normal apoB and non-HDL-C (odds ratio 1.90, 95% confidence interval 1.15 to 3.15) and compared with subjects with elevated apoB alone (odds ratio 2.86, 95% confidence interval 1.43 to 5.74) adjusting for age, gender, duration, hemoglobin A1c, and statins. Similar results were obtained with elevated apoB and non-HDL-C defined as at or more than the cohort means. In conclusion, elevated apoB and non-HDL-C carry a greater risk of atherosclerosis than elevated apoB in the absence of elevated non-HDL-C in adults with type 1 DM. These data suggest that apoB and non-HDL-C should be viewed as complementary rather than competitive indexes of cardiovascular disease risk in type 1 DM.

  View details for DOI 10.1016/j.amjcard.2015.07.020

  View details for Web of Science ID 000362382400011

  View details for PubMedID 26251001

  View details for PubMedCentralID PMC4567927

• Rapid GFR decline is associated with renal hyperfiltration and impaired GFR in adults with Type 1 diabetes NEPHROLOGY DIALYSIS TRANSPLANTATION Bjornstad, P., Cherney, D. Z., Snell-Bergeon, J. K., Pyle, L., Rewers, M., Johnson, R. J., Maahs, D. M. 2015; 30 (10): 1706-1711

  Abstract

  Rapid glomerular filtration rate (GFR) decline (>3 mL/min/1.73 m(2)) is an increasingly recognized high-risk diabetic nephropathy (DN) phenotype in Type 1 diabetes. Rapid GFR decline is a recognized predictor of impaired GFR (<60 mL/min/1.73 m(2)). However, the association between rapid GFR decline and renal hyperfiltration is not well described in Type 1 diabetes. We hypothesized that renal hyperfiltration (estimated glomerular filtration rate, eGFR ? 120 mL/min/1.73 m(2)) would predict rapid GFR decline over 6 years and that rapid GFR decline would predict impaired GFR at 6 years in adults with Type 1 diabetes.GFR was calculated by chronic kidney disease epidemiology (CKD-EPI) creatinine in 646 adults with Type 1 diabetes in the coronary artery calcification in Type 1 diabetes study. Logistic multivariable models were employed to investigate the relationships between renal hyperfiltration and rapid GFR decline, and rapid GFR decline and incident impaired GFR over 6 years.Renal hyperfiltration predicted greater odds of rapid GFR decline over 6 years [odds ratio (OR): 5.00, 95% confidence interval (CI): 3.03-8.25, P < 0.0001] adjusting for hemoglobin A1c (HbA1c), systolic blood pressure (SBP), low-density lipoprotein cholesterol (LDL-C), sex, duration, log of albumin/creatinine ratio and estimated insulin sensitivity. Furthermore, rapid GFR decline predicted greater odds of incident impaired eGFR (OR: 15.99, 95% CI 2.34-114.37, P = 0.006) in a similarly adjusted model. Sensitivity analyses with GFR calculated by CKD-EPI combined creatinine and cystatin C, and renal hyperfiltration defined as ?135 mL/min/1.73 m(2) yielded similar results.In adults with Type 1 diabetes, rapid GFR decline over 6 years was associated with baseline renal hyperfiltration and incident GFR impairment. These observations may suggest an intermediate and predictive role of rapid GFR decline in the progression of DN.

  View details for DOI 10.1093/ndt/gfv121

  View details for Web of Science ID 000363171900015

  View details for PubMedID 26050268

  View details for PubMedCentralID PMC4838003

• Update on Estimation of Kidney Function in Diabetic Kidney Disease CURRENT DIABETES REPORTS Bjornstad, P., Cherney, D. Z., Maahs, D. M. 2015; 15 (9)

  Abstract

  The American Diabetes Association recommends annual assessment of glomerular filtration rate (GFR) to screen for diabetic nephropathy. GFR is measured indirectly using markers that, ideally, are eliminated only by glomerular filtration. Measured GFR, although the gold standard, remains cumbersome and expensive. GFR is therefore routinely estimated using creatinine and/or cystatin C and clinical variables. In pediatrics, the Schwartz creatinine-based equation is most frequently used even though combined creatinine and cystatin C-based equations demonstrate stronger agreement with measured GFR. In adults, the CKD Epidemiology Collaboration (CKD-EPI) equations with creatinine and/or cystatin C are the most accurate and precise estimating equations. Despite recent advances, current estimates of GFR lack precision and accuracy before chronic kidney disease stage 3 (GFR?

  View details for DOI 10.1007/s11892-015-0633-2

  View details for Web of Science ID 000377953300001

  View details for PubMedID 26188736

• Erratum. Predictive Low-Glucose Insulin Suspension Reduces Duration of Nocturnal Hypoglycemia in Children Without Increasing Ketosis. Diabetes Care 2015;38:1197-1204. Diabetes care Buckingham, B. A., Raghinaru, D., Cameron, F., Bequette, B. W., Chase, H. P., Maahs, D. M., Slover, R., Wadwa, R. P., Wilson, D. M., Ly, T., Aye, T., Hramiak, I., Clarson, C., Stein, R., Gallego, P. H., Lum, J., Sibayan, J., Kollman, C., Beck, R. W. 2015; 38 (9): 1813-?

  View details for DOI 10.2337/dc15-er09

  View details for PubMedID 26294776

• Predictive Low-Glucose Insulin Suspension Reduces Duration of Nocturnal Hypoglycemia in Children Without Increasing Ketosis (vol 38, pg 1197, 2015) DIABETES CARE Buckingham, B. A., Raghinaru, D., Cameron, F., Bequette, B. W., Chase, H. P., Maahs, D. M., Slover, R., Wadwa, R. P., Wilson, D. M., Ly, T., Aye, T., Hramiak, I., Clarson, C., Stein, R., Gallego, P. H., Lum, J., Sibayan, J., Kollman, C., Beck, R. W. 2015; 38 (9): 1813-1813

  View details for DOI 10.2337/dc15-er09

  View details for Web of Science ID 000363416500037

• Obesity in Youth with Type 1 Diabetes in Germany, Austria, and the United States JOURNAL OF PEDIATRICS Dubose, S. N., Hermann, J. M., Tamborlane, W. V., Beck, R. W., Dost, A., Dimeglio, L. A., Schwab, K. O., Holl, R. W., Hofer, S. E., Maahs, D. M. 2015; 167 (3): 627-?

  Abstract

  To examine the current extent of the obesity problem in 2 large pediatric clinical registries in the US and Europe and to examine the hypotheses that increased body mass index (BMI) z-scores (BMIz) are associated with greater hemoglobin A1c (HbA1c) and increased frequency of severe hypoglycemia in youth with type 1 diabetes (T1D).International (World Health Organization) and national (Centers for Disease Control and Prevention/German Health Interview and Examination Survey for Children and Adolescents) BMI references were used to calculate BMIz in participants (age 2-<18 years and ? 1 year duration of T1D) enrolled in the T1D Exchange (n = 11,435) and the Diabetes Prospective Follow-up (n = 21,501). Associations between BMIz and HbA1c and severe hypoglycemia were assessed.Participants in both registries had median BMI values that were greater than international and their respective national reference values. BMIz was significantly greater in the T1D Exchange vs the Diabetes Prospective Follow-up (P < .001). After stratification by age-group, no differences in BMI between registries existed for children 2-5 years, but differences were confirmed for 6- to 9-, 10- to 13-, and 14- to 17-year age groups (all P < .001). Greater BMIz were significantly related to greater HbA1c levels and more frequent occurrence of severe hypoglycemia across the registries, although these associations may not be clinically relevant.Excessive weight is a common problem in children with T1D in Germany and Austria and, especially, in the US. Our data suggest that obesity contributes to the challenges in achieving optimal glycemic control in children and adolescents with T1D.

  View details for DOI 10.1016/j.jpeds.2015.05.046

  View details for Web of Science ID 000363540200027

  View details for PubMedID 26164381

• Fructose and uric acid in diabetic nephropathy DIABETOLOGIA Bjornstad, P., Lanaspa, M. A., Ishimoto, T., Kosugi, T., Kume, S., Jalal, D., Maahs, D. M., Snell-Bergeon, J. K., Johnson, R. J., Nakagawa, T. 2015; 58 (9): 1993-2002

  Abstract

  Clinical studies have reported associations between serum uric acid levels and the development of diabetic nephropathy, but the underlying mechanisms remain elusive. There is evidence from animal studies that blocking uric acid production protects the kidney from tubulointerstitial injury, which may suggest a causal role for uric acid in the development of diabetic tubular injury. In turn, when fructose, which is endogenously produced in diabetes via the polyol pathway, is metabolised, uric acid is generated from a side-chain reaction driven by ATP depletion and purine nucleotide turnover. For this reason, uric acid derived from endogenous fructose could cause tubulointerstitial injury in diabetes. Accordingly, our research group recently demonstrated that blocking fructose metabolism in a diabetic mouse model mitigated the development of tubulointerstitial injury by lowering tubular uric acid production. In this review we discuss the relationship between uric acid and fructose as a novel mechanism for the development of diabetic tubular injury.

  View details for DOI 10.1007/s00125-015-3650-4

  View details for Web of Science ID 000359268800004

  View details for PubMedID 26049401

  View details for PubMedCentralID PMC4826347

• ISPAD Clinical Practice Consensus Guidelines 2014 Compendium: Type 2 diabetes in the child and adolescent (vol 15, pg 26, 2014) PEDIATRIC DIABETES Zeitler, P., Fu, J., Tandon, N., Nadeau, K., Urakami, T., Barrett, T., Maahs, D. 2015; 16 (5): 392-392

  View details for DOI 10.1111/pedi.12239

  View details for Web of Science ID 000357833800011

• Diagnosis and Prediction of CKD Progression by Assessment of Urinary Peptides JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY Schanstra, J. P., Zuerbig, P., Alkhalaf, A., Argiles, A., Bakker, S. J., Beige, J., Bilo, H. J., Chatzikyrkou, C., Dakna, M., Dawson, J., Delles, C., Haller, H., Haubitz, M., Husi, H., Jankowski, J., Jerums, G., Kleefstra, N., Kuznetsova, T., Maahs, D. M., Menne, J., Mullen, W., Ortiz, A., Persson, F., Rossing, P., Ruggenenti, P., Rychlik, I., Serra, A. L., Siwy, J., Snell-Bergeon, J., Spasovski, G., Staessen, J. A., Vlahou, A., Mischak, H., Vanholder, R. 2015; 26 (8): 1999-2010

  Abstract

  Progressive CKD is generally detected at a late stage by a sustained decline in eGFR and/or the presence of significant albuminuria. With the aim of early and improved risk stratification of patients with CKD, we studied urinary peptides in a large cross-sectional multicenter cohort of 1990 individuals, including 522 with follow-up data, using proteome analysis. We validated that a previously established multipeptide urinary biomarker classifier performed significantly better in detecting and predicting progression of CKD than the current clinical standard, urinary albumin. The classifier was also more sensitive for identifying patients with rapidly progressing CKD. Compared with the combination of baseline eGFR and albuminuria (area under the curve [AUC]=0.758), the addition of the multipeptide biomarker classifier significantly improved CKD risk prediction (AUC=0.831) as assessed by the net reclassification index (0.303±-0.065; P<0.001) and integrated discrimination improvement (0.058±0.014; P<0.001). Correlation of individual urinary peptides with CKD stage and progression showed that the peptides that associated with CKD, irrespective of CKD stage or CKD progression, were either fragments of the major circulating proteins, suggesting failure of the glomerular filtration barrier sieving properties, or different collagen fragments, suggesting accumulation of intrarenal extracellular matrix. Furthermore, protein fragments associated with progression of CKD originated mostly from proteins related to inflammation and tissue repair. Results of this study suggest that urinary proteome analysis might significantly improve the current state of the art of CKD detection and outcome prediction and that identification of the urinary peptides allows insight into various ongoing pathophysiologic processes in CKD.

  View details for DOI 10.1681/ASN.2014050423

  View details for Web of Science ID 000358895100024

  View details for PubMedID 25589610

  View details for PubMedCentralID PMC4520165

• Adiponectin-SOGA Dissociation in Type 1 Diabetes JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM Combs, T. P., Snell-Bergeon, J. K., Maahs, D. M., Bergman, B. C., Lamarche, M., Iberkleid, L., Abdelbaky, O., Tisch, R., Scherer, P. E., Marliss, E. B. 2015; 100 (8): E1065-E1073

  Abstract

  Circulating adiponectin is elevated in human type 1 diabetes (T1D) and nonobese diabetic (NOD) mice without the expected indications of adiponectin action, consistent with tissue resistance.Adiponectin stimulates hepatocyte production of the suppressor of glucose from autophagy (SOGA), a protein that inhibits glucose production. We postulated that due to tissue resistance, the elevation of adiponectin in T1D should fail to increase the levels of a surrogate marker for liver SOGA, the circulating C-terminal SOGA fragment.Liver and plasma SOGA were measured in NOD mice (n = 12) by Western blot. Serum adiponectin and SOGA were measured in T1D and control (Ctrl) participants undergoing a three-stage insulin clamp for the Coronary Artery Calcification in T1D study (n = 20). Glucose turnover was measured using 6,6[(2)H2]glucose (n = 12).In diabetic NOD mice, the 13%-29% decrease of liver SOGA (P = .003) and the 30%-37% reduction of circulating SOGA (P < .001) were correlated (r = 0.826; P = .001). In T1D serum, adiponectin was 50%-60% higher than Ctrl, SOGA was 30%-50% lower and insulin was 3-fold higher (P < .05). At the low insulin infusion rate (4 mU/m(2)·min), the resulting glucose appearance correlated negatively with adiponectin in T1D (r = -0.985, P = .002) and SOGA in Ctrl and T1D (r = -0.837, P = .001). Glucose disappearance correlated with adiponectin in Ctrl (r = -0.757, P = .049) and SOGA in Ctrl and T1D (r = -0.709, P = .010). At 40 mU/m(2)·min, the lowered glucose appearance was similar in Ctrl and T1D. Glucose disappearance increased only in Ctrl (P = .005), requiring greater glucose infusion to maintain euglycemia (8.58 ± 1.29 vs 3.09 ± 0.87 mg/kg·min; P = .009).The correlation between liver and plasma SOGA in NOD mice supports the use of the latter as surrogate marker for liver concentration. Reduced SOGA in diabetic NOD mice suggests resistance to adiponectin. The dissociation between adiponectin and SOGA in T1D raises the possibility that restoring adiponectin signaling and SOGA might improve the metabolic response to insulin therapy.

  View details for DOI 10.1210/jc.2015-1275

  View details for Web of Science ID 000364855900007

  View details for PubMedID 26052615

  View details for PubMedCentralID PMC4524989

• Predictive Low-Glucose Insulin Suspension Reduces Duration of Nocturnal Hypoglycemia in Children Without Increasing Ketosis DIABETES CARE Buckingham, B. A., Raghinaru, D., Cameron, F., Bequette, B. W., Chase, H. P., Maahs, D. M., Slover, R., Wadwa, R. P., Wilson, D. M., Ly, T., Aye, T., Hramiak, I., Clarson, C., Stein, R., Gallego, P. H., Lum, J., Sibayan, J., Kollman, C., Beck, R. W. 2015; 38 (7): 1197-1204

  Abstract

  Nocturnal hypoglycemia can cause seizures and is a major impediment to tight glycemic control, especially in young children with type 1 diabetes. We conducted an in-home randomized trial to assess the efficacy and safety of a continuous glucose monitor-based overnight predictive low-glucose suspend (PLGS) system.In two age-groups of children with type 1 diabetes (11-14 and 4-10 years of age), a 42-night trial for each child was conducted wherein each night was assigned randomly to either having the PLGS system active (intervention night) or inactive (control night). The primary outcome was percent time <70 mg/dL overnight.Median time at <70 mg/dL was reduced by 54% from 10.1% on control nights to 4.6% on intervention nights (P < 0.001) in 11-14-year-olds (n = 45) and by 50% from 6.2% to 3.1% (P < 0.001) in 4-10-year-olds (n = 36). Mean overnight glucose was lower on control versus intervention nights in both age-groups (144 ± 18 vs. 152 ± 19 mg/dL [P < 0.001] and 153 ± 14 vs. 160 ± 16 mg/dL [P = 0.004], respectively). Mean morning blood glucose was 159 ± 29 vs. 176 ± 28 mg/dL (P < 0.001) in the 11-14-year-olds and 154 ± 25 vs. 158 ± 22 mg/dL (P = 0.11) in the 4-10-year-olds, respectively. No differences were found between intervention and control in either age-group in morning blood ketosis.In 4-14-year-olds, use of a nocturnal PLGS system can substantially reduce overnight hypoglycemia without an increase in morning ketosis, although overnight mean glucose is slightly higher.

  View details for DOI 10.2337/dc14-3053

  View details for PubMedID 26049549

• Association of apolipoprotein B, LDL-C and vascular stiffness in adolescents with type 1 diabetes ACTA DIABETOLOGICA Bjornstad, P., Nhung Nguyen, N., Reinick, C., Maahs, D. M., Bishop, F. K., Clements, S. A., Snell-Bergeon, J. K., Lieberman, R., Pyle, L., Daniels, S. R., Wadwa, R. P. 2015; 52 (3): 611-619

  Abstract

  LDL cholesterol (LDL-C) is the current lipid standard for cardiovascular disease (CVD)-risk assessment in type 1 diabetes. Apolipoprotein B (apoB) may be helpful to further stratify CVD risk. We explored the association between apoB and pulse wave velocity (PWV) to determine if apoB would improve CVD-risk stratification, especially in type 1 diabetes adolescents with borderline LDL-C (100-129 mg/dL). We hypothesized that type 1 diabetes adolescents with borderline LDL-C and elevated apoB (?90 mg/dL) would have increased PWV compared to those with borderline LDL-C and normal apoB (<90 mg/dL), and that apoB would explain more of the variability of PWV than alternative lipid indices.Fasting lipids, including apoB, were collected in 267 adolescents, age 12-19 years, with diabetes duration >5 years and HbA1c 8.9 ± 1.6 %. Triglyceride to HDL-C ratio (TG/HDL-C) and nonHDL-cholesterol (nonHDL-C) were calculated. PWV was measured in the carotid-femoral segment.ApoB, nonHDL-C and TG/HDL-C correlated with PWV (p < 0.0001). ApoB, nonHDL-C and TG/HDL-C remained significantly associated with PWV in fully adjusted models. In adolescents with borderline LDL-C (n = 61), PWV was significantly higher in those with elevated apoB than in those with normal apoB (5.6 ± 0.6 vs. 5.2 ± 0.6 m/s, p < 0.01) and also remained significant after adjustment for CVD-risk factors (p = 0.0002). Moreover, in those with borderline LDL-C, apoB explained more of the variability of PWV than nonHDL-C and TG/HDL-C.Elevated apoB is associated with increased arterial stiffness in type 1 diabetes adolescents. Measurement of apoB in addition to LDL-C may be helpful in stratifying CVD risk in type 1 diabetes adolescents, especially in those with borderline LDL-C.

  View details for DOI 10.1007/s00592-014-0693-9

  View details for Web of Science ID 000355233500021

  View details for PubMedID 25539881

  View details for PubMedCentralID PMC4449793

• Diabetes Complications in Childhood Diabetes-New Biomarkers and Technologies. Current pediatrics reports Bjornstad, P., Maahs, D. M. 2015; 3 (2): 177-186

  Abstract

  A major challenge in preventing vascular complications in diabetes is the inability to identify high-risk patients at an early stage, emphasizing the importance of discovering new risk factors, technologies and therapeutic targets to reduce the development and progression of complications. Promising biomarkers which may improve risk stratification and serve as therapeutic targets, include: uric acid, insulin sensitivity, copeptin, SGLT-2 and Klotho/FGF-23. Non-invasive measures of macrovasuclar disease in youth, include: 1) pulse wave velocity to examine arterial stiffness; 2) carotid intima-media thickness to evaluate arterial thickness; 3) cardiac MRI to investigate cardiac function and structure. Novel microvascular measures include: GFR by iohexol clearance using filter paper to directly measure GFR, retinal vascular geometry to predict early retinal changes and corneal confocal microscopy to improve detection of early nerve loss to better predict diabetic neuropathy. Herein we will review technologies, novel biomarkers, and therapeutic targets in relation to vascular complications of diabetes.

  View details for PubMedID 26425403

• Factors Associated with Nocturnal Hypoglycemia in At-Risk Adolescents and Young Adults with Type 1 Diabetes DIABETES TECHNOLOGY & THERAPEUTICS Wilson, D. M., Calhoun, P. M., Maahs, D. M., Chase, H. P., Messer, L., Buckingham, B. A., Aye, T., Clinton, P. K., Hramiak, I., Kollman, C., Beck, R. W. 2015; 17 (6): 385-391

  Abstract

  Hypoglycemia remains an impediment to good glycemic control, with nocturnal hypoglycemia being particularly dangerous. Information on major contributors to nocturnal hypoglycemia remains critical for understanding and mitigating risk.Continuous glucose monitoring (CGM) data for 855 nights were studied, generated by 45 subjects 15-45 years of age with hemoglobin A1c (HbA1c) levels of ?8.0% who participated in a larger randomized study. Factors assessed for potential association with nocturnal hypoglycemia (CGM measurement of <60?mg/dL for ?30?min) included bedtime blood glucose (BG), exercise intensity, bedtime snack, insulin on board, day of the week, previous daytime hypoglycemia, age, gender, HbA1c level, diabetes duration, daily basal insulin, and daily insulin dose.Hypoglycemia occurred during 221 of 885 (25%) nights and was more frequent with younger age (P<0.001), lower HbA1c levels (P=0.006), medium/high-intensity exercise during the preceding day (P=0.003), and the occurrence of antecedent daytime hypoglycemia (P=0.001). There was a trend for lower bedtime BG levels to be associated with more frequent nocturnal hypoglycemia (P=0.10). Bedtime snack, before bedtime insulin bolus, weekend versus weekday, gender, and daily basal and bolus insulin were not associated with nocturnal hypoglycemia.Awareness that HbA1c level, exercise, bedtime BG level, and daytime hypoglycemia are all modifiable factors associated with nocturnal hypoglycemia may help patients and providers decrease the risk of hypoglycemia at night. Risk for nocturnal hypoglycemia increased in a linear fashion across the range of variables, with no clear-cut thresholds to guide clinicians or patients for any particular night.

  View details for DOI 10.1089/dia.2014.0342

  View details for PubMedID 25761202

• Flexible Lifestyles for Youth (FL3X) behavioural intervention for at-risk adolescents with Type 1 diabetes: a randomized pilot and feasibility trial DIABETIC MEDICINE Mayer-Davis, E. J., Seid, M., CRANDELL, J., Dolan, L., Lagarde, W. H., Letourneau, L., Maahs, D. M., Marcovina, S., Nachreiner, J., Standiford, D., Thomas, J., Wysocki, T. 2015; 32 (6): 829-833

  Abstract

  To determine the potential effect sizes for the Flexible Lifestyle for Youth (FL3X) behavioural intervention to improve glycaemic control (HbA(1c)) and quality of life for at-risk adolescents with Type 1 diabetes.Participants [n = 61; age 12-16 years, HbA(1c) 64-119 mmol/mol (8-13%)] were randomized to FL3X (minimum three sessions) or usual care. Effect sizes (Cohen's d), comparing the mean difference between the groups, were calculated.Study retention (95%), attendance at intervention sessions (87% attended all three sessions) and acceptability were high (100% of the adolescents and 91% of parents would recommend the programme to others). Overall, 41% of participants in the intervention group and 24% of participants in the control group were 'responders' [HbA(1c) decreased by > 6 mmol/mol (0.5%); d = 0.37]. HbA(1c) levels decreased (d = -0.18), diabetes-specific quality of life increased (d = 0.29), but generic quality of life decreased (d = -0.23) in the intervention compared with the control group.The FL3X programme merits further study for improving HbA(1c) and diabetes-specific quality of life in adolescents with Type 1 diabetes. (Clinical trials registry no.: NCT01286350).

  View details for DOI 10.1111/dme.12641

  View details for Web of Science ID 000354637600019

  View details for PubMedID 25424501

  View details for PubMedCentralID PMC4437823

• Current State of Type 1 Diabetes Treatment in the US: Updated Data From the T1D Exchange Clinic Registry DIABETES CARE Miller, K. M., Foster, N. C., Beck, R. W., Bergenstal, R. M., DuBose, S. N., Dimeglio, L. A., Maahs, D. M., Tamborlane, W. V. 2015; 38 (6): 971-978

  Abstract

  To examine the overall state of metabolic control and current use of advanced diabetes technologies in the U.S., we report recent data collected on individuals with type 1 diabetes participating in the T1D Exchange clinic registry. Data from 16,061 participants updated between 1 September 2013 and 1 December 2014 were compared with registry enrollment data collected from 1 September 2010 to 1 August 2012. Mean hemoglobin A1c (HbA1c) was assessed by year of age from <4 to >75 years. The overall average HbA1c was 8.2% (66 mmol/mol) at enrollment and 8.4% (68 mmol/mol) at the most recent update. During childhood, mean HbA1c decreased from 8.3% (67 mmol/mol) in 2-4-year-olds to 8.1% (65 mmol/mol) at 7 years of age, followed by an increase to 9.2% (77 mmol/mol) in 19-year-olds. Subsequently, mean HbA1c values decline gradually until ?30 years of age, plateauing at 7.5-7.8% (58-62 mmol/mol) beyond age 30 until a modest drop in HbA1c below 7.5% (58 mmol/mol) in those 65 years of age. Severe hypoglycemia (SH) and diabetic ketoacidosis (DKA) remain all too common complications of treatment, especially in older (SH) and younger patients (DKA). Insulin pump use increased slightly from enrollment (58-62%), and use of continuous glucose monitoring (CGM) did not change (7%). Although the T1D Exchange registry findings are not population based and could be biased, it is clear that there remains considerable room for improving outcomes of treatment of type 1 diabetes across all age-groups. Barriers to more effective use of current treatments need to be addressed and new therapies are needed to achieve optimal metabolic control in people with type 1 diabetes.

  View details for DOI 10.2337/dc15-0078

  View details for Web of Science ID 000362969000015

  View details for PubMedID 25998289

• Change in adiposity minimally affects the lipid profile in youth with recent onset type 1 diabetes PEDIATRIC DIABETES Shah, A. S., Dolan, L. M., Dabelea, D., Stafford, J. M., D'Agostino, R. B., Mayer-Davis, E. J., Marcovina, S., Imperatore, G., Wadwa, R. P., Daniels, S. R., Reynolds, K., Hamman, R. F., Bowlby, D. A., Maahs, D. M. 2015; 16 (4): 280-286

  Abstract

  Dyslipidemia contributes to the increased risk of cardiovascular disease in persons with type 1 diabetes (T1D). Weight control is commonly recommended as a treatment for dyslipidemia. However, the extent to which decreases in weight affect the lipid profile in youth with T1D is not known. Therefore, we tested the hypothesis that decreases in body mass index z-score (BMIz) were associated with concomitant changes in the lipid profile in youth with T1D.We studied 1142 youth with incident T1D, who had at least two fasting lipid measurements over 2 yr (initial visit mean: age = 10.8 ± 3.9 yr, BMIz = 0.55 ± 0.97, T1D duration = 10.7 ± 7.6 months; 47.5% female, 77.9% non-Hispanic white) in the SEARCH for Diabetes in Youth Study. Longitudinal mixed models were used to examine the relationships between changes in BMIz and changes in total, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), non-HDL cholesterol, and log triglycerides (TG) adjusted for initial age, sex, race/ethnicity, clinical site, season of study visit, T1D duration, and glycated hemoglobin A1c (HbA1c).We found that over 2 yr all lipid levels, except LDL-C, increased significantly (p < 0.05). Decreases in BMIz were associated with favorable changes in HDL-C and TG only and the magnitude of these changes depended on the initial BMIz value (interaction p < 0.05), so that greater improvements were seen in those with higher BMIz.Our data suggest that weight loss may be an effective, but limited, therapeutic approach for dyslipidemia in youth with T1D.

  View details for DOI 10.1111/pedi.12162

  View details for Web of Science ID 000354123300006

  View details for PubMedID 25099744

  View details for PubMedCentralID PMC4320680

• Refining the Closed Loop in the Data Age: Research-to-Practice Transitions in Diabetes Technology DIABETES TECHNOLOGY & THERAPEUTICS Forlenza, G. P., Sankaranarayanan, S., Maahs, D. M. 2015; 17 (5): 304-306

  View details for DOI 10.1089/dia.2015.0055

  View details for Web of Science ID 000353485700002

  View details for PubMedID 25844981

• Response to comment on Wong et al. Real-time continuous glucose monitoring among participants in the T1D exchange clinic registry. Diabetes Care 2014;37:2702-2709. Diabetes care Wong, J. C., Foster, N. C., Maahs, D. M., Raghinaru, D., Bergenstal, R. M., Ahmann, A. J., Peters, A. L., Bode, B. W., Aleppo, G., Hirsch, I. B., Kleis, L., Chase, H. P., DuBose, S. N., Miller, K. M., Beck, R. W., Adi, S. 2015; 38 (4)

  View details for DOI 10.2337/dc14-2782

  View details for PubMedID 25805875

• DIABETES Elevated risk of mortality in type 1 diabetes mellitus NATURE REVIEWS ENDOCRINOLOGY Snell-Bergeon, J. K., Maahs, D. M. 2015; 11 (3): 136-137

  View details for DOI 10.1038/nrendo.2014.245

  View details for Web of Science ID 000349892000004

  View details for PubMedID 25583696

• Insulin sensitivity and complications in type 1 diabetes: New insights. World journal of diabetes Bjornstad, P., Snell-Bergeon, J. K., Nadeau, K. J., Maahs, D. M. 2015; 6 (1): 8-16

  Abstract

  Despite improvements in glucose, lipids and blood pressure control, vascular complications remain the most important cause of morbidity and mortality in patients with type 1 diabetes. For that reason, there is a need to identify additional risk factors to utilize in clinical practice or translate to novel therapies to prevent vascular complications. Reduced insulin sensitivity is an increasingly recognized component of type 1 diabetes that has been linked with the development and progression of both micro- and macrovascular complications. Adolescents and adults with type 1 diabetes have reduced insulin sensitivity, even when compared to their non-diabetic counterparts of similar adiposity, serum triglycerides, high-density lipoprotein cholesterol, level of habitual physical activity, and in adolescents, pubertal stage. Reduced insulin sensitivity is thought to contribute both to the initiation and progression of macro- and microvascular complications in type 1 diabetes. There are currently clinical trials underway examining the benefits of improving insulin sensitivity with regards to vascular complications in type 1 diabetes. Reduced insulin sensitivity is an increasingly recognized component of type 1 diabetes, is implicated in the pathogenesis of vascular complications and is potentially an important therapeutic target to prevent vascular complications. In this review, we will focus on the pathophysiologic contribution of insulin sensitivity to vascular complications and summarize related ongoing clinical trials.

  View details for DOI 10.4239/wjd.v6.i1.8

  View details for PubMedID 25685274

  View details for PubMedCentralID PMC4317319

• Achieving International Society for Pediatric and Adolescent Diabetes and American Diabetes Association clinical guidelines offers cardiorenal protection for youth with type 1 diabetes. Pediatric diabetes Bjornstad, P., Pyle, L., Nguyen, N., Snell-Bergeon, J. K., Bishop, F. K., Wadwa, R. P., Maahs, D. M. 2015; 16 (1): 22-30

  Abstract

  Most youth with type 1 diabetes do not meet the American Diabetes Association (ADA) and International Society for Pediatric and Adolescent Diabetes (ISPAD) targets for hemoglobin A1c (HbA1c), blood pressure (BP), lipids, and body mass index (BMI). We hypothesized that ISPAD/ADA goal achievement at baseline would be associated with cardiorenal risk factors at baseline and 2 yr follow-up in adolescents with type 1 diabetes.We assessed the cross-sectional and longitudinal relationships between ISPAD/ADA goal achievement at baseline and cardiorenal health at baseline and 2-yr follow-up (n = 297; 15.4 ± 2.1 yr at baseline) in adolescents with type 1 diabetes. Goal achievement was defined as HbA1c < 7.5%, BP < 90th percentile for age, sex, and height, low density lipoprotein-cholesterol (LDL-C) <100 mg/dL, high density lipoprotein-cholesterol (HDL-C) >35 mg/dL, triglycerides (TG) <150 mg/dL and BMI <85th percentile for age and sex. Cardiorenal outcomes included pulse-wave velocity (PWV), brachial distensibility (BrachD), augmentation index (AIx), and epidermal growth factor receptor (eGFR) continuously and categorically as hyperfiltration (eGFR ? 135 mL/min/1.73 m(2)).Adolescents with type 1 diabetes who met 1-3 goals, had significantly greater (P < 0.05) baseline PWV (5.1 ± 0.1 vs. 5.4 ± 0.1 m/s), follow-up PWV (5.5 ± 0.1 vs. 5.7 ± 0.1 m/s), greater follow-up eGFR (104 ± 2 vs. 116 ± 3 mL/min/1.73 m(2)), and greater odds of renal hyperfiltration at follow-up (odds ratio (OR): 20.0, 95% confidence interval (CI): 3.8-105.2) compared to those who met 4-6 goals after adjusting for Tanner stage, sex, age, and diabetes duration. No statistically significant differences in the cardiorenal outcomes were observed between adolescents with type 1 diabetes who met 4-6 goals and non-diabetic controls (n = 96).In adolescents with type 1 diabetes, baseline ADA/ISPAD goal achievement was associated with cardiorenal protection at baseline and 2-yr follow-up.

  View details for DOI 10.1111/pedi.12252

  View details for PubMedID 25604668

• Achieving International Society for Pediatric and Adolescent Diabetes and American Diabetes Association clinical guidelines offers cardiorenal protection for youth with type 1 diabetes PEDIATRIC DIABETES Bjornstad, P., Pyle, L., Nhung Nguyen, N., Snell-Bergeon, J. K., Bishop, F. K., Wadwa, R. P., Maahs, D. M. 2015; 16 (1): 22-30

  View details for DOI 10.1111/pedi.12252

  View details for Web of Science ID 000348768500004

• Estimated insulin sensitivity predicts regression of albuminuria in Type 1 diabetes DIABETIC MEDICINE Bjornstad, P., Maahs, D. M., JOHNSON, R. J., Rewers, M., Snell-Bergeon, J. K. 2015; 32 (2): 257-261

  Abstract

  To test the hypothesis that greater baseline insulin sensitivity would predict regression of albuminuria over 6 years in adults with Type 1 diabetes.We enrolled 81 people aged 30-48 years with albuminuria at baseline in the present study and re-examined them 6 years later. Urinary albumin excretion rate was measured and albuminuria was defined as urinary albumin excretion rate ? 20 ?g/min. Regression of albuminuria was defined as normoalbuminuria (urinary albumin excretion rate < 20 ?g/min) at follow-up. Predictors of regression of albuminuria were examined in stepwise logistic regression. The variables age, diabetes duration, sex, serum uric acid, HbA1c , systolic blood pressure, LDL cholesterol, HDL cholesterol, BMI, baseline albumin excretion rate, estimated insulin sensitivity at baseline, change in estimated insulin sensitivity from baseline to follow-up and angiotensin-converting enzyme inhibitor/angiotensin receptor blocker use were considered for inclusion in the model.Estimated insulin sensitivity was significantly higher at both baseline (4.6 ± 1.2 vs 3.4 ± 1.7; P = 0.002) and follow-up (5.2 ± 1.9 vs. 3.5 ± 1.7; P < 0.0001) in people who had regression of albuminuria vs those who did not. HbA1c (odds ratio 0.4, 95% CI 0.2-0.8; P = 0.006), estimated insulin sensitivity (odds ratio 2.5, 95% CI 1.3-4.9; P = 0.006) at baseline and change in estimated insulin sensitivity from baseline to follow-up (odds ratio 2.7, 95% CI 1.4-5.3; P = 0.003) were independently associated with regression of albuminuria in a multivariable stepwise model.In conclusion, over 6 years, higher baseline estimated insulin sensitivity and change in estimated insulin sensitivity independently predicted regression of albuminuria. Improving insulin sensitivity in people with Type 1 diabetes is a potential therapeutic target to increase rates of regression of albuminuria.

  View details for DOI 10.1111/dme.12572

  View details for Web of Science ID 000348515500017

  View details for PubMedID 25303233

  View details for PubMedCentralID PMC4301993

• Renal Function Is Associated With Peak Exercise Capacity in Adolescents With Type 1 Diabetes DIABETES CARE Bjornstad, P., Cree-Green, M., Baumgartner, A., Maahs, D. M., Cherney, D. Z., Pyle, L., Regensteiner, J. G., Reusch, J. E., Nadeau, K. J. 2015; 38 (1): 126-131

  Abstract

  Diabetic nephropathy and cardiovascular disease are strongly related in adults with type 1 diabetes, yet little is known about this relationship in adolescents prior to the onset of detectable clinical disease. We hypothesized that cardiopulmonary fitness would be directly associated with albumin-to-creatinine ratio (ACR) and inversely related to estimated glomerular filtration rate (eGFR) in adolescents with type 1 diabetes.Sixty-nine adolescents with type 1 diabetes and 13 nondiabetic control subjects of similar pubertal stage and BMI had insulin sensitivity (glucose infusion rate [GIR]), measured by hyperinsulinemic-euglycemic clamp, and lean body mass, measured by DEXA. Cardiopulmonary fitness was measured by cycle ergometry to obtain peak volume of oxygen (VO2peak), and renal function was measured by eGFR using the Bouvet equation (measuring creatinine and cystatin C levels) and ACR.Adolescents (15.5 ± 2.2 years of age) with type 1 diabetes (6.3 ± 3.8 years diabetes duration) had reduced VO2peak (31.5 ± 6.3 vs. 36.2 ± 7.9 mL/kg ? min, P = 0.046) and VO2peak/lean kg (43.7 ± 7.0 vs. 51.0 ± 8.6 mL/lean kg ? min, P = 0.007) compared with nondiabetic control subjects. eGFR was inversely associated with VO2peak and VO2peak/lean kg after adjusting for sex, Tanner stage, GIR, HbA1c level, systolic blood pressure, and LDL cholesterol level (? ± SE, VO2peak: -0.19 ± 0.07, P = 0.02; VO2peak/lean kg: -0.19 ± 0.09, P = 0.048). Moreover, participants in the highest tertile for eGFR had significantly lower sex- and Tanner-adjusted VO2peak and VO2peak/lean kg compared with participants in the lowest tertile.Adolescents with type 1 diabetes had reduced exercise capacity, which was strongly associated with renal health, independent of insulin sensitivity. Future studies should examine the underlying interrelated pathophysiology in order to identify probable targets for treatment to reduce cardiovascular and renal complications.

  View details for DOI 10.2337/dc14-1742

  View details for Web of Science ID 000346762300024

  View details for PubMedID 25414156

  View details for PubMedCentralID PMC4274775

• Fat Mass Is Associated With Cystatin C and Estimated Glomerular Filtration Rate in Adolescents With Type 1 Diabetes. Journal of renal nutrition : the official journal of the Council on Renal Nutrition of the National Kidney Foundation Bjornstad, P., Cherney, D. Z., Maahs, D. M., Nadeau, K. J. 2015; 25 (5): 454?55

  View details for PubMedID 26028175

  View details for PubMedCentralID PMC5846471

• Towards a Verified Artificial Pancreas: Challenges and Solutions for Runtime Verification RUNTIME VERIFICATION, RV 2015 Cameron, F., Fainekos, G., Maahs, D. M., Sankaranarayanan, S. 2015; 9333: 3-17

  View details for DOI 10.1007/978-3-319-23820-3_1

  View details for Web of Science ID 000370624400001

• Plasma triglycerides predict incident albuminuria and progression of coronary artery calcification in adults with type 1 diabetes: The Coronary Artery Calcification in Type 1 Diabetes Study JOURNAL OF CLINICAL LIPIDOLOGY Bjornstad, P., Maahs, D. M., Wadwa, R. P., Pyle, L., Rewers, M., Eckel, R. H., Snell-Bergeon, J. K. 2014; 8 (6): 576-583

  Abstract

  Coronary artery disease and diabetic nephropathy, which are thought to share pathogenic mechanisms, remain the most common causes of mortality in type 1 diabetes (T1D). Data from basic and clinical studies indicate that hypertriglyceridemia plays an important role in the pathogenesis of vascular complications, but the role of triglycerides (TG) in the normal range remains unresolved in T1D.We hypothesized that fasting TG would independently predict cardiorenal disease in adults with T1D and normal-to-low levels of TG.Subjects (N = 652) were 19 to 56 years old at baseline and reexamined 6 years later. Urinary albumin excretion was measured, and categorized as microalbuminuria or greater. Progression of coronary artery calcification (CACp), measured using electron beam computed tomography, was defined as a change in the square root transformed CAC volume ?2.5. The association of low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), apolipoprotein B, non-HDL-C, natural log triglyceride (lnTG), ln(TG/HDL-C) ratio with CACp and incident albuminuria were examined in logistic regression. The models were adjusted for age, sex, T1D duration, hemoglobin A1c, systolic blood pressure, diastolic blood pressure, blood pressure medications, statins, and smoking status. Integrated discrimination index and net reclassification improvement were used to examine prediction performance.Incident albuminuria was independently associated with CACp. lnTG independently predicted both incident albuminuria (odds ratio: 1.53, 1.02-2.30, P = .04) and CACp (1.41, 1.11-1.80, P = .006). The addition of lnTG to ABC risk factors (HbA1c, systolic blood pressure, diastolic blood pressure, and LDL-C) moderately improved discrimination and reclassification of CACp and incident albuminuria.In adults with T1D, fasting TG independently predicted cardiorenal disease over 6 years and improved reclassification of risk by conventional risk factors.

  View details for DOI 10.1016/j.jacl.2014.08.008

  View details for Web of Science ID 000346880900008

  View details for PubMedID 25499940

  View details for PubMedCentralID PMC4268486

• Insulin Sensitivity Is an Important Determinant of Renal Health in Adolescents With Type 2 Diabetes DIABETES CARE Bjornstad, P., Maahs, D. M., Cherney, D. Z., Cree-Green, M., West, A., Pyle, L., Nadeau, K. J. 2014; 37 (11): 3033-3039

  Abstract

  Diabetic nephropathy (DN) remains the most common cause of end-stage renal disease and is a major cause of mortality in type 2 diabetes. Insulin sensitivity is an important determinant of renal health in adults with type 2 diabetes, but limited data exist in adolescents. We hypothesized that measured insulin sensitivity (glucose infusion rate [GIR]) would be associated with early markers of DN reflected by estimated glomerular filtration rate (eGFR) and albumin-creatinine ratio (ACR) in adolescents with type 2 diabetes.Type 2 diabetic (n = 46), obese (n = 29), and lean (n = 19) adolescents (15.1 ± 2.2 years) had GIR measured by hyperinsulinemic-euglycemic clamps. ACR was measured and GFR was estimated by the Bouvet equation (combined creatinine and cystatin C).Adolescents with type 2 diabetes had significantly lower GIR, and higher eGFR and ACR than obese or lean adolescents. Moreover, 34% of type 2 diabetic adolescents had albuminuria (ACR ?30 mg/g), and 24% had hyperfiltration (?135 mL/min/1.73 m2). Stratifying ACR and eGFR into tertiles, adolescents with type 2 diabetes in the highest tertiles of ACR and eGFR had respectively lower GIR than those in the mid and low tertiles, after adjusting for age, sex, Tanner stage, BMI, and HbA1c (P = 0.02 and P = 0.04). GIR, but not HbA1c, LDL, or systolic blood pressure, was also associated with eGFR after adjusting for sex and Tanner stage (? ± SE: -2.23 ± 0.87; P = 0.02).A significant proportion of adolescents with type 2 diabetes showed evidence of early DN, and insulin sensitivity, rather than HbA1c, blood pressure, or lipid control, was the strongest determinant of renal health.

  View details for DOI 10.2337/dc14-1331

  View details for Web of Science ID 000343588500032

  View details for PubMedID 25071077

  View details for PubMedCentralID PMC4207204

• ABC goal achievement predicts microvascular but not macrovascular complications over 6-years in adults with type 1 diabetes: The Coronary Artery Calcification in Type 1 Diabetes Study JOURNAL OF DIABETES AND ITS COMPLICATIONS Bjornstad, P., Maahs, D. M., Rewers, M., Johnson, R. J., Snell-Bergeon, J. K. 2014; 28 (6): 762-766

  Abstract

  Vascular complications of type 1 diabetes are thought to cluster. We examined the prevalence and incidence of vascular complications and American Diabetes Association's ABC goal achievements in a prospective cohort of adults with type 1 diabetes. We hypothesized that ABC achievement at baseline would predict both micro- and macrovascular complications over 6-years.Participants (N=652) were 19-56 year old at baseline and re-examined 6-years later. Microvascular complications included diabetic nephropathy (DN), defined as incident albuminuria (AER?20 ?g/min) or rapid GFR decline (>3.3%/year) by CKD-EPI cystatin C and proliferative diabetic retinopathy (PDR), defined as laser eye-therapy. Macrovascular complications were defined as coronary artery calcium progression (CACp), measured by electron-beam computed-tomography. ABC goals were defined as HbA1c<7.0%, BP<130/80 mmHg and LDL-C<100mg/dL.ABC control was suboptimal with only 6% meeting all goals. Meeting no ABC goals at baseline compared to meeting all goals was associated with increased odds of developing microvascular complications (OR: 8.5, 2.3-31.5, p=0.001), but did not reach significance for CACp (OR: 1.7, 0.8-3.9, p=0.19).ABC achievement at baseline strongly predicted microvascular but not macrovascular complications over 6-years in adults with type 1 diabetes, suggesting a need for novel therapeutic targets to complement conventional risk factors in treating macrovascular complications.

  View details for DOI 10.1016/j.jdiacomp.2014.06.017

  View details for Web of Science ID 000344981200004

  View details for PubMedID 25270733

  View details for PubMedCentralID PMC4252593

• A novel method to detect pressure-induced sensor attenuations (PISA) in an artificial pancreas. Journal of diabetes science and technology Baysal, N., Cameron, F., Buckingham, B. A., Wilson, D. M., Chase, H. P., Maahs, D. M., Bequette, B. W. 2014; 8 (6): 1091-1096

  Abstract

  Continuous glucose monitors (CGMs) provide real-time interstitial glucose concentrations that are essential for automated treatment of individuals with type 1 diabetes. Miscalibration, noise spikes, dropouts, or pressure applied to the site (e.g., lying on the site while sleeping) can cause inaccurate glucose signals, which could lead to inappropriate insulin dosing decisions. These studies focus on the problem of pressure-induced sensor attenuations (PISAs) that occur overnight and can cause undesirable pump shut-offs in a predictive low glucose suspend system. The algorithm presented here uses real-time CGM readings without knowledge of meals, insulin doses, activity, sensor recalibrations, or fingerstick measurements. The real-time PISA detection technique was tested on outpatient "in-home" data from a predictive low-glucose suspend trial with over 1125 nights of data. A total of 178 sets were created by using different parameters for the PISA detection algorithm to illustrate its range of available performance. The tracings were reviewed via a web-based analysis tool by an engineer with an extensive expertise on analyzing clinical datasets and ~3% of the CGM readings were marked as PISA events which were used as the gold standard. It is shown that 88.34% of the PISAs were successfully detected by the algorithm, and the percentage of false detections could be reduced to 1.70% by altering the algorithm parameters. Use of the proposed PISA detection method can result in a significant decrease in undesirable pump suspensions overnight, and may lead to lower overnight mean glucose levels while still achieving a low risk of hypoglycemia.

  View details for DOI 10.1177/1932296814553267

  View details for PubMedID 25316716

• Predicting major outcomes in type 1 diabetes: a model development and validation study DIABETOLOGIA Soedamah-Muthu, S. S., Vergouwe, Y., Costacou, T., Miller, R. G., Zgibor, J., Chaturvedi, N., Snell-Bergeon, J. K., Maahs, D. M., Rewers, M., Forsblom, C., Harjutsalo, V., Groop, P., Fuller, J. H., Moons, K. G., Orchard, T. J. 2014; 57 (11): 2304-2314

  Abstract

  Type 1 diabetes is associated with a higher risk of major vascular complications and death. A reliable method that predicted these outcomes early in the disease process would help in risk classification. We therefore developed such a prognostic model and quantified its performance in independent cohorts.Data were analysed from 1,973 participants with type 1 diabetes followed for 7 years in the EURODIAB Prospective Complications Study. Strong prognostic factors for major outcomes were combined in a Weibull regression model. The performance of the model was tested in three different prospective cohorts: the Pittsburgh Epidemiology of Diabetes Complications study (EDC, n?=?554), the Finnish Diabetic Nephropathy study (FinnDiane, n?=?2,999) and the Coronary Artery Calcification in Type 1 Diabetes study (CACTI, n?=?580). Major outcomes included major CHD, stroke, end-stage renal failure, amputations, blindness and all-cause death.A total of 95 EURODIAB patients with type 1 diabetes developed major outcomes during follow-up. Prognostic factors were age, HbA1c, WHR, albumin/creatinine ratio and HDL-cholesterol level. The discriminative ability of the model was adequate, with a concordance statistic (C-statistic) of 0.74. Discrimination was similar or even better in the independent cohorts, the C-statistics being: EDC, 0.79; FinnDiane, 0.82; and CACTI, 0.73.Our prognostic model, which uses easily accessible clinical features can discriminate between type 1 diabetes patients who have a good or a poor prognosis. Such a prognostic model may be helpful in clinical practice and for risk stratification in clinical trials.

  View details for DOI 10.1007/s00125-014-3358-x

  View details for Web of Science ID 000344630300007

  View details for PubMedID 25186291

  View details for PubMedCentralID PMC4399797

• Cardiovascular Disease Risk Factors in Youth With Diabetes Mellitus A Scientific Statement From the American Heart Association CIRCULATION Maahs, D. M., Daniels, S. R., de Ferranti, S. D., Dichek, H. L., Flynn, J., Goldstein, B. I., Kelly, A. S., Nadeau, K. J., Martyn-Nemeth, P., Osganian, S. K., Quinn, L., Shah, A. S., Urbina, E. 2014; 130 (17): 1532-U224

  View details for DOI 10.1161/CIR.0000000000000094

  View details for Web of Science ID 000344064500019

  View details for PubMedID 25170098

• Multicenter Closed-Loop/Hybrid Meal Bolus Insulin Delivery with Type 1 Diabetes DIABETES TECHNOLOGY & THERAPEUTICS Chase, H. P., Doyle, F. J., Zisser, H., Renard, E., Nimri, R., Cobelli, C., Buckingham, B. A., Maahs, D. M., Anderson, S., Magni, L., Lum, J., Calhoun, P., Kollman, C., Beck, R. W. 2014; 16 (10): 623-632

  Abstract

  This study evaluated meal bolus insulin delivery strategies and associated postprandial glucose control while using an artificial pancreas (AP) system.This study was a multicenter trial in 53 patients, 12-65 years of age, with type 1 diabetes for at least 1 year and use of continuous subcutaneous insulin infusion for at least 6 months. Four different insulin bolus strategies were assessed: standard bolus delivered with meal (n=51), standard bolus delivered 15 min prior to meal (n=40), over-bolus of 30% delivered with meal (n=40), and bolus purposely omitted (n=46). Meal carbohydrate (CHO) intake was 1 g of CHO/kg of body weight up to a maximum of 100 g for the first three strategies or up to a maximum of 50 g for strategy 4.Only three of 177 meals (two with over-bolus and one with standard bolus 15 min prior to meal) had postprandial blood glucose values of <60 mg/dL. Postprandial hyperglycemia (blood glucose level >180 mg/dL) was prolonged for all four bolus strategies but was shorter for the over-bolus (41% of the 4-h period) than the two standard bolus strategies (73% for each). Mean postprandial blood glucose level was 15.9 mg/dL higher for the standard bolus with meal compared with the prebolus (baseline-adjusted, P=0.07 for treatment effect over the 4-h period).The AP handled the four bolus situations safely, but at the expense of having elevated postprandial glucose levels in most subjects. This was most likely secondary to suboptimal performance of the algorithm.

  View details for DOI 10.1089/dia.2014.0050

  View details for Web of Science ID 000342561100003

  View details for PubMedID 25188375

  View details for PubMedCentralID PMC4183919

• Serum uric acid predicts vascular complications in adults with type 1 diabetes: the coronary artery calcification in type 1 diabetes study ACTA DIABETOLOGICA Bjornstad, P., Maahs, D. M., Rivard, C. J., Pyle, L., Rewers, M., Johnson, R. J., Snell-Bergeon, J. K. 2014; 51 (5): 783-791

  Abstract

  Epidemiologic evidence supports a link between serum uric acid (SUA) and vascular complications in diabetes, but it remains unclear whether SUA improves the ability of conventional risk factor to predict complications. We hypothesized that SUA at baseline would independently predict the development of vascular complications over 6 years and that the addition of SUA to American Diabetes Association's ABC risk factors (HbA1c, BP, LDL-C) would improve vascular complication prediction over 6 years in adults with type 1 diabetes. Study participants (N = 652) were 19-56 year old at baseline and re-examined 6 years later. Diabetic nephropathy was defined as incident albuminuria or rapid GFR decline (>3.3 %/year) estimated by the CKD-EPI cystatin C. Diabetic retinopathy (DR) was based on self-reported history, and proliferative diabetic retinopathy (PDR) was defined as laser eye therapy; coronary artery calcium (CAC) was measured using electron-beam computed tomography. Progression of CAC (CACp) was defined as a change in the square-root-transformed CAC volume ?2.5. Predictors of each complication were examined in stepwise logistic regression with subjects with complications at baseline excluded from analyses. C-statistics, integrated discrimination indices and net-reclassification improvement were utilized for prediction performance analyses. SUA independently predicted development of incident albuminuria (OR 1.8, 95 % CI 1.2-2.7), rapid GFR decline (1.9, 1.1-3.3), DR (1.4, 1.1-1.9), PDR (2.1, 1.4-3.0) and CACp (1.5, 1.1-1.9). SUA improved the discrimination and net-classification risk of vascular complications over 6 years. SUA independently predicted the development of vascular complications in type 1 diabetes and also improved the reclassification of vascular complications.

  View details for DOI 10.1007/s00592-014-0611-1

  View details for Web of Science ID 000342427800011

  View details for PubMedID 24929955

  View details for PubMedCentralID PMC4399796

• FREQUENCY OF CONTINUOUS GLUCOSE MONITORING USE AND CHANGE IN HEMOGLOBIN A1C FOR ADULTS WITH TYPE 1 DIABETES IN A CLINICAL PRACTICE SETTING ENDOCRINE PRACTICE McQueen, R. B., Ellis, S. L., Maahs, D. M., Anderson, H. D., Nair, K. V., Campbell, J. D. 2014; 20 (10): 1007-1015

  Abstract

  To estimate the frequency of continuous glucose monitoring (CGM) use and change in hemoglobin A1c (HbA1c) compared to self-monitoring of blood glucose (SMBG) alone in adults with type 1 diabetes in a clinical practice setting.We retrospectively identified 66 adult type 1 diabetes patients at the Barbara Davis Center for Diabetes (BDC) who first initiated CGM between 2006 and 2011 and 67 controls using SMBG. The frequency of CGM use was estimated from survey recall and defined as the mean number of days/month of CGM use during a maximum follow-up of 10 months. Change in HbA1c was calculated as the difference between the baseline value and the lowest follow-up value.The mean change in HbA1c for CGM users was -0.48% (95% confidence interval [CI]: -0.67, -0.28) and for SMBG users was -0.37% (95% CI: -0.56, -0.18). The between-group mean difference in change in HbA1c, adjusted for patient characteristics, was -0.11% (95% CI: -0.38, 0.16), whereas the subgroup with a baseline HbA1c ?7.0% and users of CGM ?21 days/month was -0.36% (95% CI: -0.78, 0.05). Nearly half (n = 32, 48%) used CGM <21 days/month. The reasons for low frequency of CGM use or discontinuation included sensor costs, frequency of alarms, inaccuracy, and discomfort.These CGM data from clinical practice suggest a trend toward decreasing HbA1c for adults with type 1 diabetes, especially in patients with higher baseline HbA1c and higher frequency of CGM use. Future studies are needed to assess the use of CGM in larger populations of clinical practice adult type 1 diabetes patients.

  View details for DOI 10.4158/EP14027.OR

  View details for Web of Science ID 000350028200007

  View details for PubMedID 24793924

• Real-Time Continuous Glucose Monitoring Among Participants in the T1D Exchange Clinic Registry DIABETES CARE Wong, J. C., Foster, N. C., Maahs, D. M., Raghinaru, D., Bergenstal, R. M., Ahmann, A. J., Peters, A. L., Bode, B. W., Aleppo, G., Hirsch, I. B., Kleis, L., Chase, H. P., DuBose, S. N., Miller, K. M., Beck, R. W., Adi, S. 2014; 37 (10): 2702-2709

  Abstract

  To assess the frequency of continuous glucose monitoring (CGM) device use, factors associated with its use, and the relationship of CGM with diabetes outcomes (HbA1c, severe hypoglycemia [SH], and diabetic ketoacidosis [DKA]).Survey questions related to CGM device use 1 year after enrollment in the T1D Exchange clinic registry were completed by 17,317 participants. Participants were defined as CGM users if they indicated using real-time CGM during the prior 30 days.Nine percent of participants used CGM (6% of children <13 years old, 4% of adolescents 13 to <18 years, 6% of young adults 18 to <26 years, and 21% of adults ?26 years). CGM use was more likely with higher education, higher household income, private health insurance, longer duration of diabetes, and use of insulin pump (P < 0.01 all factors). CGM use was associated with lower HbA1c in children (8.3% vs. 8.6%, P < 0.001) and adults (7.7% vs. 7.9%, P < 0.001). In adults, more frequent use of CGM (?6 days/week) was associated with lower mean HbA1c. Only 27% of users downloaded data from their device at least once per month, and ?15% of users reported downloading their device at least weekly. Among participants who used CGM at baseline, 41% had discontinued within 1 year.CGM use is uncommon but associated with lower HbA1c in some age-groups, especially when used more frequently. Factors associated with discontinuation and infrequent use of retrospective analysis of CGM data should be considered in developing next-generation devices and education on CGM use.

  View details for DOI 10.2337/dc14-0303

  View details for PubMedID 25011947

• ISPAD Clinical Practice Consensus Guidelines 2014. Assessment and monitoring of glycemic control in children and adolescents with diabetes. Pediatric diabetes Rewers, M. J., Pillay, K., De Beaufort, C., Craig, M. E., Hanas, R., Acerini, C. L., Maahs, D. M. 2014; 15: 102-114

  View details for DOI 10.1111/pedi.12190

  View details for PubMedID 25182311

• ISPAD Clinical Practice Consensus Guidelines 2014. Type 2 diabetes in the child and adolescent. Pediatric diabetes Zeitler, P., Fu, J., Tandon, N., Nadeau, K., Urakami, T., Barrett, T., Maahs, D. 2014; 15: 26-46

  View details for DOI 10.1111/pedi.12179

  View details for PubMedID 25182306

• Assessment and management of hypoglycemia in children and adolescents with diabetes PEDIATRIC DIABETES Ly, T. T., Maahs, D. M., Rewers, A., Dunger, D., Oduwole, A., Jones, T. W. 2014; 15: 180-192

  View details for DOI 10.1111/pedi.12174

  View details for Web of Science ID 000341716900013

  View details for PubMedID 25040141

• Introduction to ISPAD Clinical Practice Consensus Guidelines 2014 Compendium PEDIATRIC DIABETES Acerini, C., Craig, M. E., De Beaufort, C., Maahs, D. M., Hanas, R. 2014; 15: 1-3

  View details for DOI 10.1111/pedi.12182

  View details for Web of Science ID 000341716900001

  View details for PubMedID 25182304

• Introduction to the limited care guidance appendix PEDIATRIC DIABETES Acerini, C. L., Craig, M. E., De Beaufort, C., Maahs, D. M., Pillay, K., Hanas, R. 2014; 15: 279-280

  View details for DOI 10.1111/pedi.12185

  View details for Web of Science ID 000341716900021

• ISPAD Clinical Practice Consensus Guidelines 2014. Assessment and management of hypoglycemia in children and adolescents with diabetes. Pediatric diabetes Ly, T. T., Maahs, D. M., Rewers, A., Dunger, D., Oduwole, A., Jones, T. W. 2014; 15: 180-192

  View details for DOI 10.1111/pedi.12174

  View details for PubMedID 25040141

• The delivery of ambulatory diabetes care to children and adolescents with diabetes PEDIATRIC DIABETES Pihoker, C., Forsander, G., Fantahun, B., Virmani, A., Luo, X., Hallman, M., Wolfsdorf, J., Maahs, D. M. 2014; 15: 86-101

  View details for DOI 10.1111/pedi.12181

  View details for Web of Science ID 000341716900008

• ISPAD Clinical Practice Consensus Guidelines 2014. The delivery of ambulatory diabetes care to children and adolescents with diabetes. Pediatric diabetes Pihoker, C., Forsander, G., Fantahun, B., Virmani, A., Luo, X., Hallman, M., Wolfsdorf, J., Maahs, D. M. 2014; 15: 86-101

  View details for DOI 10.1111/pedi.12181

  View details for PubMedID 25182310

• A practical method to measure GFR in people with type 1 diabetes JOURNAL OF DIABETES AND ITS COMPLICATIONS Maahs, D. M., Bushman, L., Kerr, B., Ellis, S. L., Pyle, L., McFann, K., Bouffard, A., Bishop, F. K., Nguyen, N., Anderson, P. L. 2014; 28 (5): 667-673

  Abstract

  Improved early diagnostic methods are needed to identify risk for kidney disease in people with type 1 diabetes. We hypothesized that glomerular filtration rate (GFR) measured by iohexol clearance in dried blood spots (DBS) on filter paper would be comparable to plasma (gold-standard) and superior to estimated GFR (eGFR) and, second, that adjustment for ambient blood glucose would improve accuracy and precision of GFR measurement.GFR was measured by iohexol clearance in plasma, DBS, and as estimated by the CKD-Epidemiology Collaboration equations in 15 adults with type 1 diabetes at two visits, one euglycemic and one hyperglycemic.GFR measured by DBS was more comparable and less biased than GFR cystatin C, serum creatinine, and both combined. GFR was higher during hyperglycemia. Correction for between visit glycemia statistically significantly reduced bias and mean squared error for GFR measured by DBS as compared to gold-standard during euglycemia.Iohexol clearance measured with DBS performed better than eGFR methods. Correction for ambient blood glucose improved precision and accuracy of GFR measurement. This method is more convenient than the gold-standard GFR method and may improve screening and diagnostic capabilities in people with type 1 diabetes, especially when GFR is >60ml/min/1.73m(2).

  View details for DOI 10.1016/j.jdiacomp.2014.06.001

  View details for Web of Science ID 000341746800017

  View details for PubMedID 25027389

• Assessment and monitoring of glycemic control in children and adolescents with diabetes PEDIATRIC DIABETES Rewers, M. J., Pillay, K., De Beaufort, C., Craig, M. E., Hanas, R., Acerini, C. L., Maahs, D. M. 2014; 15: 102-114

  View details for DOI 10.1111/pedi.12190

  View details for Web of Science ID 000341716900009

• Type 2 diabetes in the child and adolescent PEDIATRIC DIABETES Zeitler, P., Fu, J., Tandon, N., Nadeau, K., Urakami, T., Barrett, T., Maahs, D. 2014; 15: 26-46

  View details for DOI 10.1111/pedi.12179

  View details for Web of Science ID 000341716900004

• Contrasting the clinical care and outcomes of 2,622 children with type 1 diabetes less than 6 years of age in the United States T1D Exchange and German/Austrian DPV registries DIABETOLOGIA Maahs, D. M., Hermann, J. M., DuBose, S. N., Miller, K. M., Heidtmann, B., Dimeglio, L. A., Rami-Merhar, B., Beck, R. W., Schober, E., Tamborlane, W. V., Kapellen, T. M., Holl, R. W. 2014; 57 (8): 1578-1585

  Abstract

  The study aimed to compare participant characteristics, treatment modalities and clinical outcomes in registry participants less than 6 years old.Participant characteristics, treatment modalities and clinical outcomes (HbA1c, severe hypoglycaemia [SH] and diabetic ketoacidosis [DKA]) as well as frequencies of attaining HbA1c goals in line with the International Society for Pediatric and Adolescent Diabetes (<7.5% [<58 mmol/mol]) and ADA (<8.5% [<69 mmol/mol]) were compared.Insulin pump use was more frequent (74% vs 50%, p?

  View details for DOI 10.1007/s00125-014-3272-2

  View details for Web of Science ID 000338997500008

  View details for PubMedID 24893863

• Early diabetic nephropathy in type 1 diabetes: new insights CURRENT OPINION IN ENDOCRINOLOGY DIABETES AND OBESITY Bjornstad, P., Cherney, D., Maahs, D. M. 2014; 21 (4): 279-286

  Abstract

  Despite improvements in glycemic and blood pressure control in patients with type 1 diabetes, diabetic nephropathy remains the most common cause of chronic kidney disease worldwide. A major challenge in preventing diabetic nephropathy is the inability to identify high-risk patients at an early stage, emphasizing the importance of discovering new therapeutic targets and implementation of clinical trials to reduce diabetic nephropathy risk.Limitations of managing patients with diabetic nephropathy with renin-angiotensin-aldosterone system blockade have been identified in recent clinical trials, including the failure of primary prevention studies in T1D and the demonstration of harm with dual renin-angiotensin-aldosterone system blockade. Fortunately, several new targets, including serum uric acid, insulin sensitivity, vasopressin, and sodium-glucose cotransporter-2 inhibition, are promising in the prevention and treatment of diabetic nephropathy.Diabetic nephropathy is characterized by a long clinically silent period without signs or symptoms of disease. There is an urgent need for improved methods of detecting early mediators of renal injury, to ultimately prevent the initiation and progression of diabetic nephropathy. In this review, we will focus on early diabetic nephropathy and summarize potential new therapeutic targets.

  View details for DOI 10.1097/MED.0000000000000074

  View details for Web of Science ID 000338130600005

  View details for PubMedID 24983394

  View details for PubMedCentralID PMC4138314

• Multicentre prospective validation of a urinary peptidome-based classifier for the diagnosis of type 2 diabetic nephropathy NEPHROLOGY DIALYSIS TRANSPLANTATION Siwy, J., Schanstra, J. P., Argiles, A., Bakker, S. J., Beige, J., Boucek, P., Brand, K., Delles, C., Duranton, F., Fernandez-Fernandez, B., Jankowski, M., Al Khatib, M., Kunt, T., Lajer, M., Lichtinghagen, R., Lindhardt, M., Maahs, D. M., Mischak, H., Mullen, W., Navis, G., Noutsou, M., Ortiz, A., Persson, F., Petrie, J. R., Roob, J. M., Rossing, P., Ruggenenti, P., Rychlik, I., Serra, A. L., Snell-Bergeon, J., Spasovski, G., Stojceva-Taneva, O., Trillini, M., von der Leyen, H., Winklhofer-Roob, B. M., Zuerbig, P., Jankowski, J. 2014; 29 (8): 1563-1570

  Abstract

  Diabetic nephropathy (DN) is one of the major late complications of diabetes. Treatment aimed at slowing down the progression of DN is available but methods for early and definitive detection of DN progression are currently lacking. The 'Proteomic prediction and Renin angiotensin aldosterone system Inhibition prevention Of early diabetic nephRopathy In TYpe 2 diabetic patients with normoalbuminuria trial' (PRIORITY) aims to evaluate the early detection of DN in patients with type 2 diabetes (T2D) using a urinary proteome-based classifier (CKD273).In this ancillary study of the recently initiated PRIORITY trial we aimed to validate for the first time the CKD273 classifier in a multicentre (9 different institutions providing samples from 165 T2D patients) prospective setting. In addition we also investigated the influence of sample containers, age and gender on the CKD273 classifier.We observed a high consistency of the CKD273 classification scores across the different centres with areas under the curves ranging from 0.95 to 1.00. The classifier was independent of age (range tested 16-89 years) and gender. Furthermore, the use of different urine storage containers did not affect the classification scores. Analysis of the distribution of the individual peptides of the classifier over the nine different centres showed that fragments of blood-derived and extracellular matrix proteins were the most consistently found.We provide for the first time validation of this urinary proteome-based classifier in a multicentre prospective setting and show the suitability of the CKD273 classifier to be used in the PRIORITY trial.

  View details for DOI 10.1093/ndt/gfu039

  View details for Web of Science ID 000339948100019

  View details for PubMedID 24589724

  View details for PubMedCentralID PMC4118140

• A Randomized Trial of a Home System to Reduce Nocturnal Hypoglycemia in Type 1 Diabetes DIABETES CARE Maahs, D. M., Calhoun, P., Buckingham, B. A., Chase, H. P., Hramiak, I., Lum, J., Cameron, F., Bequette, B. W., Aye, T., Paul, T., Slover, R., Wadwa, R. P., Wilson, D. M., Kollman, C., Beck, R. W. 2014; 37 (7): 1885-1891

  Abstract

  Overnight hypoglycemia occurs frequently in individuals with type 1 diabetes and can result in loss of consciousness, seizure, or even death. We conducted an in-home randomized trial to determine whether nocturnal hypoglycemia could be safely reduced by temporarily suspending pump insulin delivery when hypoglycemia was predicted by an algorithm based on continuous glucose monitoring (CGM) glucose levels.Following an initial run-in phase, a 42-night trial was conducted in 45 individuals aged 15-45 years with type 1 diabetes in which each night was assigned randomly to either having the predictive low-glucose suspend system active (intervention night) or inactive (control night). The primary outcome was the proportion of nights in which ?1 CGM glucose values ?60 mg/dL occurred.Overnight hypoglycemia with at least one CGM value ?60 mg/dL occurred on 196 of 942 (21%) intervention nights versus 322 of 970 (33%) control nights (odds ratio 0.52 [95% CI 0.43-0.64]; P < 0.001). Median hypoglycemia area under the curve was reduced by 81%, and hypoglycemia lasting >2 h was reduced by 74%. Overnight sensor glucose was >180 mg/dL during 57% of control nights and 59% of intervention nights (P = 0.17), while morning blood glucose was >180 mg/dL following 21% and 27% of nights, respectively (P < 0.001), and >250 mg/dL following 6% and 6%, respectively. Morning ketosis was present <1% of the time in each arm.Use of a nocturnal low-glucose suspend system can substantially reduce overnight hypoglycemia without an increase in morning ketosis.

  View details for DOI 10.2337/dc13-2159

  View details for Web of Science ID 000338020400022

  View details for PubMedCentralID PMC4067393

• A randomized trial of a home system to reduce nocturnal hypoglycemia in type 1 diabetes. Diabetes care Maahs, D. M., Calhoun, P., Buckingham, B. A., Chase, H. P., Hramiak, I., Lum, J., Cameron, F., Bequette, B. W., Aye, T., Paul, T., Slover, R., Wadwa, R. P., Wilson, D. M., Kollman, C., Beck, R. W. 2014; 37 (7): 1885-1891

  Abstract

  Overnight hypoglycemia occurs frequently in individuals with type 1 diabetes and can result in loss of consciousness, seizure, or even death. We conducted an in-home randomized trial to determine whether nocturnal hypoglycemia could be safely reduced by temporarily suspending pump insulin delivery when hypoglycemia was predicted by an algorithm based on continuous glucose monitoring (CGM) glucose levels.Following an initial run-in phase, a 42-night trial was conducted in 45 individuals aged 15-45 years with type 1 diabetes in which each night was assigned randomly to either having the predictive low-glucose suspend system active (intervention night) or inactive (control night). The primary outcome was the proportion of nights in which ?1 CGM glucose values ?60 mg/dL occurred.Overnight hypoglycemia with at least one CGM value ?60 mg/dL occurred on 196 of 942 (21%) intervention nights versus 322 of 970 (33%) control nights (odds ratio 0.52 [95% CI 0.43-0.64]; P < 0.001). Median hypoglycemia area under the curve was reduced by 81%, and hypoglycemia lasting >2 h was reduced by 74%. Overnight sensor glucose was >180 mg/dL during 57% of control nights and 59% of intervention nights (P = 0.17), while morning blood glucose was >180 mg/dL following 21% and 27% of nights, respectively (P < 0.001), and >250 mg/dL following 6% and 6%, respectively. Morning ketosis was present <1% of the time in each arm.Use of a nocturnal low-glucose suspend system can substantially reduce overnight hypoglycemia without an increase in morning ketosis.

  View details for DOI 10.2337/dc13-2159

  View details for PubMedID 24804697

• Depression in Adults in the T1D Exchange Clinic Registry DIABETES CARE Trief, P. M., Xing, D., Foster, N. C., Maahs, D. M., Kittelsrud, J. M., Olson, B. A., Young, L. A., Peters, A. L., Bergenstal, R. M., Miller, K. M., Beck, R. W., Weinstock, R. S. 2014; 37 (6): 1563-1572

  Abstract

  Little is known about the frequency of depression in adults with type 1 diabetes (T1D) or its relationship to diabetes outcomes. The T1D Exchange clinic registry allowed us to explore depression in a large, heterogeneous sample.Participants ?18 years old (N = 6,172; median age 34 years; median diabetes duration 16 years; 55% female; and 89% non-Hispanic white) completed the eight-item Patient Health Questionnaire (PHQ-8), a validated, reliable measure of current depression. Probable major depression was defined in four ways: PHQ-8 ?10, PHQ-8 ?12, per diagnostic algorithm, and as a continuous variable. Characteristics and clinical outcomes of those with and without depression were compared using logistic and linear regression models.A total of 4.6-10.3% of participants were classified as probable major depression depending on how defined. Participants classified as depressed were more likely female, nonwhite race/ethnicity, to have a lower household income and lower education level, to exercise less often, to miss insulin doses, and to have one or more complications (neuropathy, nephropathy, treatment for retinopathy, or cardiovascular/cerebrovascular disease) (all P < 0.01). HbA1c was higher in the depressed versus not depressed groups (8.4 ± 1.7% [68 ± 8.6 mmol/mol] vs. 7.8 ± 1.4% [62 ± 15.3 mmol/mol]; P < 0.001). Occurrence of one or more diabetic ketoacidosis events (11 vs. 4%; P < 0.001) and one or more severe hypoglycemic events (18 vs. 9%; P < 0.001) in the past 3 months was higher among depressed participants.In the T1D Exchange clinic registry, adults with probable major depression have worse clinical outcomes than those not depressed. Whether identification and treatment of depression improves diabetes outcomes requires study. Depression is common in T1D, and better identification and treatment of this comorbid condition is needed.

  View details for DOI 10.2337/dc13-1867

  View details for Web of Science ID 000337746100030

  View details for PubMedID 24855157

• Association Between Glycated Hemoglobin and Health Utility for Type 1 Diabetes PATIENT-PATIENT CENTERED OUTCOMES RESEARCH McQueen, R. B., Ellis, S. L., Maahs, D. M., Anderson, H. D., Nair, K. V., Libby, A. M., Campbell, J. D. 2014; 7 (2): 197-205

  Abstract

  Cost-effectiveness models for diabetes link glycated hemoglobin (HbA1c) to diabetes-related complications. Independent of diabetes-related complications, there is little known on the association between HbA1c and health utility scores. This link can alter the cost effectiveness of interventions designed to improve HbA1c. The cross-sectional relationship between HbA1c and health utility scores in adult type 1 diabetes patients was estimated after adjusting for diabetes-related complications.The EuroQoL-5 dimension (EQ-5D) questionnaire and an ad hoc survey requesting demographic information and adherence to glucose monitoring therapies was administered to adult type 1 diabetes patients during a clinic visit and combined with clinical medical record data. Health utility scores were derived using the US time-tradeoff valuation of the EQ-5D. Linear regression was used to estimate the relationship between HbA1c and utility, adjusting for treatments, demographics, and diabetes-related complications.Among 176 patients, mean (standard deviation [SD]) age was 38 (12.2) years, duration of disease was 22 (12.1) years, and number of chronic conditions other than type 1 diabetes was 2.7 (2.0). Unadjusted mean (SD) utility was 0.94 (0.09) for those with HbA1c levels <7 % (n = 54), 0.89 (0.15) for those with HbA1c ? 7 % (n = 122), and 0.91 (0.14) for all patients. After adjustment, a 1 % absolute increase in HbA1c was associated with a disutility of -0.03 (95 % confidence interval [CI] -0.049, -0.006).Findings suggest that, after adjusting for diabetes-related complications, higher HbA1c levels are associated with a significant health disutility. Pending additional data from longitudinal studies, these findings could be used in cost-effectiveness evaluations of type 1 diabetes interventions that impact HbA1c.

  View details for DOI 10.1007/s40271-014-0045-4

  View details for Web of Science ID 000344366900008

  View details for PubMedID 24458545

• Serum uric acid and insulin sensitivity in adolescents and adults with and without type 1 diabetes JOURNAL OF DIABETES AND ITS COMPLICATIONS Bjornstad, P., Snell-Bergeon, J. K., McFann, K., Wadwa, R. P., Rewers, M., Rivard, C. J., Jalal, D., Chonchol, M. B., Johnson, R. J., Maahs, D. M. 2014; 28 (3): 298-304

  Abstract

  Decreased insulin sensitivity (IS) exists in type 1 diabetes. Serum uric acid (SUA), whose concentration is related to renal clearance, predicts vascular complications in type 1 diabetes. SUA is also inversely associated with IS in non-diabetics, but has not been examined in type 1 diabetes. We hypothesized SUA would be associated with reduced IS in adolescents and adults with type 1 diabetes.The cross-sectional and longitudinal associations of SUA with IS were investigated in 254 adolescents with type 1 diabetes and 70 without in the Determinants of Macrovascular Disease in Adolescents with Type 1 Diabetes Study, and in 471 adults with type 1 diabetes and 571 without in the Coronary Artery Calcification in Type 1 diabetes (CACTI) study.SUA was lower in subjects with type 1 diabetes (p<0.0001), but still remained inversely associated with IS after multivariable adjustments in adolescents (?±SE: -1.99±0.62, p=0.001, R2 =2%) and adults (?±SE: -0.91±0.33, p=0.006, R2 = 6%) with type 1 diabetes, though less strongly than in non-diabetic controls (adolescents: ?±SE: -2.70±1.19, p=0.03, R2 = 15%, adults: ?±SE: -5.99±0.75, p<0.0001, R2 =39%).We demonstrated a significantly weaker relationship between SUA and reduced IS in subjects with type 1 diabetes than non-diabetic controls.

  View details for DOI 10.1016/j.jdiacomp.2013.12.007

  View details for Web of Science ID 000335717800010

  View details for PubMedID 24461546

  View details for PubMedCentralID PMC4004676

• The Effects of Lowering Nighttime and Breakfast Glucose Levels with Sensor-Augmented Pump Therapy on Hemoglobin A1c Levels in Type 1 Diabetes DIABETES TECHNOLOGY & THERAPEUTICS Maahs, D. M., Chase, H. P., Westfall, E., Slover, R., Huang, S., Shin, J. J., Kaufman, F. R., Pyle, L., Snell-Bergeon, J. K. 2014; 16 (5): 284-291

  Abstract

  This study determined the association of continuous glucose monitoring glucose (CGM-glucose) levels at different times of the day with improvement in glycated hemoglobin (HbA1c) levels. The potential application of these data is to focus effort to improve glucose control in patients with type 1 diabetes.Data were analyzed from 196 patients with type 1 diabetes who were randomized to receive sensor-augmented pump therapy in the 1-year STAR 3 trial. CGM-glucose values and HbA1c levels from baseline and after 1 year were evaluated to determine associations of improvement in CGM-glucose at different times of the day with longitudinal improvement in HbA1c.Improvement in HbA1c levels after 1 year was related to improvement in mean CGM-glucose levels in daytime (6 a.m.-midnight), overnight (midnight-6 a.m.), and each mealtime period (P<0.0001 for each). In multivariable analysis, only improvement in breakfast meal period was associated with improvement in HbA1c after 1 year, explaining 59% of the HbA1c improvement using the partial R(2) test. Moreover, among those patients who only improved CGM-glucose in the overnight period there was an associated improvement in breakfast meal period CGM-glucose of 26 ± 22 mg/dL (P<0.01).Breakfast period glucose improvement had the greatest effect on lowering HbA1c levels in patients with type 1 diabetes. Improving glucose control overnight resulted in subsequent improvement in the breakfast period. Although glucose control should be improved at all times, methods to improve overnight and post-breakfast glucose levels may be of primary importance in improving glucose control in patients with type 1 diabetes.

  View details for DOI 10.1089/dia.2013.0227

  View details for Web of Science ID 000336894100003

  View details for PubMedID 24450776

• Frequency of Morning Ketosis After Overnight Insulin Suspension Using an Automated Nocturnal Predictive Low Glucose Suspend System DIABETES CARE Beck, R. W., Raghinaru, D., Wadwa, R. P., Chase, H. P., Maahs, D. M., Buckingham, B. A. 2014; 37 (5): 1224-1229

  Abstract

  To assess the effect of overnight insulin pump suspension in an automated predictive low glucose suspend system on morning blood glucose and ketone levels in an attempt to determine whether routine measurement of ketone levels is useful when a closed-loop system that suspends insulin delivery overnight is being used.Data from an in-home randomized trial of 45 individuals with type 1 diabetes (age range 15-45 years) were analyzed, evaluating an automated predictive low glucose pump suspension system in which blood glucose, blood ketone, and urine ketone levels were measured on 1,954 mornings.One or more pump suspensions occurred during 744 of the 977 intervention nights (76%). The morning blood ketone level was ?0.6 mmol/L after 11 of the 744 nights (1.5%) during which a pump suspension occurred and 2 of the 233 nights (0.9%) during which there was no suspension compared with 11 of 977 control nights (1.1%). The morning blood ketone level was ?0.6 mmol/L after only 2 of 159 nights (1.3%) with a pump suspension exceeding 2 h. Morning fasting blood glucose level was not a good predictor of the presence of blood ketones.Routine measurement of blood or urine ketones during use of an automated pump suspension system using continuous glucose monitoring, whether threshold based or predictive, is not necessary. Recommendations for checking ketone levels should be no different when a patient is using a system with automated insulin suspension than it is for conventional diabetes self-management.

  View details for DOI 10.2337/dc13-2775

  View details for Web of Science ID 000334840100034

  View details for PubMedID 24757229

  View details for PubMedCentralID PMC3994933

• Update: Ambulatory Blood Pressure Monitoring in Children and Adolescents A Scientific Statement From the American Heart Association HYPERTENSION Flynn, J. T., Daniels, S. R., Hayman, L. L., Maahs, D. M., McCrindle, B. W., Mitsnefes, M., Zachariah, J. P., Urbina, E. M. 2014; 63 (5): 1116-1135

  View details for DOI 10.1161/HYP.0000000000000007

  View details for Web of Science ID 000334320900044

  View details for PubMedID 24591341

  View details for PubMedCentralID PMC4146525

• Fasting Blood Glucose-A Missing Variable for GFR-Estimation in Type 1 Diabetes? PLOS ONE Bjornstad, P., McQueen, R. B., Snell-Bergeon, J. K., Cherney, D., Pyle, L., Perkins, B., Rewers, M., Maahs, D. M. 2014; 9 (4)

  Abstract

  Estimation of glomerular filtration rate (eGFR) is one of the current clinical methods for identifying risk for diabetic nephropathy in subjects with type 1 diabetes (T1D). Hyperglycemia is known to influence GFR in T1D and variability in blood glucose at the time of eGFR measurement could introduce bias in eGFR. We hypothesized that simultaneously measured blood glucose would influence eGFR in adults with T1D.Longitudinal multivariable mixed-models were employed to investigate the relationships between blood glucose and eGFR by CKD-EPI eGFRCYSTATIN C over 6-years in the Coronary Artery Calcification in Type 1 diabetes (CACTI) study. All subjects with T1D and complete data including blood glucose and cystatin C for at least one of the three visits (n?=?616, 554, and 521, respectively) were included in the longitudinal analyses.In mixed-models adjusting for sex, HbA1c, ACEi/ARB, protein and sodium intake positive associations were observed between simultaneous blood glucose and eGFRCYSTATIN C (?±SE:0.14±0.04 per 10 mg/dL of blood glucose, p<0.0001), and hyperfiltration as a dichotomous outcome (OR: 1.04, 95% CI: 1.01-1.07 per 10 mg/dL of blood glucose, p?=?0.02).In our longitudinal data in subjects with T1D, simultaneous blood glucose has an independent positive effect on eGFRCYSTATIN C. The associations between blood glucose and eGFRCYSTATIN C may bias the accurate detection of early diabetic nephropathy, especially in people with longitudinal variability in blood glucose.

  View details for DOI 10.1371/journal.pone.0096264

  View details for Web of Science ID 000335504900027

  View details for PubMedID 24781861

  View details for PubMedCentralID PMC4004575

• Serum Uric Acid and Hypertension in Adults: A Paradoxical Relationship in Type 1 Diabetes JOURNAL OF CLINICAL HYPERTENSION Bjornstad, P., Wadwa, R. P., Sirota, J. C., Snell-Bergeon, J. K., McFann, K., Rewers, M., Rivard, C. J., Jalal, D., Chonchol, M. B., Johnson, R. J., Maahs, D. M. 2014; 16 (4): 283-288

  Abstract

  Adults with type 1 diabetes have lower serum uric acid levels compared with nondiabetic adults. Little is known about the relationship between serum uric acid and blood pressure in type 1 diabetes and whether it differs from the positive relationship found in nondiabetic adults. The authors assessed the cross-sectional and longitudinal relationships over 6 years between serum uric acid and blood pressure in adults with (35±9 years [n=393]) and without (38±9 years [n=685]) type 1 diabetes in the Coronary Artery Calcification in Type 1 Diabetes study. In nondiabetic adults, serum uric acid was associated with systolic blood pressure in multivariable models adjusted for cardiovascular risk factors. In adults with type 1 diabetes, a negative association was observed between serum uric acid and systolic blood pressure after multivariable adjustments. A positive association was observed between serum uric acid and systolic blood pressure in nondiabetic adults. In contrast, an inverse relationship was demonstrated after multivariable adjustments in type 1 diabetes.

  View details for DOI 10.1111/jch.12305

  View details for Web of Science ID 000334290700014

  View details for PubMedID 24667019

  View details for PubMedCentralID PMC3989383

• Ideal Cardiovascular Health and the Prevalence and Progression of Coronary Artery Calcification in Adults With and Without Type 1 Diabetes DIABETES CARE Alman, A. C., Maahs, D. M., Rewers, M. J., Snell-Bergeon, J. K. 2014; 37 (2): 521-528

  Abstract

  In 2010, the American Heart Association defined seven metrics (smoking, BMI, physical activity, diet, total cholesterol, blood pressure, and fasting plasma glucose) for ideal cardiovascular health (ICH). Subsequent studies have shown that the prevalence of achieving these metrics is very low in the general population. Adults with type 1 diabetes are at increased risk of cardiovascular disease (CVD), but no studies to date have been published on the prevalence of ICH in this population.Data for this analysis were collected as part of the prospective Coronary Artery Calcification in Type 1 Diabetes study. This analysis involved 546 subjects with type 1 diabetes and 631 subjects without diabetes who had complete information for calculating the ICH metrics.Overall, the prevalence of ICH was low in this population, with none meeting the ideal criteria for all seven metrics. The prevalence of ideal physical activity (10.0%) and diet (1.1%) were particularly low. ICH was significantly associated with both decreased prevalence (odds ratio [OR] 0.70; 95% CI 0.62-0.80) and progression (OR 0.77; 95% CI 0.66-0.90) of coronary artery calcification (CAC).ICH is significantly associated with decreased prevalence and progression of CAC; however, prevalence of ICH metrics was low in adults both with and without type 1 diabetes. Efforts to increase the prevalence of ICH could have a significant impact on reducing the burden of CVD.

  View details for DOI 10.2337/dc13-0997

  View details for Web of Science ID 000331072800043

  View details for PubMedID 24130360

  View details for PubMedCentralID PMC3898750

• The effect of insurance status and parental education on glycemic control and cardiovascular disease risk profile in youth with Type 1 Diabetes. Journal of diabetes and metabolic disorders Majidi, S., Wadwa, R. P., Bishop, F. K., Klingensmith, G. J., Rewers, M., McFann, K., Maahs, D. M. 2014; 13: 59-?

  Abstract

  Adult studies have shown a correlation between low socioeconomic status and Type 1 Diabetes complications, but studies have not been done in children to examine the effect of socioeconomic status on risk for future complications. This study investigates the relationship between insurance status and parental education and both glycemic control and cardiovascular disease (CVD) risk factors in youth with type 1 diabetes.A cross-sectional study of 295 youth with established type 1 diabetes who underwent examination with fasting blood draw and reported insurance status and parental education.Youth with type 1 diabetes and public insurance had higher hemoglobin A1c (HbA1c), body mass index, hs-CRP, and blood pressure (p?

  View details for DOI 10.1186/2251-6581-13-59

  View details for PubMedID 24955334

  View details for PubMedCentralID PMC4064822

• Changes in diet and physical activity in adolescents with and without type 1 diabetes over time. International journal of pediatric endocrinology Bishop, F. K., Wadwa, R. P., Snell-Bergeon, J., Nguyen, N., Maahs, D. M. 2014; 2014 (1): 17-?

  Abstract

  Diet and physical activity (PA) are fundamental aspects of care in type 1 diabetes, but scant longitudinal data exist on these behaviors in adolescents with type 1 diabetes, especially compared to non-diabetic controls.Data in 211 adolescents with type 1 diabetes (baseline age?=?15.3?±?2.2 years, diabetes duration?=?8.8?±?3.1 years, A1c?=?9.0?±?1.5%, 51% male) and 67 non-diabetic (age?=?14.9?±?1.7 years, 52% male) controls were collected at baseline (V1) and again at 2-year follow-up (V2) (mean follow up?=?2.2?±?0.4 years). Diet data (meals/day, snacks/day, and weekly consumption of breakfast, fruit, vegetables and fried foods), and PA were collected using interviewer administered questionnaires. T-tests and chi-squared tests were used for comparisons.Both adolescents with type 1 diabetes and non-diabetic controls reported increased vegetable (2.8 v. 3.6 and 3.1 v. 3.8 times weekly, respectively, p?

  View details for DOI 10.1186/1687-9856-2014-17

  View details for PubMedID 25191342

  View details for PubMedCentralID PMC4154618

• Early Diabetic Nephropathy A complication of reduced insulin sensitivity in type 1 diabetes DIABETES CARE Bjornstad, P., Snell-Bergeon, J. K., Rewers, M., Jalal, D., Chonchol, M. B., Johnson, R. J., Maahs, D. M. 2013; 36 (11): 3678-3683

  Abstract

  Diabetic nephropathy (DN) is a major cause of mortality in type 1 diabetes. Reduced insulin sensitivity is a well-documented component of type 1 diabetes. We hypothesized that baseline insulin sensitivity would predict development of DN over 6 years.We assessed the relationship between insulin sensitivity at baseline and development of early phenotypes of DN-microalbuminuria (albumin-creatinine ratio [ACR] ?30?mg/g) and rapid renal function decline (glomerular filtration rate [GFR] loss >3 mL/min/1.73 m2 per year)-with three Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations over 6 years. Subjects with diabetes (n = 449) and without diabetes (n = 565) in the Coronary Artery Calcification in Type 1 Diabetes study had an estimated insulin sensitivity index (ISI) at baseline and 6-year follow-up.The ISI was lower in subjects with diabetes than in those without diabetes (P < 0.0001). A higher ISI at baseline predicted a lower odds of developing an ACR ?30 mg/g (odds ratio 0.65 [95% CI 0.49-0.85], P = 0.003) univariately and after adjusting for HbA1c (0.69 [0.51-0.93], P = 0.01). A higher ISI at baseline conferred protection from a rapid decline of GFR as assessed by CKD-EPI cystatin C (0.77 [0.64-0.92], P = 0.004) and remained significant after adjusting for HbA1c and age (0.80 [0.67-0.97], P = 0.02). We found no relation between ISI and rapid GFR decline estimated by CKD-EPI creatinine (P = 0.38) or CKD-EPI combined cystatin C and creatinine (P = 0.50).Over 6 years, a higher ISI independently predicts a lower odds of developing microalbuminuria and rapid GFR decline as estimated with cystatin C, suggesting a relationship between insulin sensitivity and early phenotypes of DN.

  View details for DOI 10.2337/dc13-0631

  View details for Web of Science ID 000326274100052

  View details for PubMedID 24026551

  View details for PubMedCentralID PMC3816872

• Correlates of Medical Nutrition Therapy and Cardiovascular Outcomes in Youth With Type 1 Diabetes JOURNAL OF NUTRITION EDUCATION AND BEHAVIOR The, N. S., Crandell, J. L., Thomas, J., Couch, S. C., Shah, A. S., Maahs, D. M., Dabelea, D., Marcovina, S. M., D'Agostino, R. B., Mayer-Davis, E. J. 2013; 45 (6): 661-668

  Abstract

  To examine whether the types of medical nutrition therapies (MNTs) taught to and used by youth with type 1 diabetes (T1D) vary by sociodemographic characteristics and cardiovascular (CVD) risk factors.Cross-sectional study.The SEARCH for Diabetes in Youth study is a population-based cohort of individuals with clinical diagnosed diabetes.A total of 1,191 individuals with T1D.Types of MNTs and frequency of use.Bivariate analysis and multivariate linear regression (P < .05) RESULTS: More race/ethnic minorities (vs whites), individuals with parents with less than a high school education (vs high school or higher education), and overweight/obese (vs underweight/normal weight) were taught additional MNTs. For underweight/normal weight individuals exclusively taught carbohydrate counting, those who used this approach "often" had lower hemoglobin A1c (8.6% vs 8.9%) and triglycerides (73.5 vs 84.1 mg/dL) than those who used it "sometimes/never." "Often" use of additional MNTs beyond carbohydrate counting was not associated with better mean values for CVD risk factors.In individuals with T1D, race/ethnic minorities, individuals with parents with less than a high school education, and overweight/obese individuals are taught more MNTs. Further research is needed to understand the effectiveness of the various MNTs on CVD risk factors, and to identify how to translate nutrition knowledge to behavior and metabolic status.

  View details for DOI 10.1016/j.jneb.2013.06.003

  View details for Web of Science ID 000326596800024

  View details for PubMedID 23891147

  View details for PubMedCentralID PMC3825757

• Albuminuria According to Status of Autoimmunity and Insulin Sensitivity Among Youth With Type 1 and Type 2 Diabetes DIABETES CARE Mottl, A. K., Lauer, A., Dabelea, D., Maahs, D. M., D'Agostino, R. B., Dolan, L. M., Gilliam, L. K., Lawrence, J. M., Rodriguez, B., Marcovina, S. M., Imperatore, G., Shankar, R. K., Afkarian, M., Reynolds, K., Liese, A. D., Mauer, M., Mayer-Davis, E. J. 2013; 36 (11): 3633-3638

  Abstract

  To evaluate whether etiologic diabetes type is associated with the degree of albuminuria in children with diabetes. RESEARCH DESIGN AND METHODS SEARCH: is an observational, longitudinal study of children with diabetes. Youth with newly diagnosed diabetes were classified according to diabetes autoantibody (DAA) status and presence of insulin resistance. We defined insulin resistance as an insulin sensitivity score <25th percentile for the United States general youth population. DAA status was based on positivity for the 65-kD isoform of glutamate decarboxylase and insulinoma-associated protein 2 antigens. The four etiologic diabetes type groups were as follows: DAA(+)/insulin-sensitive (IS) (n = 1,351); DAA(+)/insulin-resistant (IR) (n = 438); DAA(-)/IR (n = 379); and DAA(-)/IS (n = 233). Urinary albumin:creatinine ratio (UACR) was measured from a random urine specimen. Multivariable regression analyses assessed the independent relationship between the four diabetes type groups and magnitude of UACR.Adjusted UACR means across the four groups were as follows: DAA(+)/IS = 154 ?g/mg; DAA(+)/IR = 137 ?g/mg; DAA(-)/IR = 257 ?g/mg; and DAA(-)/IS = 131 ?g/mg (P < 0.005). Only DAA(-)/IR was significantly different. We performed post hoc multivariable regression analysis restricted to the two IR groups to explore the contribution of DAA status and insulin sensitivity (continuous) to the difference in UACR between the IR groups. Only insulin sensitivity was significantly associated with UACR (? = -0.54; P < 0.0001).In youth with diabetes, the DAA(-)/IR group had a greater UACR than all other groups, possibly because of the greater magnitude of insulin resistance. Further exploration of the relationships between severity of insulin resistance, autoimmunity, and albuminuria in youth with diabetes is warranted.

  View details for DOI 10.2337/dc13-0568

  View details for Web of Science ID 000326274100045

  View details for PubMedID 23846811

  View details for PubMedCentralID PMC3816857

• The Association between Vitamin D and Vascular Stiffness in Adolescents with and without Type 1 Diabetes PLOS ONE Lieberman, R., Wadwa, R. P., Nhung Nguyen, N., Bishop, F. K., Reinick, C., Snell-Bergeon, J. K., Maahs, D. M. 2013; 8 (10)

  View details for DOI 10.1371/journal.pone.0077272

  View details for Web of Science ID 000326270700022

• Factors Associated With Microalbuminuria in 7,549 Children and Adolescents With Type 1 Diabetes in the T1D Exchange Clinic Registry DIABETES CARE Daniels, M., DuBose, S. N., Maahs, D. M., Beck, R. W., Fox, L. A., Gubitosi-Klug, R., Laffel, L. M., Miller, K. M., Speer, H., Tamborlane, W. V., Tansey, M. J. 2013; 36 (9): 2639-2645

  Abstract

  To examine factors associated with clinical microalbuminuria (MA) diagnosis in children and adolescents in the T1D Exchange clinic registry.T1D Exchange participants <20 years of age with type 1 diabetes ? 1 year and urinary albumin-to-creatinine ratio (ACR) measured within the prior 2 years were included in the analysis. MA diagnosis required all of the following: 1) a clinical diagnosis of sustained MA or macroalbuminuria, 2) confirmation of MA diagnosis by either the most recent ACR being ? 30 mg/g or current treatment with an ACE inhibitor (ACEI) or angiotensin receptor blocker (ARB), and 3) no known cause for nephropathy other than diabetes. Logistic regression was used to assess factors associated with MA.MA was present in 329 of 7,549 (4.4%) participants, with a higher frequency associated with longer diabetes duration, higher mean glycosylated hemoglobin (HbA1c) level, older age, female sex, higher diastolic blood pressure (BP), and lower BMI (P ? 0.01 for each in multivariate analysis). Older age was most strongly associated with MA among participants with HbA1c ? 9.5% (? 80 mmol/mol). MA was uncommon (<2%) among participants with HbA1c <7.5% (<58 mmol/mol). Of those with MA, only 36% were receiving ACEI/ARB treatment.Our results emphasize the importance of good glycemic and BP control, particularly as diabetes duration increases, in order to reduce the risk of nephropathy. Since age and diabetes duration are important nonmodifiable factors associated with MA, the importance of routine screening is underscored to ensure early diagnosis and timely treatment of MA.

  View details for DOI 10.2337/dc12-2192

  View details for Web of Science ID 000323420200051

  View details for PubMedID 23610082

  View details for PubMedCentralID PMC3747908

• Impaired Renal Function Further Increases Odds of 6-Year Coronary Artery Calcification Progression in Adults With Type 1 Diabetes: The CACTI study DIABETES CARE Maahs, D. M., Jalal, D., Chonchol, M., Johnson, R. J., Rewers, M., Snell-Bergeon, J. K. 2013; 36 (9): 2607-2614

  Abstract

  To determine whether baseline estimated glomerular filtration rate (eGFR) and albumin-to-creatinine ratio (ACR) independently predict coronary artery calcification (CAC) progression, and to determine how eGFR changes over 6 years in adults with type 1 diabetes compared with nondiabetic adults.The Coronary Artery Calcification in Type 1 Diabetes study participants (n = 1,066) with complete data for eGFR assessment at baseline and 6 years were included. Three Chronic Kidney Disease Epidemiology Collaboration equations (serum creatinine, cystatin C, and both) were used to estimate eGFR. The association of baseline ACR and eGFR with CAC progression was analyzed using multiple logistic regression.Increasing categorical baseline ACR (<10, 10-30, and >30 µg/mg) predicted CAC progression in participants with type 1 diabetes (odds ratio [OR], 2.15; 95% CI, 1.50-3.09; 7.19 [3.90-13.26]; and 18.09 [8.48-38.62]), respectively, compared with nondiabetic subjects. Baseline eGFR <60 mL/min/1.73 m(2) also predicted CAC progression (OR, 5-7, compared with nondiabetic participants). ORs for CAC progression were higher in women than in men when using the cystatin C-based Chronic Kidney Disease Epidemiology Collaboration equations. Participants with type 1 diabetes had greater eGFR decreases over 6 years than nondiabetic participants using cystatin C-based equations.Although increasing ACR or decreasing eGFR predicts CAC progression, coronary atherosclerosis progresses faster in people with type 1 diabetes even in the absence of diabetic kidney disease. These findings emphasize the interaction between kidney disease and cardiovascular disease in type 1 diabetes and highlight the public health importance of lowering cardiorenal risk in people with type 1 diabetes.

  View details for DOI 10.2337/dc12-2538

  View details for Web of Science ID 000323420200047

  View details for PubMedID 23835686

  View details for PubMedCentralID PMC3747879

• Outpatient Safety Assessment of an In-Home Predictive Low-Glucose Suspend System with Type 1 Diabetes Subjects at Elevated Risk of Nocturnal Hypoglycemia DIABETES TECHNOLOGY & THERAPEUTICS Buckingham, B. A., Cameron, F., Calhoun, P., Maahs, D. M., Wilson, D. M., Chase, H. P., Bequette, B. W., Lum, J., Sibayan, J., Beck, R. W., Kollman, C. 2013; 15 (8): 622-627

  Abstract

  Abstract Objective: Nocturnal hypoglycemia is a common problem with type 1 diabetes. In the home setting, we conducted a pilot study to evaluate the safety of a system consisting of an insulin pump and continuous glucose monitor communicating wirelessly with a bedside computer running an algorithm that temporarily suspends insulin delivery when hypoglycemia is predicted. Research Design and Methods: After the run-in phase, a 21-night randomized trial was conducted in which each night was randomly assigned 2:1 to have either the predictive low-glucose suspend (PLGS) system active (intervention night) or inactive (control night). Three predictive algorithm versions were studied sequentially during the study for a total of 252 intervention and 123 control nights. The trial included 19 participants 18-56 years old with type 1 diabetes (hemoglobin A1c level of 6.0-7.7%) who were current users of the MiniMed Paradigm(®) REAL-Time Revel? System and Sof-sensor(®) glucose sensor (Medtronic Diabetes, Northridge, CA). Results: With the final algorithm, pump suspension occurred on 53% of 77 intervention nights. Mean morning glucose level was 144±48?mg/dL on the 77 intervention nights versus 133±57?mg/dL on the 37 control nights, with morning blood ketones >0.6 mmol/L following one intervention night. Overnight hypoglycemia was lower on intervention than control nights, with at least one value ?70?mg/dL occurring on 16% versus 30% of nights, respectively, with the final algorithm. Conclusions: This study demonstrated that the PLGS system in the home setting is safe and feasible. The preliminary efficacy data appear promising with the final algorithm reducing nocturnal hypoglycemia by almost 50%.

  View details for DOI 10.1089/dia.2013.0040

  View details for PubMedID 23883408

• Uric Acid Lowering to Prevent Kidney Function Loss in Diabetes: The Preventing Early Renal Function Loss (PERL) Allopurinol Study CURRENT DIABETES REPORTS Maahs, D. M., Caramori, L., Cherney, D. Z., Galecki, A. T., Gao, C., Jalal, D., Perkins, B. A., Pop-Busui, R., Rossing, P., Mauer, M., Doria, A. 2013; 13 (4): 550-559

  Abstract

  Diabetic kidney disease causes significant morbidity and mortality among people with type 1 diabetes (T1D). Intensive glucose and blood pressure control have thus far failed to adequately curb this problem and therefore a major need for novel treatment approaches exists. Multiple observations link serum uric acid levels to kidney disease development and progression in diabetes and strongly argue that uric acid lowering should be tested as one such novel intervention. A pilot of such a trial, using allopurinol, is currently being conducted by the Preventing Early Renal Function Loss (PERL) Consortium. Although the PERL trial targets T1D individuals at highest risk of kidney function decline, the use of allopurinol as a renoprotective agent may also be relevant to a larger segment of the population with diabetes. As allopurinol is inexpensive and safe, it could be cost-effective even for relatively low-risk patients, pending the completion of appropriate trials at earlier stages.

  View details for DOI 10.1007/s11892-013-0381-0

  View details for Web of Science ID 000321517000011

  View details for PubMedID 23649945

  View details for PubMedCentralID PMC3703487

• Severe Hypoglycemia and Diabetic Ketoacidosis in Adults With Type 1 Diabetes: Results From the T1D Exchange Clinic Registry JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM Weinstock, R. S., Xing, D., Maahs, D. M., Michels, A., Rickels, M. R., Peters, A. L., Bergenstal, R. M., Harris, B., DuBose, S. N., Miller, K. M., Beck, R. W. 2013; 98 (8): 3411-3419

  Abstract

  Few studies have assessed factors associated with severe hypoglycemia (SH) and diabetic ketoacidosis (DKA) in adults with type 1 diabetes (T1D).Our objective was to determine frequency of and factors associated with the occurrence of SH and DKA in adults with T1D.We conducted a cross-sectional analysis from the T1D Exchange clinic registry at 70 U.S. endocrinology centers.Analysis included 7012 participants in the T1D Exchange clinic registry aged 26 to 93 years old with T1D for ?2 years.Higher frequencies of SH and DKA were associated with lower socioeconomic status (P < .001). SH was strongly associated with diabetes duration (P < .001), with 18.6% of those with diabetes ?40 years having an event in the past 12 months. SH frequency was lowest in those with hemoglobin A1c (HbA1c) levels of 7.0% (53 mmol/mol) to 7.5% (58 mmol/mol), being higher in those with HbA1c levels <7.0% (<53 mmol/mol) or >7.5% (>58 mmol/mol). DKA frequency increased with higher HbA1c levels (P < .001), with 21.0% of those with HbA1c ?10.0% (?86 mmol/mol) having an event in the past 12 months.SH and DKA are more common in those with lower socioeconomic status. DKA, most common in those with HbA1c ?10.0% (?86 mmol/mol), should be largely preventable. In contrast, SH, most frequent with diabetes ?40 years duration, cannot be abolished given the limitation of current therapies. To reduce SH in adults with longstanding diabetes, consideration should be given to modifying HbA1c goals, particularly in patients with very low HbA1c levels.

  View details for DOI 10.1210/jc.2013-1589

  View details for Web of Science ID 000322781300060

  View details for PubMedID 23760624

• Renal Hyperfiltration and Systemic Blood Pressure in Patients with Uncomplicated Type 1 Diabetes Mellitus PLOS ONE Yang, G. K., Maahs, D. M., Perkins, B. A., Cherney, D. Z. 2013; 8 (7)

  Abstract

  Patients with type 1 diabetes mellitus (DM) and renal hyperfiltration also exhibit systemic microvascular abnormalities, including endothelial dysfunction. The effect of renal hyperfiltration on systemic blood pressure (BP) is less clear. We therefore measured BP, renal hemodynamic function and circulating renin angiotensin aldosterone system (RAAS) mediators in type 1 DM patients with hyperfiltration (n?=?36, DM-H, GFR?135 ml/min/1.73 m(2)) or normofiltration (n?=?40, DM-N), and 56 healthy controls (HC). Since renal hyperfiltration represents a state of intrarenal RAAS activation, we hypothesized that hyperfiltration would be associated with higher BP and elevated levels of circulating RAAS mediators.BP, glomerular filtration rate (GFR - inulin), effective renal plasma flow (paraaminohippurate) and circulating RAAS components were measured in DM-H, DM-N and HC during clamped euglycemia (4-6 mmol/L). Studies were repeated in DM-H and DM-N during clamped hyperglycemia (9-11 mmol/L).Baseline GFR was elevated in DM-H vs. DM-N and HC (167±6 vs. 115±2 and 115±2 ml/min/1.73 m(2), p<0.0001). Baseline systolic BP (SBP, 117±2 vs. 111±2 vs. 109±1, p?=?0.004) and heart rate (76±1 vs. 67±1 vs. 61±1, p<0.0001) were higher in DM-H vs. DM-N and HC. Despite higher SBP in DM-H, plasma aldosterone was lower in DM-H vs. DM-N and HC (42±5 vs. 86±14 vs. 276±41 ng/dl, p?=?0.01). GFR (p<0.0001) and SBP (p<0.0001) increased during hyperglycemia in DM-N but not in DM-H.DM-H was associated with higher heart rate and SBP values and an exaggerated suppression of systemic aldosterone. Future work should focus on the mechanisms that explain this paradox in diabetes of renal hyperfiltration coupled with systemic RAAS suppression.

  View details for DOI 10.1371/journal.pone.0068908

  View details for Web of Science ID 000323350700107

  View details for PubMedID 23861950

  View details for PubMedCentralID PMC3701674

• Most Youth With Type 1 Diabetes in the T1D Exchange Clinic Registry Do Not Meet American Diabetes Association or International Society for Pediatric and Adolescent Diabetes Clinical Guidelines DIABETES CARE Wood, J. R., Miller, K. M., Maahs, D. M., Beck, R. W., Dimeglio, L. A., Libman, I. M., Quinn, M., Tamborlane, W. V., Woerner, S. E. 2013; 36 (7): 2035-2037

  Abstract

  To assess the proportion of youth with type 1 diabetes under the care of pediatric endocrinologists in the United States meeting targets for HbA1c, blood pressure (BP), BMI, and lipids.Data were evaluated for 13,316 participants in the T1D Exchange clinic registry younger than 20 years old with type 1 diabetes for ?1 year.American Diabetes Association HbA1c targets of <8.5% for those younger than 6 years, <8.0% for those 6 to younger than 13 years old, and <7.5% for those 13 to younger than 20 years old were met by 64, 43, and 21% of participants, respectively. The majority met targets for BP and lipids, and two-thirds met the BMI goal of <85th percentile.Most children with type 1 diabetes have HbA1c values above target levels. Achieving American Diabetes Association goals remains a significant challenge for the majority of youth in the T1D Exchange registry.

  View details for DOI 10.2337/dc12-1959

  View details for Web of Science ID 000321472700038

  View details for PubMedID 23340893

  View details for PubMedCentralID PMC3687259

• Prospective Association Between Inflammatory Markers and Progression of Coronary Artery Calcification in Adults With and Without Type 1 Diabetes DIABETES CARE Alman, A. C., Kinney, G. L., Tracy, R. P., Maahs, D. M., Hoicanson, J. E., Rewers, M. J., Snell-Bergeon, J. K. 2013; 36 (7): 1967-1973

  Abstract

  The role of inflammation in the increased risk of cardiovascular disease in type 1 diabetes is unclear. We examined the association of inflammation and progression of coronary artery calcification (CAC)-a marker of subclinical atherosclerosis-in adults with and without type 1 diabetes.A nested case-control study was performed within the prospective cohort of the Coronary Artery Calcification in Type 1 Diabetes (CACTI) study. Participants underwent two CAC measurements ~2.5 years apart. Case subjects (n = 204) were those with significant progression of CAC. Control subjects (n = 258) were frequency-matched to case subjects on diabetes status, sex, age, and baseline CAC status. Inflammatory marker assessments were performed on stored blood samples from baseline. A principal components analysis (PCA) was performed and a composite score derived from that analysis. The composite score was constructed by assigning a value of 1 for each PCA component where at least one of the markers exceeded the 75th percentile (range 0-4). Conditional logistic regression was used for the matching strategy.The first two components of the PCA were modestly (odds ratio 1.38 [95% CI 1.08-1.77] and 1.27 [1.02-1.59], respectively) associated with CAC progression after adjustment for other risk factors. The composite score was more strongly associated with CAC progression for those with elevated markers in three or four of the principal components compared with those with none.Measures of inflammation were associated with progression of CAC in a population of adults with and without type 1 diabetes.

  View details for DOI 10.2337/dc12-1874

  View details for Web of Science ID 000321472700028

  View details for PubMedID 23340891

  View details for PubMedCentralID PMC3687315

• Physical activity, sedentary behaviors, physical fitness, and their relation to health outcomes in youth with type 1 and type 2 diabetes: A review of the epidemiologic literature JOURNAL OF SPORT AND HEALTH SCIENCE Liese, A. D., Ma, X., Maahs, D. M., Trilk, J. L. 2013; 2 (1): 21-38

  View details for DOI 10.1016/j.jshs.2012.10.005

  View details for Web of Science ID 000329871000004

• BENEFITS OF ACCELEROMETER AND HEART RATE DATA FOR HYPOGLYCEMIA MITIGATION Cameron, F., Stenerson, M., Wilson, D. M., Maahs, D. M., Mayer-Davis, E. J., Bequette, B. W., Buckingham, B. A. MARY ANN LIEBERT INC. 2013: A93?A93

  View details for Web of Science ID 000315467200257

• Estimated Insulin Sensitivity and Cardiovascular Disease Risk Factors in Adolescents with and without Type 1 Diabetes JOURNAL OF PEDIATRICS Specht, B. J., Wadwa, R. P., Snell-Bergeon, J. K., Nadeau, K. J., Bishop, F. K., Maahs, D. M. 2013; 162 (2): 297-301

  Abstract

  To test the hypothesis that cardiovascular disease (CVD) risk factors are similar in nondiabetic (non-DM) adolescents compared with those with type 1 diabetes (T1D) in the most insulin-sensitive (IS) tertile, and that CVD risk factors are more atherogenic with decreasing IS in adolescents with T1D.IS for adolescents with T1D (n = 292; age = 15.4 ± 2.1 years; duration = 8.8 ± 3.0 years, hemoglobin A1c = 8.9% ± 1.6%) and non-DM controls (n = 89; age = 15.4 ± 2.1 years) was estimated using the model: log(e)IS = .64725 - 0.02032 (waist [cm]) - 0.09779 (hemoglobin A1c [%]) - 0.00235 (triglycerides [mg/dL]). CVD risk factors (blood pressure, fasting total and low- and high-density lipoprotein-cholesterol (HDL-c), high sensitivity C-reactive protein, and body mass index z score) were compared between all non-DM adolescents and those with T1D in the most IS tertile, and then examined for a linear trend by IS tertile in adolescents with T1D, adjusted for sex, race/ethnicity, and Tanner stage.Estimated IS was significantly lower in adolescents with T1D compared with those without (T1D = 7.8 ± 2.4, non-DM = 11.5 ± 2.9; P < .0001). CVD risk factors were similar for non-DM compared with the adolescents with T1D with the most IS, except for higher (HDL-c) and diastolic blood pressure in adolescents with T1D (P < .05). Among adolescents with T1D, all CVD risk factors except for (HDL-c), were more atherogenic across decreasing IS tertiles in linear regression analysis (P < .05).Adolescents with T1D who are the most IS have similar CVD risk factors compared with non-DM adolescents. CVD risk factors are inversely associated with IS in adolescents with T1D. IS may be an important therapeutic target for reducing CVD risk factors in adolescents with T1D.

  View details for DOI 10.1016/j.jpeds.2012.07.036

  View details for Web of Science ID 000313579900017

  View details for PubMedID 22921593

  View details for PubMedCentralID PMC3509245

• USING ACTIVITY MONITORS TO IMPROVE CGM SENSOR ANOMALY DETECTION BAYSAL, N., Cameron, F., Stenerson, M., Buckingham, B. A., Wilson, D. M., Mayer-Davis, E. J., Maahs, D. M., Bequette, B. W. MARY ANN LIEBERT INC. 2013: A2?A2

  View details for Web of Science ID 000315467200005

• Lower A1c among adolescents with lower perceived A1c goal: a cross-sectional survey. International journal of pediatric endocrinology Clements, S. A., Anger, M. D., Bishop, F. K., McFann, K. K., Klingensmith, G. J., Maahs, D. M., Wadwa, R. P. 2013; 2013 (1): 17-?

  Abstract

  The International Society for Pediatric and Adolescent Diabetes (ISPAD) and the American Diabetes Association (ADA) have established a hemoglobin A1c (A1c) target of less than 7.5% for adolescents with type 1 diabetes (T1D). However, many adolescents are unaware of their A1c target, and little data exist on how knowledge of this A1c target affects the actual A1c they achieve. We sought to evaluate the relationship between awareness of the A1c target and the actual A1c achieved in adolescents with T1D.In a cohort of 240 adolescents with T1D age 13-19 years, we measured A1c and administered a questionnaire to assess their knowledge of the ISPAD guideline for A1c target.Of the total cohort, 42 subjects (18%) had an A1c below target and 198 subjects (82%) had an A1c above target. Almost all subjects (98%) reported that they were told their A1c target by a healthcare provider, and most of those (88%) claimed to know their A1c target, but few (8%) were correct. More subjects with actual A1c below 7.5% thought their A1c goal was lower than the ISPAD target, compared to subjects with A1c above target (75% vs. 59%, p?=?0.07), although this did not achieve statistical significance.In this cohort of adolescents with T1D, there was a trend toward a lower achieved A1c in those with a lower perceived A1c goal. Further studies should focus on identification of factors influencing an adolescent's ability to achieve a lower A1c.

  View details for DOI 10.1186/1687-9856-2013-17

  View details for PubMedID 24156395

  View details for PubMedCentralID PMC4015741

• The Importance of Palmitoleic Acid to Adipocyte Insulin Resistance and Whole-Body Insulin Sensitivity in Type 1 Diabetes JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM Bergman, B. C., Howard, D., Schauer, I. E., Maahs, D. M., Snell-Bergeon, J. K., Clement, T. W., Eckel, R. H., Perreault, L., Rewers, M. 2013; 98 (1): E40-E50

  Abstract

  Type 1 diabetes is an insulin-resistant state, but it is less clear which tissues are affected. Our previous report implicated skeletal muscle and liver insulin resistance in people with type 1 diabetes, but this occurred independently of generalized, visceral, or ectopic fat.The aim of the study was to measure adipose tissue insulin sensitivity and plasma triglyceride composition in individuals with type 1 diabetes after overnight insulin infusion to lower fasting glucose.Fifty subjects (25 individuals with type 1 diabetes and 25 controls without) were studied. After 3 d of dietary control and overnight insulin infusion, we performed a three-stage hyperinsulinemic/euglycemic clamp infusing insulin at 4, 8, and 40 mU/m(2) · min. Infusions of [1,1,2,3,3-(2)H(2)]glycerol and [1-(13)C]palmitate were used to quantify lipid metabolism.Basal glycerol and palmitate rates of appearance were similar between groups, decreased more in control subjects during the first two stages of the clamp, and similarly suppressed during the highest insulin dose. The concentration of insulin required for 50% inhibition of lipolysis was twice as high in individuals with type 1 diabetes. Plasma triglyceride saturation was similar between groups, but palmitoleic acid in plasma triglyceride was inversely related to adipocyte insulin sensitivity. Unesterified palmitoleic acid in plasma was positively related to insulin sensitivity in controls, but not in individuals with type 1 diabetes.Adipose tissue insulin resistance is a significant feature of type 1 diabetes. Palmitoleic acid is not related to insulin sensitivity in type 1 diabetes, as it was in controls, suggesting a novel mechanism for insulin resistance in this population.

  View details for DOI 10.1210/jc.2012-2892

  View details for Web of Science ID 000316210300006

  View details for PubMedID 23150678

  View details for PubMedCentralID PMC3537110

• Glucose Control Predicts 2-Year Change in Lipid Profile in Youth with Type 1 Diabetes JOURNAL OF PEDIATRICS Maahs, D. M., Dabelea, D., D'Agostino, R. B., Andrews, J. S., Shah, A. S., Crimmins, N., Mayer-Davis, E. J., Marcovina, S., Imperatore, G., Wadwa, R. P., Daniels, S. R., Reynolds, K., Hamman, R. F., Dolan, L. M. 2013; 162 (1): 101-U127

  Abstract

  To test the hypothesis that a change in glycated hemoglobin (A1c) over a follow-up interval of approximately 2 years would be associated with concomitant changes in fasting lipids in individuals with type 1 diabetes (T1D).All subjects with T1D diagnosed in 2002-2005 in the SEARCH for Diabetes in Youth study with at least 2 study visits ?12 and ?24 months after an initial visit were included (age at initial visit, 10.6 ± 4.1 years; 48% female; diabetes duration, 10 ± 7 months; 76% non-Hispanic white; A1c = 7.7% ± 1.4%). Longitudinal mixed models were fit to examine the relationship between change in A1c and change in lipid levels (total cholesterol [TC], high-density lipoprotein-cholesterol [HDL-c], low-density lipoprotein-cholesterol [LDL-c], log triglycerides [TG], and non-HDL-c) with adjustment for possible confounders.Change in A1c over time was significantly associated with changes in TC, HDL-c, LDL-c, TG, and non-HDL-c over the range of A1c values. For example, for a person with an A1c of 10% and then a 2% decrease in A1c 2 years later (to 8%), the model predicted concomitant changes in TC (-0.29 mmol/L, -11.4 mg/dL), HDL-c (0.03 mmol/L, 1.3 mg/dL), LDL-c (-0.23 mmol/L, -9.0 mg/dL), and non-HDL-c (-0.32 mmol/L, -12.4 mg/dL) and an 8.5% decrease in TG (mmol/L).Improved glucose control over a 2-year follow-up was associated with a more favorable lipid profile but may be insufficient to normalize lipids in dyslipidemic T1D youth needing to decrease lipids to goal.

  View details for DOI 10.1016/j.jpeds.2012.06.006

  View details for Web of Science ID 000312915900024

  View details for PubMedID 22795314

  View details for PubMedCentralID PMC3807690

• The association between vitamin D and vascular stiffness in adolescents with and without type 1 diabetes. PloS one Lieberman, R., Wadwa, R. P., Nguyen, N., Bishop, F. K., Reinick, C., Snell-Bergeon, J. K., Maahs, D. M. 2013; 8 (10)

  Abstract

  Vitamin D deficiency is common and associated with increased cardiovascular disease (CVD) risk. Pulse wave velocity (PWV) is a marker of vascular stiffness associated with CVD. We hypothesized that Vitamin D (25 (OH) D) levels would be inversely associated with PWV in youth with and without type 1 diabetes (T1D).Comparisons were made between adolescents with T1D (n = 211; age = 17.5 ± 2.3 years; diabetes duration = 10.9 ± 3.2 years; A1c = 9.1 ± 1.7%) and non-DM controls (n = 67; age = 16.9 ± 1.9 years). PWV was measured in the carotid-femoral segment (Sphygmocor Vx, AtCor Medical, Lisle, IL).Vitamin D levels were similar in adolescents with T1D and controls (27.7 ± 0.7 v. 26.0 ± 1.3 ng/ml; p = 0.26). Vitamin D was significantly inversely associated with PWV after adjusting for age, sex, quarter of the year, and race-ethnicity in adolescents with T1D (beta = -0.01 ± 0.004, p = 0.02) but not in the non-DM adolescents (beta = -0.008 ± 0.008, p = 0.32). Vitamin D remained significantly associated with PWV after additionally adjusting for hs-CRP in adolescents with T1D (-0.01 ± 0.004, p = 0.01). After adjusting for BMI z-score, lipids, or blood pressure, the relationship of Vitamin D with PWV was not significant.Vitamin D levels were inversely associated with PWV in adolescents with T1D, but not independently of BMI, lipids, or blood pressure. Our data contrast with other reports and suggest further research is indicated to determine if Vitamin D supplementation would be beneficial to lower CVD risk in adolescents with T1D with vitamin D insufficiency or deficiency.

  View details for DOI 10.1371/journal.pone.0077272

  View details for PubMedID 24204786

  View details for PubMedCentralID PMC3812200

• Randomized Nutrition Education Intervention to Improve Carbohydrate Counting in Adolescents with Type 1 Diabetes Study: Is More Intensive Education Needed? JOURNAL OF THE ACADEMY OF NUTRITION AND DIETETICS Spiegel, G., Bortsov, A., Bishop, F. K., Owen, D., Klingensmith, G. J., Mayer-Davis, E. J., Maahs, D. M. 2012; 112 (11): 1736-1746

  Abstract

  Youth with type 1 diabetes do not count carbohydrates accurately, yet it is an important strategy in blood glucose control.The study objective was to determine whether a nutrition education intervention would improve carbohydrate counting accuracy and glycemic control.We conducted a randomized, controlled nutrition intervention trial that was recruited from February 2009 to February 2010.Youth (12 to 18 years of age, n = 101) with type 1 diabetes were screened to identify those with poor carbohydrate counting accuracy, using a previously developed carbohydrate counting accuracy test covering commonly consumed foods and beverage items presented in six mixed meals and two snacks. All participants (n = 66, age = 15 ± 3 years, 41 male, diabetes duration = 6 ± 4 years, hemoglobin A1c [HbA1c] = 8.3% ± 1.1%) were randomized to the control or intervention group at the baseline visit. The intervention group attended a 90-minute class with a registered dietitian/certified diabetes educator and twice kept 3-day food records, which were used to review carbohydrate counting progress.Carbohydrate counting accuracy (measured as described) and HbA1c were evaluated at baseline and 3 months to determine the effectiveness of the intervention.t Tests, Spearman correlations, and repeated measures models were used.At baseline, carbohydrate content was over- and underestimated in 16 and 5 of 29 food items, respectively. When foods were presented as mixed meals, participants either significantly over- or underestimated 10 of the 9 meals and 4 snacks. After 3 months of follow-up, HbA1c decreased in both the intervention and control groups by -0.19% ± 0.12% (P = 0.12) and -0.08% ± 0.11% (P = 0.51), respectively; however, the overall intervention effect was not statistically significant for change in HbA1c or carbohydrate counting accuracy.More intensive intervention might be required to improve adolescents' carbohydrate counting accuracy and nutrition management of type 1 diabetes. Additional research is needed to translate nutrition education into improved health outcomes.

  View details for DOI 10.1016/j.jand.2012.06.001

  View details for Web of Science ID 000310819200006

  View details for PubMedID 22975086

  View details for PubMedCentralID PMC3487717

• Implementation of proteomic biomarkers: making it work EUROPEAN JOURNAL OF CLINICAL INVESTIGATION Mischak, H., Ioannidis, J. P., Argiles, A., Attwood, T. K., Bongcam-Rudloff, E., Broenstrup, M., Charonis, A., Chrousos, G. P., Delles, C., Dominiczak, A., Dylag, T., Ehrich, J., Egido, J., Findeisen, P., Jankowski, J., Johnson, R. W., Julien, B. A., Lankisch, T., Leung, H. Y., Maahs, D., Magni, F., Manns, M. P., Manolis, E., Mayer, G., Navis, G., Novak, J., Ortiz, A., Persson, F., Peter, K., Riese, H. H., Rossing, P., Sattar, N., Spasovski, G., Thongboonkerd, V., Vanholder, R., Schanstra, J. P., Vlahou, A. 2012; 42 (9): 1027-1036

  Abstract

  While large numbers of proteomic biomarkers have been described, they are generally not implemented in medical practice. We have investigated the reasons for this shortcoming, focusing on hurdles downstream of biomarker verification, and describe major obstacles and possible solutions to ease valid biomarker implementation. Some of the problems lie in suboptimal biomarker discovery and validation, especially lack of validated platforms with well-described performance characteristics to support biomarker qualification. These issues have been acknowledged and are being addressed, raising the hope that valid biomarkers may start accumulating in the foreseeable future. However, successful biomarker discovery and qualification alone does not suffice for successful implementation. Additional challenges include, among others, limited access to appropriate specimens and insufficient funding, the need to validate new biomarker utility in interventional trials, and large communication gaps between the parties involved in implementation. To address this problem, we propose an implementation roadmap. The implementation effort needs to involve a wide variety of stakeholders (clinicians, statisticians, health economists, and representatives of patient groups, health insurance, pharmaceutical companies, biobanks, and regulatory agencies). Knowledgeable panels with adequate representation of all these stakeholders may facilitate biomarker evaluation and guide implementation for the specific context of use. This approach may avoid unwarranted delays or failure to implement potentially useful biomarkers, and may expedite meaningful contributions of the biomarker community to healthcare.

  View details for DOI 10.1111/j.1365-2362.2012.02674.x

  View details for Web of Science ID 000307473300014

  View details for PubMedID 22519700

  View details for PubMedCentralID PMC3464367

• Inpatient studies of a Kalman-filter-based predictive pump shutoff algorithm. Journal of diabetes science and technology Cameron, F., Wilson, D. M., Buckingham, B. A., Arzumanyan, H., Clinton, P., Chase, H. P., Lum, J., Maahs, D. M., Calhoun, P. M., Bequette, B. W. 2012; 6 (5): 1142-1147

  Abstract

  An insulin pump shutoff system can prevent nocturnal hypoglycemia and is a first step on the pathway toward a closed-loop artificial pancreas. In previous pump shutoff studies using a voting algorithm and a 1 min continuous glucose monitor (CGM), 80% of induced hypoglycemic events were prevented.The pump shutoff algorithm used in previous studies was revised to a single Kalman filter to reduce complexity, incorporate CGMs with different sample times, handle sensor signal dropouts, and enforce safety constraints on the allowable pump shutoff time.Retrospective testing of the new algorithm on previous clinical data sets indicated that, for the four cases where the previous algorithm failed (minimum reference glucose less than 60 mg/dl), the mean suspension start time was 30 min earlier than the previous algorithm. Inpatient studies of the new algorithm have been conducted on 16 subjects. The algorithm prevented hypoglycemia in 73% of subjects. Suspension-induced hyperglycemia is not assessed, because this study forced excessive basal insulin infusion rates.The new algorithm functioned well and is flexible enough to handle variable sensor sample times and sensor dropouts. It also provides a framework for handling sensor signal attenuations, which can be challenging, particularly when they occur overnight.

  View details for PubMedID 23063041

  View details for PubMedCentralID PMC3570849

• Outpatient Assessment of Determinants of Glucose Excursions in Adolescents with Type 1 Diabetes: Proof of Concept DIABETES TECHNOLOGY & THERAPEUTICS Maahs, D. M., Mayer-Davis, E., Bishop, F. K., Wang, L., Mangan, M., McMurray, R. G. 2012; 14 (8): 658-664

  Abstract

  Abstract Objective: Controlled inpatient studies on the effects of food, physical activity (PA), and insulin dosing on glucose excursions exist, but such outpatient data are limited. We report here outpatient data on glucose excursions and its key determinants over 5 days in 30 adolescents with type 1 diabetes (T1D) as a proof-of-principle pilot study.Subjects (20 on insulin pumps, 10 receiving multiple daily injections; 15±2 years old; diabetes duration, 8±4 years; hemoglobin A1c, 8.1±1.0%) wore a continuous glucose monitor (CGM) and an accelerometer for 5 days. Subjects continued their existing insulin regimens, and time-stamped insulin dosing data were obtained from insulin pump downloads or insulin pen digital logs. Time-stamped cell phone photographs of food pre- and post-consumption and food logs were used to augment 24-h dietary recalls for Days 1 and 3. These variables were incorporated into regression models to predict glucose excursions at 1-4?h post-breakfast.CGM data on both Days 1 and 3 were obtained in 57 of the possible 60 subject-days with an average of 125 daily CGM readings (out of a possible 144). PA and dietary recall data were obtained in 100% and 93% of subjects on Day 1 and 90% and 100% of subjects on Day 3, respectively. All of these variables influenced glucose excursions at 1-4?h after waking, and 56 of the 60 subject-days contributed to the modeling analysis.Outpatient high-resolution time-stamped data on the main inputs of glucose variability in adolescents with T1D are feasible and can be modeled. Future applications include using these data for in silico modeling and for monitoring outpatient iterations of closed-loop studies, as well as to improve clinical advice regarding insulin dosing to match diet and PA behaviors.

  View details for DOI 10.1089/dia.2012.0053

  View details for Web of Science ID 000307125800004

  View details for PubMedID 22853720

  View details for PubMedCentralID PMC3409451

• Early Detection of Kidney Disease in Type 1 Diabetes: What Do We Really Know? DIABETES TECHNOLOGY & THERAPEUTICS Maahs, D. M. 2012; 14 (7): 541-544

  View details for DOI 10.1089/dia.2012.0089

  View details for Web of Science ID 000306245600001

  View details for PubMedID 22540522

• Cardiovascular Disease in Children and Adolescents with Diabetes: Where Are We, and Where Are We Going? DIABETES TECHNOLOGY & THERAPEUTICS Truong, U. T., Maahs, D. M., Daniels, S. R. 2012; 14: S11-S21

  Abstract

  The increasing prevalence of type 1 and type 2 diabetes mellitus combined with advancement in early detection of cardiovascular disease (CVD) has placed CVD as a significant concern for preventative pediatric medicine. The public health burden of type 2 diabetes is predicted to parallel increasing obesity in children with a projected increase of early CVD in adulthood. In this article, we review practice guidelines for cardiovascular health in children and adolescents with diabetes and data on which they are based. We then focus on imaging modalities that are promising tools to expand our understanding of the cardiovascular risk imposed on youths with diabetes.

  View details for DOI 10.1089/dia.2012.0018

  View details for Web of Science ID 000304752300003

  View details for PubMedID 22650220

  View details for PubMedCentralID PMC4239674

• Current Knowledge and Future Directions on Cardiovascular Disease in Diabetes DIABETES TECHNOLOGY & THERAPEUTICS Maahs, D. M., Snell-Bergeon, J. K. 2012; 14: S75-S76

  View details for DOI 10.1089/dia.2012.0106

  View details for Web of Science ID 000304752300010

  View details for PubMedID 22650228

  View details for PubMedCentralID PMC4971415

• Cardiovascular Disease (CVD) Limbo: How Soon and Low Should We Go to Prevent CVD in Diabetes? DIABETES TECHNOLOGY & THERAPEUTICS Maahs, D. M. 2012; 14 (6): 449-452

  View details for DOI 10.1089/dia.2012.0078

  View details for Web of Science ID 000304788400001

  View details for PubMedID 22472062

• Features of Hepatic and Skeletal Muscle Insulin Resistance Unique to Type 1 Diabetes JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM Bergman, B. C., Howard, D., Schauer, I. E., Maahs, D. M., Snell-Bergeon, J. K., Eckel, R. H., Perreault, L., Rewers, M. 2012; 97 (5): 1663-1672

  Abstract

  Type 1 diabetes is known to be a state of insulin resistance; however, the tissues involved in whole-body insulin resistance are less well known. It is unclear whether insulin resistance is due to glucose toxicity in the post-Diabetes Control and Complications Trial era of tighter glucose control.We performed this study to determine muscle and liver insulin sensitivity individuals with type 1 diabetes after overnight insulin infusion to lower fasting glucose concentration.Fifty subjects [25 controls without and 25 individuals with type 1 diabetes (diabetes duration 22.9 ± 1.7 yr, without known end organ damage] were frequency matched on age and body mass index by group and studied. After 3 d of dietary control and overnight insulin infusion to normalize glucose, we performed a three-stage hyperinsulinemic/euglycemic clamp infusing insulin at 4, 8, and 40 mU/m(2) · min. Glucose metabolism was quantified using an infusion of [6,6-(2)H(2)]glucose. Hepatic insulin sensitivity was measured using the insulin IC(50) for glucose rate of appearance (Ra), whereas muscle insulin sensitivity was measured using the glucose rate of disappearance during the highest insulin dose.Throughout the study, glucose Ra was significantly greater in individuals compared with those without type 1 diabetes. The concentration of insulin required for 50% suppression of glucose Ra was 2-fold higher in subjects with type 1 diabetes. Glucose rate of disappearance was significantly lower in individuals with type 1 diabetes during the 8- and 40-mU/m(2) · min stages.Insulin resistance in liver and skeletal muscle was a significant feature in type 1 diabetes. Nevertheless, the etiology of insulin resistance was not explained by body mass index, percentage fat, plasma lipids, visceral fat, and physical activity and was also not fully explained by hyperglycemia.

  View details for DOI 10.1210/jc.2011-3172

  View details for Web of Science ID 000303915900059

  View details for PubMedID 22362823

  View details for PubMedCentralID PMC3339891

• Adiponectin Dysregulation and Insulin Resistance in Type 1 Diabetes JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM Pereira, R. I., Snell-Bergeon, J. K., Erickson, C., Schauer, I. E., Bergman, B. C., Rewers, M., Maahs, D. M. 2012; 97 (4): E642-E647

  Abstract

  Type 1 diabetes (T1D) is associated with insulin resistance despite elevated levels of the insulin-sensitizing protein adiponectin. Whether the expected positive correlation between adiponectin and insulin sensitivity is preserved in a T1D population is unknown.We measured the correlation between total and high-molecular-weight (HMW) adiponectin and insulin sensitivity in T1D patients and nondiabetic controls and identified determinants of adiponectin levels in patients with T1D.Fasting total and HMW adiponectin were measured in 86 subjects from the Coronary Artery Calcification in T1D (CACTI) cohort (39 T1D, 47 nondiabetic; age 45 ± 8 yr; 55% female). The association of adiponectin levels with insulin sensitivity was analyzed.The study was conducted at an academic research institute.Fasting total and HMW adiponectin were measured by RIA and ELISA, respectively. Insulin sensitivity was measured by a hyperinsulinemic-euglycemic clamp. Multivariate linear regression was used to identify determinants of adiponectin levels.Adiponectin levels positively correlated with insulin sensitivity in both subject groups (total adiponectin, r = 0.33 P < 0.05 for T1D, r = 0.29 P < 0.05 controls), but insulin sensitivity was lower in T1D subjects at any given level of total or HMW adiponectin. Adiponectin levels were independently associated with age, gender, and trunk fat, but these variables did not account for increased adiponectin in patients with T1D.Adiponectin levels are positively correlated with insulin sensitivity in T1D patients. However, T1D patients have decreased insulin sensitivity compared with controls at every level of adiponectin, suggesting an important adaptive change of adiponectin set point.

  View details for DOI 10.1210/jc.2011-2542

  View details for Web of Science ID 000302787800019

  View details for PubMedID 22278421

  View details for PubMedCentralID PMC3319187

• Novel Urinary Protein Biomarkers Predicting the Development of Microalbuminuria and Renal Function Decline in Type 1 Diabetes DIABETES CARE Schlatzer, D., Maahs, D. M., Chance, M. R., Dazard, J., Li, X., Hazlett, F., Rewers, M., Snell-Bergeon, J. K. 2012; 35 (3): 549-555

  Abstract

  To define a panel of novel protein biomarkers of renal disease.Adults with type 1 diabetes in the Coronary Artery Calcification in Type 1 Diabetes study who were initially free of renal complications (n = 465) were followed for development of micro- or macroalbuminuria (MA) and early renal function decline (ERFD, annual decline in estimated glomerular filtration rate of ?3.3%). The label-free proteomic discovery phase was conducted in 13 patients who progressed to MA by the 6-year visit and 11 control subjects, and four proteins (Tamm-Horsfall glycoprotein, ?-1 acid glycoprotein, clusterin, and progranulin) identified in the discovery phase were measured by enzyme-linked immunosorbent assay in 74 subjects: group A, normal renal function (n = 35); group B, ERFD without MA (n = 15); group C, MA without ERFD (n = 16); and group D, both ERFD and MA (n = 8).In the label-free analysis, a model of progression to MA was built using 252 peptides, yielding an area under the curve (AUC) of 84.7 ± 5.3%. In the validation study, ordinal logistic regression was used to predict development of ERFD, MA, or both. A panel including Tamm-Horsfall glycoprotein (odds ratio 2.9, 95% CI 1.3-6.2, P = 0.008), progranulin (1.9, 0.8-4.5, P = 0.16), clusterin (0.6, 0.3-1.1, P = 0.09), and ?-1 acid glycoprotein (1.6, 0.7-3.7, P = 0.27) improved the AUC from 0.841 to 0.889.A panel of four novel protein biomarkers predicted early renal damage in type 1 diabetes. These findings require further validation in other populations for prediction of renal complications and treatment monitoring.

  View details for DOI 10.2337/dc11-1491

  View details for Web of Science ID 000300801400020

  View details for PubMedID 22238279

  View details for PubMedCentralID PMC3322681

• Update on care of children with type 1 diabetes. Advances in pediatrics Majidi, S., Maahs, D. M. 2012; 59 (1): 303-327

  View details for DOI 10.1016/j.yapd.2012.04.007

  View details for PubMedID 22789584

• Is Carbohydrate Counting Enough? Towards Perfection or Unwanted Complexity? DIABETES TECHNOLOGY & THERAPEUTICS Maahs, D. M., Higgins, J. 2012; 14 (1): 3-5

  View details for DOI 10.1089/dia.2011.0234

  View details for Web of Science ID 000298816300002

  View details for PubMedID 22066526

• Lessons learned from a lipid lowering trial in adolescents with type 1 diabetes. International journal of pediatric endocrinology Bishop, F. K., Wadwa, R. P., Ellis, S., Rewers, M., Maahs, D. M. 2012; 2012 (1): 24-?

  Abstract

  Herein, we describe recruitment efforts for a trial of lipid-lowering medications in adolescents with type 1 diabetes, age 12-21?years. Based on our experience, future studies will require multiple centers to enroll a sufficient number of participants for adequate data to direct dyslipidemia medication treatment guidelines for adolescents with type 1 diabetes.

  View details for DOI 10.1186/1687-9856-2012-24

  View details for PubMedID 22846167

  View details for PubMedCentralID PMC3476991

• Sugar-sweetened and diet beverage consumption is associated with cardiovascular risk factor profile in youth with type 1 diabetes ACTA DIABETOLOGICA Bortsov, A. V., Liese, A. D., Bell, R. A., Dabelea, D., D'Agostino, R. B., Hamman, R. F., Klingensmith, G. J., Lawrence, J. M., Maahs, D. M., McKeown, R., Marcovina, S. M., Thomas, J., Williams, D. E., Mayer-Davis, E. J. 2011; 48 (4): 275-282

  Abstract

  The prevalence of cardiovascular disease (CVD) risk factors among youth with type 1 diabetes is high and associated with age, gender, and race/ethnicity. It has also been shown that youth with type 1 diabetes often do not follow dietary recommendations. The objective of this cross-sectional observational study was to explore the association of sugar-sweetened and diet beverage intake with A1c, plasma lipids, adiponectin, leptin, systolic, and diastolic blood pressure in youth with type 1 diabetes. We examined data from 1,806 youth age 10-22 years with type 1 diabetes, of which 22% were minority (10% Hispanic, 8% African Americans, 4% other races) and 48% were female. Sugar-sweetened beverage, diet beverage, and mineral water intake was assessed with a food frequency questionnaire. After adjustment for socio-demographic and clinical covariates, physical activity and total energy intake, high sugar-sweetened beverage intake (at least one serving per day vs. none), was associated with higher levels of total cholesterol, LDL cholesterol, and plasma triglycerides, but not with A1c. High diet beverage intake was associated with higher A1c, total cholesterol, LDL cholesterol, and triglycerides. These associations were partially confounded by body mass index, saturated fat and total fiber intake. High sugar-sweetened beverage intake may have an adverse effect on CVD risk in youth with type 1 diabetes. Diet beverage intake may be a marker of unhealthy lifestyle which, in turn, is associated with worse metabolic control and CVD risk profile in these youth. Youth with diabetes should be encouraged to minimize sugar-sweetened beverage intake.

  View details for DOI 10.1007/s00592-010-0246-9

  View details for Web of Science ID 000297515600002

  View details for PubMedID 21249401

  View details for PubMedCentralID PMC4669040

• Age and Sex Influence Cystatin C in Adolescents With and Without Type 1 Diabetes DIABETES CARE Maahs, D. M., Prentice, N., McFann, K., Snell-Bergeon, J. K., Jalal, D., Bishop, F. K., Aragon, B., Wadwa, R. P. 2011; 34 (11): 2360-2362

  Abstract

  To compare serum cystatin C levels, a novel biomarker of renal function, in adolescents with and without type 1 diabetes and to determine what factors affect cystatin C levels.Cystatin C was measured in youth 12-19 years of age with (n = 259, diabetes duration 9 ± 3 years, HbA(1c) 8.9 ± 1.6%) and without diabetes (n = 78). Data were compared by diabetes status, and linear regression was used to determine factors affecting cystatin C.Cystatin C (0.698 ± 0.083 vs. 0.688 ± 0.127 mg/L, P = 0.40) was similar by diabetes status. In multiple linear regression, cystatin C was associated with age and serum creatinine in nondiabetic subjects and sex, age, and serum creatinine in subjects with diabetes (P < 0.05).These data suggest sex differences and age-related changes in cystatin C in adolescents with type 1 diabetes. An understanding of these changes is needed to determine the potential role of cystatin C as a marker of renal function in this population.

  View details for DOI 10.2337/dc11-0829

  View details for Web of Science ID 000296955100005

  View details for PubMedID 21926294

  View details for PubMedCentralID PMC3198267

• Childhood obesity and cardiovascular disease: links and prevention strategies NATURE REVIEWS CARDIOLOGY Nadeau, K. J., Maahs, D. M., Daniels, S. R., Eckel, R. H. 2011; 8 (9): 513-525

  Abstract

  The prevalence and severity of pediatric obesity have dramatically increased since the late 1980s, raising concerns about a subsequent increase in cardiovascular outcomes. Strong evidence, particularly from autopsy studies, supports the concept that precursors of adult cardiovascular disease (CVD) begin in childhood, and that pediatric obesity has an important influence on overall CVD risk. Lifestyle patterns also begin early and impact CVD risk. In addition, obesity and other CVD risk factors tend to persist over time. However, whether childhood obesity causes adult CVD directly, or does so by persisting as adult obesity, or both, is less clear. Regardless, sufficient data exist to warrant early implementation of both obesity prevention and treatment in youth and adults. In this Review, we examine the evidence supporting the impact of childhood obesity on adult obesity, surrogate markers of CVD, components of the metabolic syndrome, and the development of CVD. We also evaluate how obesity treatment strategies can improve risk factors and, ultimately, adverse clinical outcomes.

  View details for DOI 10.1038/nrcardio.2011.86

  View details for Web of Science ID 000294202200005

  View details for PubMedID 21670745

  View details for PubMedCentralID PMC4292916

• Uric Acid as a Mediator of Diabetic Nephropathy SEMINARS IN NEPHROLOGY Jalal, D. I., Maahs, D. M., Hovind, P., Nakagawa, T. 2011; 31 (5): 459-465

  Abstract

  Despite advances in the management of patients with diabetes, diabetic nephropathy (DN) remains the most common cause of end-stage renal disease in the United States and worldwide. Inflammation and endothelial dysfunction appear to play a central role in the onset and the progression of DN. Recent evidence has emerged in the past decade to suggest uric acid is an inflammatory factor and may play a role in endothelial dysfunction. This has lead our group and others to explore the role of uric acid in the onset and progression of DN. In this review, we highlight some of the animal and human studies that implicate uric acid in DN. Based on the evidence we review, we conclude the need for properly planned randomized controlled studies to decrease uric acid levels and assess the impact of such therapy on diabetic kidney disease.

  View details for DOI 10.1016/j.semnephrol.2011.08.011

  View details for Web of Science ID 000296486700011

  View details for PubMedID 22000654

  View details for PubMedCentralID PMC3197214

• Prevention of Overweight/Obesity as a Strategy to Optimize Cardiovascular Health CIRCULATION Cornier, M., Marshall, J. A., Hill, J. O., Maahs, D. M., Eckel, R. H. 2011; 124 (7): 840-850

  View details for DOI 10.1161/CIRCULATIONAHA.110.968461

  View details for Web of Science ID 000293884900020

  View details for PubMedID 21844090

• Systematic Shifts in Cystatin C Between 2006 and 2010 CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY Maahs, D. M., Jalal, D., McFann, K., Rewers, M., Snell-Bergeon, J. K. 2011; 6 (8): 1952-1955

  Abstract

  Cystatin C is used increasingly as a biomarker of renal function; however, cystatin C assays are not standardized. Our objective was to compare cystatin C results within the Coronary Artery Calcification in Type 1 Diabetes (CACTI) study over time and in repeated measures to evaluate for assay drift.Serum samples were obtained at baseline (visit 1 [V1], 2000 to 2002) and follow-up (visit 2 [V2], 2003 to 2005; visit 3 [V3], 2006 to 2008) and were assayed in 2006 (V1), 2007 to 2008 (V2), and 2010 (V3) in the same laboratory.Mean cystatin C levels measured using the Dade-Behring assay decreased over time in subjects, with measures at all three visits (V1: 0.80 ± 0.19 [0.42 to 3.41], V2: 0.75 ± 0.22 [0.39 to 3.77], and V3: 0.69 ± 0.22 [0.39 to 3.79]). Cystatin C values were lower in V1 and V2 samples remeasured in 2010 (mean differences -0.13 ± 0.04 and -0.08 ± 0.04, P < 0.0001 for both). Correlations for original and re-run values were strong for V1 (r = 0.99) and V2 (r = 0.99). Deming regression equations and Bland-Altman plots suggest a systematic shift in the values over time.Systematic shifts in cystatin C levels, which can be corrected by regression adjustment, occurred in our laboratory in samples measured in 2006 and 2007 to 2008 as compared with 2010. Assay standardization and measurement reliability for cystatin C must be addressed.

  View details for DOI 10.2215/CJN.11271210

  View details for Web of Science ID 000293721400023

  View details for PubMedID 21784814

  View details for PubMedCentralID PMC3156426

• Lipoprotein-Associated Phospholipase A(2) Activity Predicts Progression of Subclinical Coronary Atherosclerosis DIABETES TECHNOLOGY & THERAPEUTICS Kinney, G. L., Snell-Bergeon, J. K., Maahs, D. M., Eckel, R. H., Ehrlich, J., Rewers, M., Hokanson, J. E. 2011; 13 (3): 381-387

  Abstract

  Lipoprotein-associated phospholipase A? (Lp-PLA?) is a lipoprotein-associated enzyme that cleaves oxidized phosphatidylcholines, generating pro-atherosclerotic lysophosphatidylcholine and oxidized free fatty acids. Lp-PLA? is independently associated with cardiovascular disease (CVD) in a variety of populations. Coronary calcium is a measure of subclinical CVD, and progression of coronary calcification predicts future CVD events. In type 1 diabetes there is an increase in coronary calcium and CVD despite a favorable lipid profile. Levels of Lp-PLA? in type 1 diabetes are not known, nor is the relationship between Lp-PLA? and progression of coronary calcification.The Coronary Artery Calcification in Type 1 Diabetes study measured coronary calcium by electron-beam computed tomography twice over a 2.6 ± 0.3-year interval. Lp-PLA? mass and activity were measured at baseline (n = 1,097 subjects, 506 with and 591 without type 1 diabetes).In type 1 diabetes Lp-PLA? mass was marginally higher (285 ± 79 vs. 278 ± 78 ng/mL, P = 0.1), and Lp-PLA? activity was significantly lower (137 ± 30 vs. 146?±?36 nmol/min/mL, P < 0.0001) than in those without diabetes. There was a greater proportion of those with progression of coronary calcification in type 1 diabetes compared with those without diabetes (24% vs. 10%, P < 0.0001). Lp-PLA? activity was independently associated with progression of coronary calcification in multivariate analysis (4th quartile verses bottom three quartiles, odds ratio?=?1.77 [1.08-2.91], P = 0.02). LpPLA? mass was not significantly associated with progression of coronary calcification in this cohort (P = 0.09).Lp-PLA? activity predicts progression of subclinical atherosclerosis in individuals with and without type 1 diabetes.

  View details for DOI 10.1089/dia.2010.0175

  View details for Web of Science ID 000287798200013

  View details for PubMedID 21291330

  View details for PubMedCentralID PMC3101921

• Correlates of Dietary Intake in Youth with Diabetes: Results from the SEARCH for Diabetes in Youth Study JOURNAL OF NUTRITION EDUCATION AND BEHAVIOR Bortsov, A., Liese, A. D., Bell, R. A., Dabelea, D., D'Agostino, R. B., Hamman, R. F., Klingensmith, G. J., Lawrence, J. M., Maahs, D. M., McKeown, R., Marcovina, S. M., Thomas, J., Mayer-Davis, E. J. 2011; 43 (2): 123-129

  Abstract

  To explore demographic, socioeconomic, diabetes-related, and behavioral correlates of dietary intake of dairy, fruit, vegetables, sweetened soda, fiber, calcium, and saturated fat in youth with diabetes.Cross-sectional study of youth 10-22 years old with type 1 (T1DM, n = 2,176) and type 2 diabetes (T2DM, n = 365). Association of dietary intake, demographics, socioeconomic status, behavioral, and diabetes-related measures was explored with quantile regression.T1DM males had lower consumption of vegetables, fruit, and fiber, and higher consumption of soda and saturated fat than females (P < .01). African Americans had lower dairy and higher soda intake than non-Hispanic T1DM whites (P < .01). Soda consumption was higher in older T2DM youth than in younger participants (P < .01). Lifestyle and physical activity patterns were also significantly associated with dietary intake.Identified demographic and behavioral correlates may help dietitians to focus on groups of youth with diabetes who have lower adherence to a healthful diet. Diet counseling groups may be tailored according to these major determinants.

  View details for DOI 10.1016/j.jneb.2009.12.007

  View details for Web of Science ID 000288307200009

  View details for PubMedID 21276755

  View details for PubMedCentralID PMC3055946

• Association of insulin sensitivity to lipids across the lifespan in people with Type 1 diabetes DIABETIC MEDICINE Maahs, D. M., Nadeau, K., Snell-Bergeon, J. K., Schauer, I., Bergman, B., West, N. A., Rewers, M., Daniels, S. R., Ogden, L. G., Hamman, R. F., Dabelea, D. 2011; 28 (2): 148-155

  Abstract

  Insulin resistance and dyslipidaemia both increase cardiovascular risk in Type 1 diabetes. However, little data exist on the associations of insulin resistance to lipids in Type 1 diabetes. Our objective was to explore the associations between insulin resistance (assessed by glucose infusion rate) and lipids in people with Type 1 diabetes and determine whether adiposity and/or average glycaemia influence these associations.Hyperinsulinaemic-euglycaemic clamp studies were performed in 60 subjects with Type 1 diabetes aged 12-19 years (age 15±2 years, 57% female, duration of diabetes 6.3±3.8 years, HbA(1c) 8.6±1.5%, IFCC=70 mmol/mol) and 40 subjects with Type 1 diabetes aged 27-61 years (age 45±9 years, 53% female, duration of diabetes 23±8 years, HbA(1c) 7.5±0.9%, IFCC=58 mmol/mol). Multiple linear regression models were fit to examine the association between glucose infusion rate and fasting lipid levels with adjustment for possible confounders.Lower glucose infusion rate was significantly associated with lower levels of HDL cholesterol in youths with Type 1 diabetes and with higher levels of triglycerides and higher triglyceride/HDL ratio in both youths and adults. The magnitude of the associations between glucose infusion rate and lipid levels translate into interquartile differences of 0.098 mmol/l for HDL cholesterol, 0.17 mmol/l for triglycerides and 1.06 for triglycerides/HDL in the adolescents and 0.20 mmol/l for triglycerides and 1.01 for triglycerides/HDL in the adults. The associations were attenuated and no longer statistically significant by adjustment for adiposity among adults, while adjustment for HbA(1c) had a small effect in youths and adults.Lower insulin sensitivity is associated with a more atherogenic lipid profile in both youths and adults with Type 1 diabetes.

  View details for DOI 10.1111/j.1464-5491.2010.03143.x

  View details for Web of Science ID 000286107000004

  View details for PubMedID 21219421

  View details for PubMedCentralID PMC3395467

• Angiogenic growth factors correlate with disease severity in young patients with autosomal dominant polycystic kidney disease KIDNEY INTERNATIONAL Reed, B. Y., Masoumi, A., Elhassan, E., McFann, K., Cadnapaphornchai, M. A., Maahs, D. M., Snell-Bergeon, J. K., Schrier, R. W. 2011; 79 (1): 128-134

  Abstract

  Renal cysts, pain, and hematuria are common presentations of autosomal dominant polycystic kidney disease (ADPKD) in children. Renal function, however, is typically preserved in these patients despite increased renal volume. Since angiogenesis has been implicated in promotion of renal cyst growth in ADPKD, we measured the serum level of various angiogenic factors and early renal structural changes and cardiovascular parameters in 71 patients with ADPKD, with a mean age of 16 years. Renal structure and left ventricular mass index were measured by magnetic resonance imaging or by echocardiogram. Renal function was assessed by creatinine clearance and urinary protein excretion. Serum growth factor levels were measured by enzyme-linked immunosorbent assay. Because of skewed distributions, the various parameters are reported as log(10). Serum log(10) vascular endothelial growth factor was positively correlated with renal and cardiac structure, but negatively with creatinine clearance. Serum angiopoietin 1 levels significantly correlated with structural change in both the kidney and the heart and with urinary protein. Thus, the correlation between angiogenic growth factors with both renal and cardiac disease severity is compatible with a possible role for angiogenesis in the early progression of disease in ADPKD.

  View details for DOI 10.1038/ki.2010.355

  View details for Web of Science ID 000285334100015

  View details for PubMedID 20881939

  View details for PubMedCentralID PMC3815472

• Insulin Resistance, Defective Insulin-Mediated Fatty Acid Suppression, and Coronary Artery Calcification in Subjects With and Without Type 1 Diabetes The CACTI Study DIABETES Schauer, I. E., Snell-Bergeon, J. K., Bergman, B. C., Maahs, D. M., Kretowski, A., Eckel, R. H., Rewers, M. 2011; 60 (1): 306-314

  Abstract

  To assess insulin action on peripheral glucose utilization and nonesterified fatty acid (NEFA) suppression as a predictor of coronary artery calcification (CAC) in patients with type 1 diabetes and nondiabetic controls.Insulin action was measured by a three-stage hyperinsulinemic-euglycemic clamp (4, 8, and 40 mU/m²/min) in 87 subjects from the Coronary Artery Calcification in Type 1 Diabetes cohort (40 diabetic, 47 nondiabetic; mean age 45 ± 8 years; 55% female).Peripheral glucose utilization was lower in subjects with type 1 diabetes compared with nondiabetic controls: glucose infusion rate (mg/kg FFM/min) = 6.19 ± 0.72 vs. 12.71 ± 0.66, mean ± SE, P < 0.0001, after adjustment for age, sex, BMI, fasting glucose, and final clamp glucose and insulin. Insulin-induced NEFA suppression was also lower in type 1 diabetic compared with nondiabetic subjects: NEFA levels (?M) during 8 mU/m²/min insulin infusion = 370 ± 27 vs. 185 ± 25, P < 0.0001, after adjustment for age, sex, BMI, fasting glucose, and time point insulin. Lower glucose utilization and higher NEFA levels, correlated with CAC volume (r = -0.42, P < 0.0001 and r = 0.41, P < 0.0001, respectively) and predicted the presence of CAC (odds ratio [OR] = 0.45, 95% CI = 0.22-0.93, P = 0.03; OR = 2.4, 95% CI = 1.08-5.32, P = 0.032, respectively). Insulin resistance did not correlate with GHb or continuous glucose monitoring parameters.Type 1 diabetic patients are insulin resistant compared with nondiabetic subjects, and the degree of resistance is not related to current glycemic control. Insulin resistance predicts the extent of coronary artery calcification and may contribute to the increased risk of cardiovascular disease in patients with type 1 diabetes as well as subjects without diabetes.

  View details for DOI 10.2337/db10-0328

  View details for Web of Science ID 000286017300037

  View details for PubMedID 20978091

  View details for PubMedCentralID PMC3012187

• Development, validation and use of an insulin sensitivity score in youths with diabetes: the SEARCH for Diabetes in Youth study DIABETOLOGIA Dabelea, D., D'Agostino, R. B., Mason, C. C., West, N., Hamman, R. F., Mayer-Davis, E. J., Maahs, D., Klingensmith, G., Knowler, W. C., Nadeau, K. 2011; 54 (1): 78-86

  Abstract

  The ability to measure insulin sensitivity across the phenotypic spectrum of diabetes may contribute to a more accurate characterisation of diabetes type. Our goal was to develop and validate an insulin sensitivity (IS) score using the euglycaemic-hyperinsulinaemic clamp in a subset (n?=?85) of 12- to 19-year-old youths with diabetes participating in the SEARCH study in Colorado, USA.Youths with a diagnosis of type 1 (n?=?60) or type 2 diabetes (n?=?25) underwent a 3 h clamp to measure glucose disposal rate (GDR, mg kg?¹ min?¹). Demographic (age, sex, race), clinical (BMI, waist, Tanner stage) and metabolic characteristics (HbA?(c), lipids, blood pressure, urine albumin:creatinine) were used to estimate log(e)IS score via stepwise linear regression on a model-development set (n?=?53). Estimated IS score was evaluated for reproducibility on two validation sets: youths with diabetes (n?=?33) and healthy control youths (n?=?22).The best model included waist, triacylglycerol (TG) and HbA?(c) levels (R²?=?0.74). Diabetes type did not enter the model and there were no significant interactions between diabetes type and other predictors. Estimated IS score correlated well (r?=?0.65, p?

  View details for DOI 10.1007/s00125-010-1911-9

  View details for Web of Science ID 000284896900014

  View details for PubMedID 20886205

• Report of the 36th ISPAD meeting, Buenos Aires, Argentina, 27-30 October 2010 PEDIATRIC DIABETES Benitez-Aguirre, P., Maahs, D. M. 2010; 11 (8): 583-591

  View details for DOI 10.1111/j.1399-5448.2010.00746.x

  View details for Web of Science ID 000284854900012

  View details for PubMedID 21118343

• Glycaemic variability is associated with coronary artery calcium in men with Type 1 diabetes: the Coronary Artery Calcification in Type 1 Diabetes study DIABETIC MEDICINE Snell-Bergeon, J. K., Roman, R., Rodbard, D., Garg, S., Maahs, D. M., Schauer, I. E., Bergman, B. C., Kinney, G. L., Rewers, M. 2010; 27 (12): 1436-1442

  Abstract

  We investigated coronary artery calcium in association with glucose levels and variability measured using continuous glucose monitoring in adults with Type 1 diabetes in the Coronary Artery Calcification in Type 1 Diabetes study.Coronary artery calcium was measured by electron beam tomography. The presence of any coronary artery calcium was analysed with respect to glucose levels [mean(T) (mean glucose), % of values < 3.9 mmol/l, > 10 mmol/l and either < 3.9 or > 10 mmol/l] and glycaemic variability [sd(T) (sd of all glucose values); sd(dm) (sd of the daily mean glucose levels) and sd(hh:mm) (glucose sd for a specified time of day, over all days)] using 3-5 days of continuous glucose monitoring from 75 subjects (45 women, 30 men), age 42 ± 9 years (mean ± sd) and diabetes duration of 29 ± 8 years using logistic regression.We observed significant associations between coronary artery calcium and mean(T) (OR = 4.4, 95% CI 1.1-18.6), % of values > 10 mmol/l (OR = 5.5, 95% CI 1.3-22.6), % of measures < 3.9 or > 10 mmol/l (OR = 5.7, 95% CI 1.3-24.9), sd(T) (OR = 4.7, 95% CI 1.1-19.7), sd(dm) (OR = 6.0, 95% CI 1.2-30.4) and sd(hh:mm) (OR = 4.0, 95% CI 1.1-15.4), among men, but none of these variables were associated with the presence of coronary artery calcium in women.We report the novel finding that subclinical atherosclerosis is associated with glucose levels and variability in men with Type 1 diabetes. The relationship of coronary artery calcium and glucose variability in Type 1 diabetes, and potential gender differences in this association, deserve further study.

  View details for DOI 10.1111/j.1464-5491.2010.03127.x

  View details for Web of Science ID 000284070400014

  View details for PubMedID 21059097

  View details for PubMedCentralID PMC3052953

• Association of glycaemia with lipids in adults with type 1 diabetes: modification by dyslipidaemia medication DIABETOLOGIA Maahs, D. M., Ogden, L. G., Dabelea, D., Snell-Bergeon, J. K., Daniels, S. R., Hamman, R. F., Rewers, M. 2010; 53 (12): 2518-2525

  Abstract

  Hyperglycaemia and dyslipidaemia are common metabolic abnormalities in adults with type 1 diabetes and both increase cardiovascular disease (CVD) risk. The hypothesis of this study was that change in HbA(1c) over 6 years would be associated with change in fasting lipids in adults with type 1 diabetes.The Coronary Artery Calcification in Type 1 Diabetes (CACTI) study examined 652 patients with type 1 diabetes (54% female); 559 and 543 had follow-up visits at 3 and 6 years. Baseline age (mean ± SD) was 37 ± 9 years, diabetes duration 23 ± 9 years, and HbA(1c) 8.0 ± 1.3%. Use of dyslipidaemia medication was 17%, 32%, and 46% at the three visits. Separate longitudinal mixed models were fitted to examine the relationship between change in HbA(1c) and change in fasting total cholesterol (TC), HDL-cholesterol (HDL-c), LDL-cholesterol (LDL-c), log triacylglycerols (TG), and non-HDL-cholesterol (non-HDL-c). Because of an interaction between dyslipidaemia medication use and association of HbA(1c) with lipids, results were stratified by dyslipidaemia medication use.Among patients not using dyslipidaemia medication, a higher HbA(1c) was associated with significantly worse levels of the lipids TC, LDL-c, TG and non-HDL-c (per 1% change in HbA1c, TC 0.101 mmol/l, 95% CI 0.050, 0.152; LDL-c 0.103 mmol/l, 95% CI 0.058, 0.148; TG 0.052 mmol/l, 95% CI 0.024, 0.081; and non-HDL-c 0.129 mmol/l, 95% CI 0.078, 0.180) but not HDL-c (-0.20 mmol/l, 95% CI -0.047, 0.007). The associations between HbA(1c) and any lipid outcome among those on dyslipidaemia medication were in the same direction, but attenuated compared with persons not on medication.Change in HbA(1c) is significantly associated with change in fasting lipids, but dyslipidaemia medications may be required to optimise lipid and cardiovascular health.

  View details for DOI 10.1007/s00125-010-1886-6

  View details for Web of Science ID 000284509900009

  View details for PubMedID 20820753

  View details for PubMedCentralID PMC3405233

• Serum Uric Acid Predicts Progression of Subclinical Coronary Atherosclerosis in Individuals Without Renal Disease DIABETES CARE Rodrigues, T. C., Maahs, D. M., Johnson, R. J., Jalal, D. I., Kinney, G. L., Rivard, C., Rewers, M., Snell-Bergeon, J. K. 2010; 33 (11): 2471-2473

  Abstract

  To examine uric acid (UA) as a possible predictor of the progression of coronary artery calcification (CAC) using data from the prospective Coronary Artery Calcification in Type 1 Diabetes (CACTI) Study.CAC was measured by electron beam tomography at the baseline and at a follow-up 6.0±0.5 years later. The study population included 443 participants with type 1 diabetes and 526 control subjects who were free of diagnosed coronary artery disease at baseline. The presence of renal disease was defined by the presence of albuminuria and/or low glomerular filtration rate.In subjects without renal disease, serum UA predicted CAC progression (odds ratio 1.30 [95% CI 1.07-1.58], P=0.007) independent of conventional cardiovascular risk factors including diabetes and the presence of metabolic syndrome.Serum UA levels predict the progression of coronary atherosclerosis and may be useful in identifying who is at risk for vascular disease in the absence of significant chronic kidney disease.

  View details for DOI 10.2337/dc10-1007

  View details for Web of Science ID 000284516400034

  View details for PubMedID 20798338

  View details for PubMedCentralID PMC2963516

• Urinary proteomic diagnosis of coronary artery disease: identification and clinical validation in 623 individuals JOURNAL OF HYPERTENSION Delles, C., Schiffer, E., von zur Muhlen, C., Peter, K., Rossing, P., Parving, H., Dymott, J. A., Neisius, U., Zimmerli, L. U., Snell-Bergeon, J. K., Maahs, D. M., Schmieder, R. E., Mischak, H., Dominiczak, A. F. 2010; 28 (11): 2316-2322

  Abstract

  We studied the urinary proteome in a total of 623 individuals with and without coronary artery disease (CAD) in order to characterize multiple biomarkers that enable prediction of the presence of CAD.Urine samples were analyzed by capillary electrophoresis coupled online to micro time-of-flight mass spectrometry.We defined a pattern of 238 CAD-specific polypeptides from comparison of 586 spot urine samples from 408 individuals. This pattern identified patients with CAD in a blinded cohort of 138 urine samples (71 patients with CAD and 67 healthy individuals) with high sensitivity and specificity (area under the receiver operator characteristic curve 87%, 95% confidence interval 81-92) and was superior to previously developed 15-marker (area under the receiver operator characteristic curve 68%, P < 0.0001) and 17-marker panels (area under the receiver operator characteristic curve 77%, P < 0.0001). The sequences of the discriminatory polypeptides include fragments of alpha-1-antitrypsin, collagen types 1 and 3, granin-like neuroendocrine peptide precursor, membrane-associated progesterone receptor component 1, sodium/potassium-transporting ATPase gamma chain and fibrinogen-alpha chain. Several biomarkers changed significantly toward the healthy signature following 2-year treatment with irbesartan, whereas short-term treatment with irbesartan did not significantly affect the polypeptide pattern.Urinary proteomics identifies CAD with high confidence and might also be useful for monitoring the effects of therapeutic interventions.

  View details for DOI 10.1097/HJH.0b013e32833d81b7

  View details for Web of Science ID 000282987000020

  View details for PubMedID 20811296

• Urinary Collagen Fragments Are Significantly Altered in Diabetes: A Link to Pathophysiology PLOS ONE Maahs, D. M., Siwy, J., Argiles, A., Cerna, M., Delles, C., Dominiczak, A. F., Gayrard, N., Iphoefer, A., Jaensch, L., Jerums, G., Medek, K., Mischak, H., Navis, G. J., Roob, J. M., Rossing, K., Rossing, P., Rychlik, I., Schiffer, E., Schmieder, R. E., Wascher, T. C., Winklhofer-Roob, B. M., Zimmerli, L. U., Zuerbig, P., Snell-Bergeon, J. K. 2010; 5 (9)

  Abstract

  The pathogenesis of diabetes mellitus (DM) is variable, comprising different inflammatory and immune responses. Proteome analysis holds the promise of delivering insight into the pathophysiological changes associated with diabetes. Recently, we identified and validated urinary proteomics biomarkers for diabetes. Based on these initial findings, we aimed to further validate urinary proteomics biomarkers specific for diabetes in general, and particularity associated with either type 1 (T1D) or type 2 diabetes (T2D).Therefore, the low-molecular-weight urinary proteome of 902 subjects from 10 different centers, 315 controls and 587 patients with T1D (n = 299) or T2D (n = 288), was analyzed using capillary-electrophoresis mass-spectrometry. The 261 urinary biomarkers (100 were sequenced) previously discovered in 205 subjects were validated in an additional 697 subjects to distinguish DM subjects (n = 382) from control subjects (n = 315) with 94% (95% CI: 92-95) accuracy in this study. To identify biomarkers that differentiate T1D from T2D, a subset of normoalbuminuric patients with T1D (n = 68) and T2D (n = 42) was employed, enabling identification of 131 biomarker candidates (40 were sequenced) differentially regulated between T1D and T2D. These biomarkers distinguished T1D from T2D in an independent validation set of normoalbuminuric patients (n = 108) with 88% (95% CI: 81-94%) accuracy, and in patients with impaired renal function (n = 369) with 85% (95% CI: 81-88%) accuracy. Specific collagen fragments were associated with diabetes and type of diabetes indicating changes in collagen turnover and extracellular matrix as one hallmark of the molecular pathophysiology of diabetes. Additional biomarkers including inflammatory processes and pro-thrombotic alterations were observed.These findings, based on the largest proteomic study performed to date on subjects with DM, validate the previously described biomarkers for DM, and pinpoint differences in the urinary proteome of T1D and T2D, indicating significant differences in extracellular matrix remodeling.

  View details for DOI 10.1371/journal.pone.0013051

  View details for Web of Science ID 000282210700021

  View details for PubMedID 20927192

  View details for PubMedCentralID PMC2946909

• Epidemiology of Type 1 Diabetes ENDOCRINOLOGY AND METABOLISM CLINICS OF NORTH AMERICA Maahs, D. M., West, N. A., Lawrence, J. M., Mayer-Davis, E. J. 2010; 39 (3): 481-?

  Abstract

  This article describes the epidemiology of type 1 diabetes mellitus (T1D) around the world and across the lifespan. Epidemiologic patterns of T1D by demographic, geographic, biologic, cultural, and other factors in populations are presented to gain insight about the causes, natural history, risks, and complications of T1D. Data from large epidemiologic studies worldwide indicate that the incidence of T1D has been increasing by 2% to 5% worldwide and that the prevalence of T1D is approximately 1 in 300 in the United States by 18 years of age. Research on risk factors for T1D is an active area of research to identify genetic and environmental triggers that could potentially be targeted for intervention. Although significant advances have been made in the clinical care of T1D with resultant improvements in quality of life and clinical outcomes, much more needs to be done to improve care of, and ultimately find a cure for, T1D. Epidemiologic studies have an important ongoing role to investigate the complex causes, clinical care, prevention, and cure of T1D.

  View details for DOI 10.1016/j.ecl.2010.05.011

  View details for Web of Science ID 000282146100003

  View details for PubMedID 20723815

  View details for PubMedCentralID PMC2925303

• Lipoprotein Subfraction Cholesterol Distribution Is Proatherogenic in Women With Type 1 Diabetes and Insulin Resistance DIABETES Maahs, D. M., Hokanson, J. E., Wang, H., Kinney, G. L., Snell-Bergeon, J. K., East, A., Bergman, B. C., Schauer, I. E., Rewers, M., Eckel, R. H. 2010; 59 (7): 1771-1779

  Abstract

  Individuals with type 1 diabetes have a less atherogenic fasting lipid profile than those without diabetes but paradoxically have increased rates of cardiovascular disease (CVD). We investigated differences in lipoprotein subfraction cholesterol distribution and insulin resistance between subjects with and without type 1 diabetes to better understand the etiology of increased CVD risk.Fast protein liquid chromatography was used to fractionate lipoprotein cholesterol distribution in a substudy of the Coronary Artery Calcification in Type 1 Diabetes (CACTI) study (n = 82, age 46 +/- 8 years, 52% female, 49% with type 1 diabetes for 23 +/- 8 years). Insulin resistance was assessed by a hyperinsulinemic-euglycemic clamp.Among men, those with type 1 diabetes had less VLDL and more HDL cholesterol than control subjects (P < 0.05), but among women, those with diabetes had a shift in cholesterol to denser LDL, despite more statin use. Among control subjects, men had more cholesterol distributed as VLDL and LDL but less as HDL than women; however, among those with type 1 diabetes, there was no sex difference. Within sex and diabetes strata, a more atherogenic cholesterol distribution by insulin resistance was seen in men with and without diabetes, but only in women with type 1 diabetes.The expected sex-based less atherogenic lipoprotein cholesterol distribution was not seen in women with type 1 diabetes. Moreover, insulin resistance was associated with a more atherogenic lipoprotein cholesterol distribution in all men and in women with type 1 diabetes. This lipoprotein cholesterol distribution may contribute to sex-based differences in CVD in type 1 diabetes.

  View details for DOI 10.2337/db09-1626

  View details for Web of Science ID 000279615100027

  View details for PubMedID 20393149

  View details for PubMedCentralID PMC2889778

• Metabolic Screening in Children Receiving Antipsychotic Drug Treatment (vol 164, pg 344, 2010) ARCHIVES OF PEDIATRICS & ADOLESCENT MEDICINE Morrato, E. H., Nicol, G. E., Maahs, D., Druss, B. G., Hartung, D. M., Valuck, R. J., Campagna, E., Newcomer, J. W. 2010; 164 (6): 584-584

  View details for Web of Science ID 000278324300018

• Serum uric acid levels predict the development of albuminuria over 6 years in patients with type 1 diabetes: findings from the Coronary Artery Calcification in Type 1 Diabetes study NEPHROLOGY DIALYSIS TRANSPLANTATION Jalal, D. I., Rivard, C. J., Johnson, R. J., Maahs, D. M., McFann, K., Rewers, M., Snell-Bergeon, J. K. 2010; 25 (6): 1865-1869

  Abstract

  Recent studies suggest that uric acid is a mediator of diabetic nephropathy. We hypothesized that elevated serum uric acid levels are a strong predictor of albuminuria in patients with type 1 diabetes.We analyzed data from the Coronary Artery Calcification in Type 1 Diabetes study, a prospective observational study. A stepwise logistic regression model was applied to predict the development of micro- or macroalbuminuria after 6 years of follow-up in 324 participants who had no evidence of micro- or macroalbuminuria at baseline. A P-value <0.1 was used as the criteria for entry into and removal from the model.The following factors were selected in the stepwise multivariate model as predictors of micro- or macroalbuminuria at the 6-year follow-up visit: baseline serum uric acid levels, HbA(1c) and pre-albuminuria. For every 1-mg/dl increase in serum uric acid levels at baseline, there was an 80% increased risk of developing micro- or macroalbuminuria at 6 years (odds ratio 1.8; 95% confidence interval 1.2, 2.8; P = 0.005). Additional covariates considered in the stepwise model were sex, age, duration of diabetes, angiotensin-converting enzyme inhibitor or angiotensin II receptor blocker treatment, waist circumference, waist/hip ratio, body mass index, systolic and diastolic blood pressure, smoking, serum creatinine, cystatin C, high-density lipoprotein cholesterol and triglycerides.Elevated serum uric acid levels are a strong predictor of the development of albuminuria in patients with type 1 diabetes.

  View details for DOI 10.1093/ndt/gfp740

  View details for Web of Science ID 000280027400025

  View details for PubMedID 20064950

  View details for PubMedCentralID PMC2902891

• The Use of Insulin Pumps in Youth with Type 1 Diabetes DIABETES TECHNOLOGY & THERAPEUTICS Maahs, D. M., Horton, L. A., Chase, H. P. 2010; 12: S59-S65

  Abstract

  The use of insulin pump therapy (continuous subcutaneous insulin infusion) has increased dramatically in youth with type 1 diabetes (T1D) in the past decade. In this review we provide background and practical clinical advice on insulin basal rates and bolus doses and on the advantages of pump therapy with exercise. Acute complications of T1D (hypoglycemia and diabetic ketoacidosis) in the context of pump therapy are reviewed. The advantages of pump therapy in the school setting and in hospitalized patients are discussed. Finally, diabetes management in the 21st century, in which pump therapy is combined with continuous glucose monitoring, and its potential for a closed-loop pancreas are presented.

  View details for DOI 10.1089/dia.2009.0161

  View details for Web of Science ID 000278212300011

  View details for PubMedID 20515309

  View details for PubMedCentralID PMC2936259

• Higher Fibrinogen Levels Predict Progression of Coronary Artery Calcification in Adults with Type 1 Diabetes ATHEROSCLEROSIS Rodrigues, T. C., Snell-Bergeon, J. K., Maahs, D. M., Kinney, G. L., Rewers, M. 2010; 210 (2): 671-673

  Abstract

  To determine whether fibrinogen levels predict independently progression of coronary artery calcification (CAC) in adults with type 1 diabetes.Data from a prospective cohort--the Coronary Artery Calcification in Type 1 Diabetes Study--were evaluated. Fibrinogen levels at baseline were separated into quartiles. CAC was measured twice and averaged at baseline and at follow-up 2.4+/-0.4 years later. CAC progressors were defined as participants whose square-root transformed CAC volume increased by >or=2.5 mm3 or development of clinical coronary artery disease during the follow-up period.Fibrinogen levels were higher in progressors than in non-progressors (276+/-61 mg/dl versus 259+/-61 mg/dl, p=0.0003). CAC progression, adjusted for known cardiovascular risk factors, increased in the highest quartile.Higher fibrinogen levels predict CAC progression in type 1 diabetes subjects, independent of standard cardiovascular risk factors.

  View details for DOI 10.1016/j.atherosclerosis.2009.12.034

  View details for Web of Science ID 000278036800059

  View details for PubMedID 20079495

  View details for PubMedCentralID PMC2896570

• Metabolic Screening in Children Receiving Antipsychotic Drug Treatment ARCHIVES OF PEDIATRICS & ADOLESCENT MEDICINE Morrato, E. H., Nicol, G. E., Maahs, D., Druss, B. G., Hartung, D. M., Valuck, R. J., Campagna, E., Newcomer, J. W. 2010; 164 (4): 344-351

  Abstract

  To estimate metabolic screening rates, predictors of screening, and incidence of metabolic disturbances in children initiating second-generation antipsychotic (SGA) drug treatment.A retrospective, new-user cohort study (between July 1, 2004, and June 30, 2006) using Medicaid claims data.California, Missouri, and Oregon.A total of 5370 children (aged 6-17 years) without diabetes mellitus taking SGA drugs and 15,000 children without diabetes taking albuterol (control individuals) [corrected] but no SGA drugs.Findings 1 year after recommendations from the American Diabetes Association and American Psychiatric Association called for metabolic screening of patients receiving SGA drugs.Serum glucose and lipid testing, 6-month incidence of diabetes, and dyslipidemia disturbances.Glucose screening was performed in 1699 (31.6% [95% confidence interval (CI), 30.4%-32.9%]) SGA-treated children vs 1891 (12.6% [12.1%-13.2%]) control individuals. Lipid testing was performed in 720 (13.4% [95% CI, 12.5%-14.4%]) SGA-treated children vs 458 (3.1% [2.8%-3.3%]) controls. In multivariate logistic regression analysis, children with serious and/or multiple psychiatric diagnoses and those who used health care services more intensively were more likely to receive metabolic screening. The case incidence of glucose and lipid disorders was higher in SGA-treated vs albuterol-treated children (8.9 per 1000 children [95% CI, 6.6%-11.8%] vs 4.9 per 1000 children [3.9%-6.2%]; and 9.7 per 1000 children [95% CI, 7.2%-12.7%] vs 4.6 per 1000 children [95% CI, 3.6%-5.8%], respectively).Most children starting treatment with SGA medications in this public sector sample did not receive recommended glucose and lipid screening.

  View details for Web of Science ID 000276312700008

  View details for PubMedID 20368487

• Progression to microalbuminuria in type 1 diabetes: development and validation of a prediction rule DIABETOLOGIA Vergouwe, Y., Soedamah-Muthu, S. S., Zgibor, J., Chaturvedi, N., Forsblom, C., Snell-Bergeon, J. K., Maahs, D. M., Groop, P., Rewers, M., Orchard, T. J., Fuller, J. H., Moons, K. G. 2010; 53 (2): 254-262

  Abstract

  Microalbuminuria is common in type 1 diabetes and is associated with an increased risk of renal and cardiovascular disease. We aimed to develop and validate a clinical prediction rule that estimates the absolute risk of microalbuminuria.Data from the European Diabetes Prospective Complications Study (n = 1115) were used to develop the prediction rule (development set). Multivariable logistic regression analysis was used to assess the association between potential predictors and progression to microalbuminuria within 7 years. The performance of the prediction rule was assessed with calibration and discrimination (concordance statistic [c-statistic]) measures. The rule was validated in three other diabetes studies (Pittsburgh Epidemiology of Diabetes Complications [EDC] study, Finnish Diabetic Nephropathy [FinnDiane] study and Coronary Artery Calcification in Type 1 Diabetes [CACTI] study).Of patients in the development set, 13% were microalbuminuric after 7 years. Glycosylated haemoglobin, AER, WHR, BMI and ever smoking were found to be the most important predictors. A high-risk group (n = 87 [8%]) was identified with a risk of progression to microalbuminuria of 32%. Predictions showed reasonable discriminative ability, with c-statistic of 0.71. The rule showed good calibration and discrimination in EDC, FinnDiane and CACTI (c-statistic 0.71, 0.79 and 0.79, respectively).We developed and validated a clinical prediction rule that uses relatively easily obtainable patient characteristics to predict microalbuminuria in patients with type 1 diabetes. This rule can help clinicians to decide on more frequent check-ups for patients at high risk of microalbuminuria in order to prevent long-term chronic complications.

  View details for DOI 10.1007/s00125-009-1585-3

  View details for Web of Science ID 000273084400006

  View details for PubMedID 19908023

  View details for PubMedCentralID PMC2797626

• Oral Health Knowledge and Behaviors among Adolescents with Type 1 Diabetes. International journal of dentistry Orlando, V. A., Johnson, L. R., Wilson, A. R., Maahs, D. M., Wadwa, R. P., Bishop, F. K., Dong, F., Morrato, E. H. 2010; 2010: 942124-?

  Abstract

  Early onset and more advanced periodontal disease has been reported for children with diabetes. We surveyed oral health knowledge, attitudes, and behaviors among adolescents with diabetes in order to inform potential intervention strategies. Study subjects were youth (ages 12-19 years) with type 1 diabetes (N = 90) participating in a cohort study investigating determinants of periodontal disease at a regional pediatric diabetes specialty clinic. Over 90% of the youth had been instructed on how to brush and floss and had preventive dental care in the past year. However, 44% knew that periodontal disease is associated with diabetes and 32% knew that it can start in childhood with bleeding gums. Despite being at high risk for developing periodontal disease, the mean toothbrushing frequency was once per day and 42% did not floss. Significant opportunity exists for improving periodontal disease knowledge and adoption of preventive oral hygiene behaviors in adolescents with diabetes.

  View details for DOI 10.1155/2010/942124

  View details for PubMedID 20490262

  View details for PubMedCentralID PMC2871184

• Relationship Between Cystatin C and Coronary Artery Atherosclerosis Progression Differs by Type 1 Diabetes DIABETES TECHNOLOGY & THERAPEUTICS Maahs, D. M., Snell-Bergeon, J. K., Hokanson, J. E., Kinney, G. L., Berl, T., Rewers, M., Ogden, L. G. 2010; 12 (1): 25-33

  Abstract

  Cystatin C has been proposed to better estimate renal function and predict cardiovascular disease (CVD) than serum creatinine. To expand on our previous report, we investigated whether the relationship of cystatin C to progression of coronary artery atherosclerosis (CA) differed between individuals with type 1 diabetes (T1D) and persons without diabetes.Coronary artery calcium was measured twice over 2.4 +/- 0.4 years (n = 1,123, age = 39 +/- 9 years, 47% male, 45% T1D). Significant CA progression was defined as a > or = 2.5 increase in square root calcium volume score or development of clinical coronary artery disease. Stepwise multiple logistic regression was performed to investigate whether the association of cystatin C to CA progression differed by T1D status.The main finding and novelty of this article is that while the univariate association of cystatin C to CA progression was similar in T1D patients and persons without diabetes mellitus and in the expected direction (increased cystatin C as a biomarker of worsening renal function associated with CA progression), the association of cystatin C to progression of CA differed by T1D status (P = 0.01) after adjustment for other CVD risk factors. Unexpectedly, in persons without diabetes mellitus having relatively normal renal function, increased cystatin C was associated with decreased CA progression (odd ratio [OR] = 0.65, 95% confidence interval 0.44-0.96, P = 0.029) after adjustment, primarily due to adjustment for body mass index (BMI). Removal of BMI from this model resulted in a 49% change in the OR.Our hypothesis-generating data suggest a complex relationship among cystatin C, BMI, and CA progression that requires further study.

  View details for DOI 10.1089/dia.2009.0086

  View details for Web of Science ID 000273676100003

  View details for PubMedID 20082582

  View details for PubMedCentralID PMC2883530

• Lifestyle risk factors for atherosclerosis in adults with type 1 diabetes DIABETES & VASCULAR DISEASE RESEARCH Bishop, F. K., Maahs, D. M., Snell-Bergeon, J. K., Ogden, L. G., Kinney, G. L., Rewers, M. 2009; 6 (4): 269-275

  Abstract

  The objective of this study was to compare the amount of self-reported physical activity, alcohol and tobacco use in a large sample of adults with type 1 diabetes and non-diabetic subjects. A second aim is to test the hypothesis that these lifestyle risk factors are associated cross-sectionally with coronary artery calcification. In 2000-2002, the Coronary Artery Calcification in Type 1 Diabetes (CACTI) study applied validated questionnaires for smoking, alcohol and physical activity to 582 type 1 diabetes subjects and 724 non-diabetic subjects. More type 1 diabetes subjects reported current smoking than non-diabetic subjects (12.3% versus 8.6%, p=0.027). Overall, reported physical activity did not differ by diabetes status (p=0.79). More type 1 diabetes subjects reported never having consumed alcohol (10% versus 4%, p<0.0001) and those who drank consumed less alcohol (p=0.0015) than non-diabetic subjects. Physical activity and smoking were significantly associated with the presence of coronary artery calcification (adjusted OR=0.9, 95% CI: 0.8-0.996, p=0.045, and OR=1.7, CI: 1.1-2.6, p=0.03, respectively). Type 1 diabetes was independently associated with increased odds of coronary artery calcification (OR=3.5, 95% CI: 2.5-5.0, p<0.0001). Differences exist in lifestyle-related cardiovascular risk factors in men and women with type 1 diabetes compared with non-diabetic subjects in the CACTI study.

  View details for DOI 10.1177/1479164109346359

  View details for Web of Science ID 000270851400008

  View details for PubMedID 20368221

• The Association between Adiponectin/Leptin Ratio and Diabetes Type: The SEARCH for Diabetes in Youth Study JOURNAL OF PEDIATRICS Maahs, D. M., Hamman, R. F., D'Agostino, R., Dolan, L. M., Imperatore, G., Lawrence, J. M., Marcovina, S. M., Mayer-Davis, E. J., Pihoker, C., Dabelea, D. 2009; 155 (1): 133-135

  Abstract

  We tested the association of adiponectin/leptin ratio with diabetes type after adjusting for multiple factors in 1156 youths with newly diagnosed diabetes in the SEARCH study. Although adiponectin/leptin ratio is associated with diabetes type in youth, it is due to differences in adiponectin, but not leptin levels.

  View details for DOI 10.1016/j.jpeds.2008.12.048

  View details for Web of Science ID 000267672600033

  View details for PubMedID 19559298

  View details for PubMedCentralID PMC2743881

• Adults with type 1 diabetes eat a high-fat atherogenic diet that is associated with coronary artery calcium DIABETOLOGIA Snell-Bergeon, J. K., Chartier-Logan, C., Maahs, D. M., Ogden, L. G., Hokanson, J. E., Kinney, G. L., Eckel, R. H., Ehrlich, J., Rewers, M. 2009; 52 (5): 801-809

  Abstract

  Coronary heart disease is the leading cause of mortality among people with type 1 diabetes. Diet is an important lifestyle factor that relates to risk of CHD. The aim of this study was to examine how diet and adherence to dietary guidelines differ between adults with and without type 1 diabetes, and their correlation with CHD risk factors and coronary artery calcium (CAC).The study involved 571 people with type 1 diabetes and 696 controls, aged 19 to 56 years, who were asymptomatic for CHD. CAC was measured by electron-beam computed tomography.Compared with the controls, adults with type 1 diabetes reported a diet higher in fat, saturated fat and protein but lower in carbohydrates. Fewer than half of those with type 1 diabetes met dietary guidelines for fat and carbohydrate intake, and only 16% restricted saturated fat to less than 10% of daily energy intake. Adults with type 1 diabetes were significantly less likely to meet dietary guidelines than controls. Fat and saturated fat intakes were positively correlated, but carbohydrate intake was negatively correlated with CHD risk factors and HbA(1c). A high-fat diet and higher intake of protein were associated with greater odds of CAC, while higher carbohydrate intake was associated with reduced odds of CAC.Adults with type 1 diabetes reported consuming higher than recommended levels of fat and saturated fat. High fat intake was associated with increased CHD risk factors, worse glycaemic control and CAC. An atherogenic diet may contribute to the risk of CHD in adults with type 1 diabetes.

  View details for DOI 10.1007/s00125-009-1280-4

  View details for Web of Science ID 000264884100010

  View details for PubMedID 19219420

  View details for PubMedCentralID PMC2896567

• Prevalence and Correlates of Depression in Individuals With and Without Type 1 Diabetes DIABETES CARE Gendelman, N., Snell-Bergeon, J. K., McFann, K., Kinney, G., Wadwa, R. P., Bishop, F., Rewers, M., Maahs, D. M. 2009; 32 (4): 575-579

  Abstract

  Depression is associated with poor glycemic control and complications in people with type 1 diabetes. We assessed the prevalence of depression and antidepressant medication use among adults with and without type 1 diabetes and the association between depression and diabetes complications.In 2006-2008, the Coronary Artery Calcification in Type 1 Diabetes Study applied the Beck Depression Inventory II (BDI-II) to 458 participants with type 1 diabetes (47% male, aged 44 +/- 9 years, type 1 diabetes duration 29 +/- 9 years) and 546 participants without diabetes (nondiabetic group) (51% male, aged 47 +/- 9 years). Use of antidepressant medication was self-reported. Depression was defined as a BDI-II score >14 and/or use of antidepressant medication. Occurrence of diabetes complications (retinopathy, blindness, neuropathy, diabetes-related amputation, and kidney or pancreas transplantation) was self-reported.Mean BDI-II score, adjusted for age and sex, was significantly higher in participants with type 1 diabetes than in nondiabetic participants (least-squares mean +/- SE: 7.4 +/- 0.3 vs. 5.0 +/- 0.3; P < 0.0001). Type 1 diabetic participants reported using more antidepressant medications (20.7 vs. 12.1%, P = 0.0003). More type 1 diabetic than nondiabetic participants were classified as depressed by BDI-II cut score (17.5 vs. 5.7%, P < 0.0001) or by either BDI-II cut score or antidepressant use (32.1 vs. 16.0%, P < 0.0001). Participants reporting diabetes complications (n = 209) had higher mean BDI-II scores than those without complications (10.7 +/- 9.3 vs. 6.4 +/- 6.3, P < 0.0001).Compared with nondiabetic participants, adults with type 1 diabetes report more symptoms of depression and more antidepressant medication usage. Depression is highly prevalent in type 1 diabetes and requires further study on assessment and treatment.

  View details for DOI 10.2337/dc08-1835

  View details for Web of Science ID 000264819800009

  View details for PubMedID 19171719

  View details for PubMedCentralID PMC2660458

• Evaluation of Urinary Biomarkers for Coronary Artery Disease, Diabetes, and Diabetic Kidney Disease DIABETES TECHNOLOGY & THERAPEUTICS Snell-Bergeon, J. K., Maahs, D. M., Ogden, L. G., Kinney, G. L., Hokanson, J. E., Schiffer, E., Rewers, M., Mischak, H. 2009; 11 (1): 1-9

  Abstract

  In this study we sought to validate urinary biomarkers for diabetes and two common complications, coronary artery disease (CAD) and diabetic nephropathy (DN).A CAD score calculated by summing the product of a classification coefficient and signal amplitude of 15 urinary polypeptides was previously developed. Five sequences of biomarkers in the panel were identified as fragments of collagen alpha-1(I) and alpha-1(III). Prospectively collected urine samples available for analysis from 19 out of 20 individuals with CAD (15 with type 1 diabetes [T1D] and four without diabetes) and age-, sex-, and diabetes-matched controls enrolled in the Coronary Artery Calcification in Type 1 Diabetes study were analyzed for the CAD score using capillary electrophoresis and electrospray ionization mass spectrometry. Two panels of biomarkers that were previously defined to distinguish diabetes status were analyzed to determine their relationship to T1D. Three biomarker panels developed to distinguish DN (DNS) and two biomarker panels developed to distinguish renal disease (RDS) were examined to determine their relationship with renal function.The CAD score was associated with CAD (odds ratio with 95% confidence interval, 2.2 [1.3-5.2]; P = 0.0016) and remained significant when adjusted individually for age, albumin excretion rate (AER), blood pressure, waist circumference, intraabdominal fat, glycosylated hemoglobin, and lipids. DNS and RDS were significantly correlated with AER, cystatin C, and serum creatinine. The biomarker panels for diabetes were both significantly associated with T1D status (P < 0.05 for both).We validated a urinary proteome pattern associated with CAD and urinary proteome patterns associated with T1D and DN.

  View details for DOI 10.1089/dia.2008.0040

  View details for Web of Science ID 000262587100001

  View details for PubMedID 19132849

  View details for PubMedCentralID PMC2939844

• Birth weight [corrected] and elevated albumin to creatinine ratio in youth with diabetes: the SEARCH for Diabetes in Youth study. Pediatric nephrology Maahs, D. M., Snively, B. M., Beyer, J., Imperatore, G., Bell, R., Mayer-Davis, E. J., Dolan, L. M., Pettitt, D. J., Hirsch, I., Rodriguez, B., Dabelea, D. 2008; 23 (12): 2255-2260

  Abstract

  Low birth weight (BWT) may contribute to kidney disease and could explain some of the variance in the development of early diabetic kidney disease. This hypothesis was tested in the multicenter SEARCH study (3,714 youth with diabetes <20 years of age). A morning spot urine sample, laboratory and anthropometric data, and a medical history were obtained. Elevated albumin to creatinine ratio (ACR) was defined as > or =30 mcg albumin/mg creatinine, and BWT was categorized as low (<2,500 g), reference (2,500-4,000 g), or high (>4,000 g). The relationship of BWT to elevated ACR was analyzed using multiple logistic regression. In youth with diabetes, the prevalence of elevated ACR was 12.6% in those with low BWT, 9.7% in those with reference BWT, and 8.9% in those with high BWT. BWT category was not significantly associated with elevated ACR (p = 0.23). Those with diabetes duration >18 months (2,032) had the following association of BWT category with elevated ACR [odds ratio (OR) = 1.64, 95% confidence interval (CI) 1.00-2.69, p = 0.0503] for low BWT compared with reference BWT. Whereas low BWT may be a factor in kidney disease, little evidence was found of a relationship between low BWT and elevated ACR in this study population of youth with diabetes.

  View details for DOI 10.1007/s00467-008-0921-z

  View details for PubMedID 18607639

• Weight and elevated albumin to creatinine ratio in youth with diabetes: the SEARCH for Diabetes in Youth study PEDIATRIC NEPHROLOGY Maahs, D. M., Snively, B. M., Beyer, J., Imperatore, G., Bell, R., Mayer-Davis, E. J., Dolan, L. M., Pettitt, D. J., Hirsch, I., Rodriguez, B., Dabelea, D. 2008; 23 (12): 2255-2260

  View details for DOI 10.1007/s00467-008-0921-z

  View details for Web of Science ID 000260542400021

• Dyslipidemia in Youth with Diabetes: To Treat or Not to Treat? JOURNAL OF PEDIATRICS Maahs, D. M., Wadwa, R. P., Bishop, F., Daniels, S. R., Rewers, M., Klingensmith, G. J. 2008; 153 (4): 458-465

  View details for DOI 10.1016/j.jpeds.2008.05.062

  View details for Web of Science ID 000260101600006

  View details for PubMedID 18847618

  View details for PubMedCentralID PMC2585025

• The urinary proteome in diabetes and diabetes-associated complications: New ways to assess disease progression and evaluate therapy PROTEOMICS CLINICAL APPLICATIONS Rossing, K., Mischak, H., Rossing, P., Schanstra, J. P., Wiseman, A., Maahs, D. M. 2008; 2 (7-8): 997-1007

  Abstract

  Diabetes represents one of the main chronic diseases worldwide. Diabetes and its associated complications may be detectable even at early stages in the urinary proteome. In this article we review the current literature on urinary proteomics applied to the study of diabetes and diabetic complications. Further, we present recent data that strongly indicate urinary proteome analysis may be a valuable tool in detecting diabetes-associated pathophysiological changes at an early stage, and also may enable assessment of disease progression and efficacy of therapy. Current data indicate that collagen-derived peptides represent one of the main peptidic components in urine, which are consistently found at reduced levels in diabetes. It is tempting to speculate that this decrease in urinary collagen-derived peptides is related to an increase in extracellular matrix deposition which is a major complication in diabetes. Therefore, urinary proteome analysis might enable noninvasive assessment of this process at an early stage via determination of specific collagen fragments. This may open an avenue towards targeted therapeutic intervention.

  View details for DOI 10.1002/prca.200780166

  View details for Web of Science ID 000258088600007

  View details for PubMedID 21136900

• Determinants of adiponectin levels in young people with Type 1 diabetes DIABETIC MEDICINE Barnes, M. M., Curran-Everett, D., Hamman, R. F., Maahs, D., Mayer-Davis, E. J., D'Agostin, R. B., West, N., Dabelea, D. 2008; 25 (3): 365-369

  Abstract

  To determine whether adiponectin levels are higher in youth with Type 1 diabetes than in non-diabetic controls, and explore potential determinants for this difference.Data are from the SEARCH for Diabetes in Youth Case-Control Study. A total of 440 youth with Type 1 diabetes and 191 non-diabetic healthy controls age 10-22 years of non-Hispanic White (NHW), African-American (AA) and Hispanic (H) origin were included in this analysis. Mean adiponectin levels were compared between persons with diabetes and controls within each racial/ethnic group, sequentially adjusting for the following variables: demographic (age, sex, Tanner stage), kidney function (albumin: creatinin ratio: ACR), obesity (body mass index: BMI; waist circumference), behavioral (percent calories from fat, physical activity), and glucose control (hemoglobin A1c: HbA(1c)).Mean adiponectin levels, adjusted for age, sex and Tanner stage, were higher in persons with Type 1 diabetes than in control subjects, among NHW (17.6 vs 13.0 microg/ml, P < 0.001) and H (17.2 vs 13.0, P = 0.01), and slightly higher but not significantly so among AA (14.5 vs 12.6, P = 0.1). The differences persisted after additionally adjusting for differences in ACR, BMI and waist circumference. We found a positive relationship between adiponectin and HbA(1c) in youth with Type 1 diabetes, even after adjustment for age, sex and race/ethnicity.Adiponectin is higher in an ethnically diverse group of youth with Type 1 diabetes than in control subjects. The relationship between glycemic control and adiponectin in Type 1 diabetes requires further exploration.

  View details for DOI 10.1111/j.1464-5491.2007.02374.x

  View details for Web of Science ID 000253609300019

  View details for PubMedID 18307464

• A pediatric perspective: Adult problems in kids, new challenges in pediatric diabetes PEDIATRIC DIABETES Maahs, D. M., Daniels, S. R. 2007; 8 (6): 349-351

  View details for Web of Science ID 000252574000001

  View details for PubMedID 18036058

• Serum cystatin C predicts progression of subclinical coronary atherosclerosis in individuals with type 1 diabetes DIABETES Maahs, D. M., Ogden, L. G., Kretowski, A., Snell-Bergeon, J. K., Kinney, G. L., Berl, T., Rewers, M. 2007; 56 (11): 2774-2779

  Abstract

  Renal function is an important determinant of coronary atherosclerosis, and serum cystatin C is a novel accurate measure of glomerular filtration rate (GFR) and a predictor of cardiovascular events and mortality. We hypothesized that in individuals with type 1 diabetes, cystatin C would 1) predict progression of subclinical coronary atherosclerosis (SCA) and 2) be a stronger predictor of SCA than serum creatinine, GFR (estimated by the Cockcroft-Gault [GFRCG] and Modification of Diet in Renal Disease [GFRMDRD] formulas), and albumin excretion rate.Coronary artery calcification was measured twice, using Imatron C-150 Ultrafast CT, over a 2.5 +/- 0.4-year interval in 509 adults with type 1 diabetes (42% male, age 36 +/- 9 years, duration 23 +/- 9 years). SCA progression (n = 131) was defined as a >2.5 increase in square root calcium volume score or development of clinical coronary artery disease. Predictors of SCA progression were examined in a model selected by stepwise logistic regression and an a priori-determined model. Next, each measure of renal function was inserted into the stepwise model, one at a time, and Akaike information criterion was used to compare the fit of the competing models.The stepwise model included cystatin C (odds ratio 1.44, 95% CI 1.00-2.18, P = 0.048), age, baseline coronary artery calcification, sex, diabetes duration, systolic blood pressure, and HDL. The stepwise model had a better fit than any of the competing models with serum creatinine, GFRCG, GFRMDRD, or albumin excretion rate replacing cystatin C.In individuals with type 1 diabetes, cystatin C modestly predicts SCA.

  View details for DOI 10.2337/db07-0539

  View details for Web of Science ID 000250615900018

  View details for PubMedID 17660266

• Higher prevalence of elevated albumin excretion in youth with type 2 than type I diabetes DIABETES CARE Maahs, D. M., Snively, B. M., Bell, R. A., Dolan, L., Hirsch, I., Imperatore, G., Linder, B., Marcovina, S. M., Mayer-Davis, E. J., Pettitt, D. J., Rodriguez, B. L., Dabelea, D. 2007; 30 (10): 2593-2598

  Abstract

  To estimate the prevalence of an elevated albumin-to-creatinine ratio (ACR) (> or = 30 microg/mg) among youth with type 1 or type 2 diabetes and to identify factors associated with elevated ACR and their effect on the relationship between elevated ACR and type of diabetes.Cross-sectional data were analyzed from 3,259 participants with onset of diabetes at < 20 years of age in the SEARCH for Diabetes in Youth, a multicenter observational study of diabetes in youth. Multiple logistic regression was used to explore determinants of elevated ACR and factors accounting for differences in this prevalence between type 2 and type 1 diabetes.The prevalence of elevated ACR was 9.2% in type 1 and 22.2% in type 2 diabetes (prevalence ratio 2.4 [95% CI 1.9-3.0]; P < 0.0001). In multiple logistic regression analysis, female sex, A1C and triglyceride values, hypertension, and type of diabetes (type 2 versus type 1) were significantly associated with elevated ACR. Adjustment for variables related to insulin resistance (obesity, hypertension, dyslipidemia, and inflammation) attenuated, but did not completely explain, the association of diabetes type with elevated ACR.Youth with type 2 diabetes have a higher prevalence of elevated ACR than youth with type 1 diabetes, in an association that apparently does not completely depend on age, duration of diabetes, race/ethnicity, sex, level of glycemic control, or features of insulin resistance.

  View details for DOI 10.2337/dc07-0450

  View details for Web of Science ID 000250223400036

  View details for PubMedID 17630264

• Determinants of serum adiponectin in persons with and without type 1 diabetes AMERICAN JOURNAL OF EPIDEMIOLOGY Maahs, D. M., Ogden, L. G., Snell-Bergeon, J. K., Kinney, G. L., Wadwal, R. P., Hokanson, J. E., Dabelea, D., Kretowskil, A., Eckel, R. H., Rewers, M. 2007; 166 (6): 731-740

  Abstract

  Low levels of adiponectin have been related to coronary heart disease, but adiponectin is higher in persons with type 1 diabetes who have an increased rate of coronary disease. In the Coronary Artery Calcification in Type 1 Diabetes Study (2000-2002), the authors investigated potential determinants of elevated adiponectin levels in persons with type 1 diabetes and whether a difference exists compared with nondiabetic persons. Serum adiponectin was measured in 1,393 persons (sex: 48% male; age: 38 (standard deviation: 9) years; diabetes duration: 23 (standard deviation: 9) years; 54% nondiabetic and 46% with type 1 diabetes). Determinants of log-transformed adiponectin levels were evaluated by multiple linear regression analysis with interaction terms to determine whether predictors of adiponectin levels differed by diabetes status. Adiponectin levels were higher in type 1 diabetic than nondiabetic persons (13.5 (standard deviation: 1.0) vs. 8.8 (standard deviation: 1.0) microg/ml; p < 0.0001), adjusting for age, gender, body mass index, and glomerular filtration rate. The final regression model explained 67% of the difference in adiponectin levels between type 1 diabetic and nondiabetic persons. The variables explaining this difference included high density lipoprotein cholesterol, albumin excretion rate, plasminogen activator inhibitor-1, and hemoglobin A1c level. Adiponectin is higher in type 1 diabetic than nondiabetic persons. Although some of the difference can be explained, further study is needed to better understand the relation between elevated adiponectin levels and patient outcomes, including coronary heart disease.

  View details for DOI 10.1093/aje/kwm125

  View details for Web of Science ID 000249328600014

  View details for PubMedID 17591595

• ACE-I/ARB treatment in type 1 diabetes patients with albuminuria is associated with lower odds of progression of coronary artery calcification JOURNAL OF DIABETES AND ITS COMPLICATIONS Maahs, D. M., Snell-Bergeon, J. K., Kinney, G. L., Wadwa, R. P., Garg, S., Ogden, L. G., Rewers, M. 2007; 21 (5): 273-279

  Abstract

  The objective of this study was to determine whether baseline albuminuria predicts coronary artery calcification (CAC) progression in subjects with type 1 diabetes and whether angiotensin-converting enzyme inhibitor (ACE-I) or angiotensin II type I receptor blocker (ARB) treatment is associated with lower odds of CAC progression.In 2000-2002, the Coronary Artery Calcification in Type 1 Diabetes study enrolled 652 subjects with type 1 diabetes who were between 19 and 56 years old and had no known history of coronary artery disease (CAD). In this analysis, CAC progression over 2.5+/-0.4 years was evaluated in 478 subjects (age=37+/-9 years; male=45%; diabetes duration=23+/-9 years) at a follow-up visit. Albuminuria was defined by American Diabetes Association criteria, and microalbuminuria and macroalbuminuria were combined for the analysis. Logistic regression was used to evaluate the relationship between baseline categorical presence of albuminuria and CAC progression.At baseline, of the 478 subjects, 157 (33%) were on ACE-I/ARB treatment and 83 (17%) had albuminuria, with 114 (24%) having CAC progression at follow-up. In backward logistic regression, presence of albuminuria at baseline predicted progression of CAC among subjects not treated with ACE-I/ARB [odds ratio=4.06; 95% confidence interval (CI)=1.45-11.35; P=.008]. Among the subjects with albuminuria, the odds of progression was 62% lower (95% CI=88% decrease to 23% increase; P=.106) in those treated with ACE-I/ARB.Albuminuria is a significant independent risk factor for CAC progression in young type 1 diabetes patients asymptomatic for CAD, and ACE-I/ARB treatment is associated with substantially lower odds of CAC progression.

  View details for DOI 10.1016/j.jdiacomp.2006.04.004

  View details for Web of Science ID 000249622500001

  View details for PubMedID 17825750

• Polymorphisms of the renin-angiotensin system genes predict progression of subclinical coronary atherosclerosis DIABETES Kretowski, A., McFann, K., Hokanson, J. E., Maahs, D., Kinney, G., Snell-Bergeon, J. K., Wadwa, R. P., Eckel, R. H., Ogden, L., Garg, S., Li, J., Cheng, S., Erlich, H. A., Rewers, M. 2007; 56 (3): 863-871

  Abstract

  Premature coronary artery disease (CAD) in subjects with type 1 diabetes dramatically affects quality of life and morbidity and leads to premature death, but there is still little known about the mechanisms and predictors of this complication. In the present study, we explored the role of genetic variants of angiotensinogen (AGT, M235T), ACE (I/D), and angiotensin type 1 receptor (ATR1, A1166C) as predictors of rapid progression of subclinical coronary atherosclerosis. Five-hundred eighty-five type 1 diabetic patients and 592 similar age and sex control subjects were evaluated for progression of coronary artery calcification (CAC), a marker of subclinical CAD, before and after a 2.5-year follow-up. In logistic regression analysis, CAC progression was dramatically more likely in type 1 diabetic subjects not treated with ACE inhibitor/angiotensin receptor blocker who had the TT-ID-AA/AC genotype combination than in those with other genotypes (odds ratio 11.6 [95%CI 4.5-29.6], P < 0.0001) and was even stronger when adjusted for cardiovascular disease risk factors and the mean A1C (37.5 [3.6-388], P = 0.002). In conclusion, a combination of genotype variants of the renin-angiotensin system genes is a powerful determinant of subclinical progression of coronary artery atherosclerosis in type 1 diabetic patients and may partially explain accelerated CAD in type 1 diabetes.

  View details for DOI 10.2337/db06-1321

  View details for Web of Science ID 000244827500037

  View details for PubMedID 17327458

• Longitudinal lipid screening and use of lipid-lowering medications in pediatric type 1 diabetes JOURNAL OF PEDIATRICS Maahs, D. M., Wadwa, R. P., McFann, K., Nadeau, K., Williams, M. R., Eckel, R. H., Klingensmith, G. J. 2007; 150 (2): 146-150

  Abstract

  Because cardiovascular disease (CVD) is the leading cause of death in patients with type 1 diabetes (T1D) and dyslipidemia is an important CVD risk factor, we investigated dyslipidemia and its treatment in children with T1D.Subjects had T1D (n = 360), repeated lipid measurements (n = 1095; mean, 3.04 +/- 0.94; range, 2 to 11), and were seen between 1994 and 2004. Total cholesterol (TC), high-density lipoprotein cholesterol (HDL), and non-HDL cholesterol (non-HDL) were categorized on the basis of published guidelines. Age, diabetes duration, sex, body mass index, HbA1c, and lipid-lowering medication use were recorded. Predictors of TC, HDL, and non-HDL were determined.Sustained abnormalities existed for TC > or = 200 mg/dL (16.9%); HDL < 35 mg/dL (3.3%); and non-HDL > or = 130 mg/dL (27.8%), > or = 160 mg/dL (10.6%), and > or = 190 mg/dL (3.3%). Lipid-lowering medications were started on 23 patients. In mixed model longitudinal data analyses, HbA1c was significantly related to TC and non-HDL. Body mass index z-score was inversely related to HDL.In this retrospective, longitudinal study of pediatric patients with T1D with repeated lipid measurements, sustained abnormal levels for TC, HDL, and non-HDL were present. Prospective longitudinal data for dyslipidemia in youth with T1D are needed.

  View details for DOI 10.1016/j.jpeds.2006.10.054

  View details for Web of Science ID 000244111300009

  View details for PubMedID 17236891

• Editorial: Mortality and renal disease in type 1 diabetes mellitus- Progress made, more to be done JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM Maahs, D. M., Rewers, M. 2006; 91 (10): 3757-3759

  View details for DOI 10.1210/jc.2006-1730

  View details for Web of Science ID 000241100900008

  View details for PubMedID 17028289

• The apolipoprotein A-IV Gln360His polymorphism predicts progression of coronary artery calcification in patients with type 1 diabetes DIABETOLOGIA Kretowski, A., Hokanson, J. E., McFann, K., Kinney, G. L., Snell-Bergeon, J. K., Maahs, D. M., Wadwa, R. P., Eckel, R. H., Ogden, L. G., Garg, S. K., Cheng, J. L., Erlich, H. A., Rewers, M. 2006; 49 (8): 1946-1954

  Abstract

  Individuals with type 1 diabetes have an increased incidence of coronary artery disease (CAD) and a higher risk of cardiovascular death compared with individuals of the same age in the general population. While chronic hyperglycaemia and insulin resistance partially explain excess CAD, little is known about the potential genetic determinants of accelerated coronary atherosclerosis in type 1 diabetes. The aim of the present study was to evaluate the association of apolipoprotein A-IV (APOA4) polymorphisms with coronary artery calcification (CAC) progression, a marker of subclinical atherosclerosis.Two previously well-studied functional APOA4 polymorphisms resulting in the substitution of the amino acid Thr for Ser at codon 347 and Gln for His at codon 360 were genotyped in 634 subjects with type 1 diabetes and 739 non-diabetic control subjects, the participants of the prospective Coronary Artery Calcification in Type 1 Diabetes (CACTI) study.The His360 allele was associated with a significantly higher risk of CAC progression among patients with type 1 diabetes (33.7 vs 21.2%, p=0.014), but not in the control subjects (14.1 vs 11.1%, p=0.42). Logistic regression analysis confirmed that the presence of the APOA4 His360 allele predicts an increased risk of progression of coronary atherosclerosis in adults with type 1 diabetes of long duration (odds ratio = 3.3, p=0.003 after adjustment for covariates associated with CAD risk). CONCLUSIONS /INTERPRETATION: This is the first report suggesting an association between the APOA4 Gln360His polymorphism and risk of CAC progression in subjects with type 1 diabetes. Additional studies are needed to explore potential interactions between APOA4 genotypes and metabolic/oxidative stress components of the diabetic milieu leading to rapid progression of atherosclerosis.

  View details for DOI 10.1007/s00125-006-0317-1

  View details for Web of Science ID 000238859900028

  View details for PubMedID 16770585

• Assessing weight-related quality of life in adolescents OBESITY Kolotkin, R. L., Zeller, M., Modi, A. C., Samsa, G. P., Quinlan, N. P., Yanovski, J. A., Bell, S. K., Maahs, D. M., de Serna, D. G., Roehrig, H. R. 2006; 14 (3): 448-457

  Abstract

  The development of a new weight-related measure to assess quality of life in adolescents [Impact of Weight on Quality of Life (IWQOL)-Kids] is described.Using a literature search, clinical experience, and consultation with pediatric clinicians, 73 items were developed, pilot tested, and administered to 642 participants, 11 to 19 years old, recruited from weight loss programs/studies and community samples (mean z-BMI, 1.5; range, -1.2 to 3.4; mean age, 14.0; 60% female; 56% white). Participants completed the 73 items and the Pediatric Quality of Life Inventory and were weighed and measured.Four factors (27 items) were identified (physical comfort, body esteem, social life, and family relations), accounting for 71% of the variance. The IWQOL-Kids demonstrated excellent psychometric properties. Internal consistency coefficients ranged from 0.88 to 0.95 for scales and equaled 0.96 for total score. Convergent validity was demonstrated with strong correlations between IWQOL-Kids total score and the Pediatric Quality of Life Inventory (r = 0.76, p < 0.0001). Significant differences were found across BMI groups and between clinical and community samples, supporting the sensitivity of this measure. Participants in a weight loss camp demonstrated improved IWQOL-Kids scores, suggesting responsiveness of the IWQOL-Kids to weight loss/social support intervention.The present study provides preliminary evidence regarding the psychometric properties of the IWQOL-Kids, a weight-related quality of life measure for adolescents. Given the rise of obesity in youth, the development of a reliable and valid weight-related measure of quality of life is timely.

  View details for Web of Science ID 000250566800015

  View details for PubMedID 16648616

  View details for PubMedCentralID PMC2374918

• Soluble interleukin-2 receptor as a marker for progression of coronary artery calcification in type 1 diabetes INTERNATIONAL JOURNAL OF BIOCHEMISTRY & CELL BIOLOGY Wadwa, R. P., Kinney, G. L., Ogden, L., Snell-Bergeon, J. K., Maahs, D. M., Cornell, E., Tracy, R. P., Rewers, M. 2006; 38 (5-6): 996-1003

  Abstract

  Soluble interleukin-2 receptor (sIL2r), a marker of T cell activation, is elevated in inflammatory processes, such as rheumatoid arthritis, hepatitis and neoplasm. We explored a potential association between plasma sIL2r levels and progression of coronary artery calcification (CAC), a marker for subclinical atherosclerosis, in a prospectively followed cohort of type 1 diabetic and non-diabetic subjects, aged 20-59 years, with no history of coronary artery disease.CAC progression was assessed by electron beam tomography over 2.6 years (range 1.6-3.2). Plasma sIL2r levels were measured in a nested case-control substudy of 98 subjects (67 diabetic, 31 non-diabetic) with and 173 subjects (84 diabetic, 89 non-diabetic) without significant CAC progression. Log-transformed sIL2r levels were analyzed by conditional logistic regression to compare subjects with and without significant CAC progression.SIL2r was a significant predictor for CAC progression after adjusting for presence of baseline CAC, age, gender, diabetes status, baseline calcium volume score and adiponectin (OR 1.99, 95% CI 1.09-3.61, p = 0.02 for a doubling of sIL2r level). Addition of BMI, LDL, HDL, hypertension, smoking status, HbA1c, CRP, fibrinogen, homocysteine and PAI-1 to regression models weakened but did not remove sIL2r as a predictor of CAC progression. There was no indication that this effect was different by diabetes status (p = 0.6 for diabetes-sIL2r interaction).Elevated plasma sIL2r is associated with CAC progression independent of traditional coronary artery disease risk factors in type 1 diabetic and non-diabetic young adults. SIL2r should be considered as a novel marker of inflammation leading to coronary artery disease.

  View details for DOI 10.1016/j.biocel.2005.09.015

  View details for Web of Science ID 000236525800029

  View details for PubMedID 16271309

• Randomized, double-blind, placebo-controlled trial of orlistat for weight loss in adolescents. Endocrine practice Maahs, D., De Serna, D. G., Kolotkin, R. L., Ralston, S., Sandate, J., Qualls, C., Schade, D. S. 2006; 12 (1): 18-28

  Abstract

  To evaluate the efficacy of orlistat to enhance weight loss in obese adolescents.The study was a 6-month randomized, double-blind, placebo-controlled trial to compare the effects of orlistat (120 mg orally 3 times a day) and placebo on reduction of body mass index (BMI). Forty adolescents between 14 and 18 years of age with a mean BMI of 40 kg/m2 entered the protocol between December 2002 and February 2003. Study subjects stayed overnight in the General Clinical Research Center, during which dietary records were reviewed and lifestyle recommendations were given. The study participants received either orlistat (120 mg orally 3 times a day) or placebo and were assessed monthly for 6 months. At 0, 3, and 6 months, fasting laboratory tests were performed. The primary end point was the change in BMI from baseline to 6 months. Secondary outcomes included changes in weight, lean body mass, and results of blood chemistry studies.No statistically significant difference was noted between the 2 study groups for decrease in BMI from baseline to 6 months (P = 0.39). The decrease in BMI within the orlistat group (-1.3 +/- 1.6 kg/m2; P = 0.04) and within the placebo group (-0.8 +/- 3.0 kg/m2; P = 0.02), however, was statistically significant. Laboratory measurements did not differ between the 2 groups. In comparison with the placebo group, the orlistat group had increased adverse events, primarily gastrointestinal symptoms and findings.In this study of obese adolescents, orlistat did not significantly reduce BMI in comparison with placebo at 6 months.

  View details for PubMedID 16524859

• Total cholesterol and high-density lipoprotein levels in pediatric subjects with type 1 diabetes mellitus JOURNAL OF PEDIATRICS Maahs, D. M., Maniatis, A. K., Nadeau, K., Wadwa, R. P., McFann, K., Klingensmith, G. J. 2005; 147 (4): 544-546

  Abstract

  This study reports serum lipid levels in 682 children with type 1 diabetes mellitus. We found that 3.5% of the subjects had a high-density lipoprotein (HDL) cholesterol level < 35 mg/dL, 15.4% had a total cholesterol (TC) level>200 mg/dL, and 18.6% were abnormal for either HDL or TC, compared with prevalences of 5.7%, 11.2%, and 16.3%, respectively, reported in the National Health and Nutrition Examination Survey 2001-02. Hemoglobin A1c value was significantly related to TC and non-HDL cholesterol levels.

  View details for DOI 10.1016/j.jpeds.2005.04.068

  View details for Web of Science ID 000232865300028

  View details for PubMedID 16227045

• Awareness and treatment of dyslipidemia in young adults with type 1 diabetes DIABETES CARE Wadwa, R. P., Kinney, G. L., Maahs, D. M., Snell-Bergeon, J., Hokanson, J. E., Garg, S. K., Eckel, R. H., Rewers, M. 2005; 28 (5): 1051-1056

  Abstract

  Dyslipidemia is a preventable major risk factor for coronary heart disease (CHD). Despite an increased risk of CHD in type 1 diabetes, little is known concerning awareness and adequacy of dyslipidemia treatment in this population. In this report, we describe the prevalence of dyslipidemia and adequacy of pharmacological treatment in patients with type 1 diabetes and comparable nondiabetic subjects.From 2000 to 2002, the Coronary Artery Calcification in Type 1 Diabetes study obtained fasting lipid profiles in 1,416 individuals aged 19-56 years with no history of CHD: 652 type 1 diabetic patients (46% men, mean age 37 +/- 9 years) and 764 nondiabetic control subjects (50% men, mean age 39 +/- 9 years). These data combined with patient questionnaire results were used to determine prevalence of dyslipidemia and adequacy of pharmacological treatment. For all subjects, dyslipidemia was defined using National Cholesterol Education Program Adult Treatment Panel III criteria.Type 1 diabetic subjects had significantly less dyslipidemia than nondiabetic control subjects (47 vs. 58%, P < 0.001), and a higher percentage of those with abnormal lipids were aware of (52 vs. 34%, P < 0.0001), on medication for (36 vs. 9%, P < 0.0001), and in control of their lipid levels (15 vs. 1.4%, P < 0.001). Of those on treatment, control was achieved in 41% of type 1 diabetic subjects and 15% of nondiabetic participants (P < 0.01).Dyslipidemia, a major risk factor for CHD, remains largely undiagnosed and undertreated in high-risk populations, such as patients with type 1 diabetes.

  View details for Web of Science ID 000228701100011

  View details for PubMedID 15855566

• Low plasma adiponectin levels predict progression of coronary artery calcification CIRCULATION Maahs, D. M., Ogden, L. G., Kinney, G. L., Wadwa, P., Snell-Bergeon, J. K., Dabelea, D., Hokanson, J. E., Ehrlich, J., Eckel, R. H., Rewers, M. 2005; 111 (6): 747-753

  Abstract

  Circulating adiponectin levels are lower in men than in women and lower in advanced coronary artery disease, obesity, and type 2 but not type 1 diabetes. However, it is not known whether low adiponectin levels predict development of atherosclerosis independently of other cardiovascular risk factors.Progression of coronary artery calcification (CAC) over an average of 2.6 years (range, 1.6 to 3.3) was assessed in a cohort of patients with type 1 diabetes and nondiabetic subjects 19 to 59 years of age. In this nested case-control substudy, plasma adiponectin levels were measured in 101 cases with significant CAC progression and in 205 controls. Controls were oversampled on the basis of age, gender, diabetes status, and presence of baseline CAC. In conditional logistic regression adjusted for baseline CAC volume and other significant predictors of CAC progression, adiponectin levels were inversely related to progression of CAC in diabetic (OR, 0.47; 95% CI, 0.24 to 0.94) and nondiabetic (OR, 0.15; 95% CI, 0.05 to 0.40 for a doubling in adiponectin levels) subjects. Adjustment for additional cardiovascular risk factors did not change this association. In conditional logistic regression models by quartiles of plasma adiponectin levels, the probability value for trend was statistically significant for all participants (P<0.001) and nondiabetic participants (P<0.001) and was borderline for type 1 diabetics (P=0.08).Low plasma adiponectin levels are associated with progression of CAC in type 1 diabetic and nondiabetic subjects independently of other cardiovascular risk factors.

  View details for DOI 10.1161/01.CIR.0000155251.03724.A5

  View details for Web of Science ID 000227007800007

  View details for PubMedID 15699257

• Hypertension prevalence, awareness, treatment, and control in an adult type 1 diabetes population and a comparable general population DIABETES CARE Maahs, D. M., Hokanson, J., Kinney, G. L., Ehrlich, J., Wadwa, P., Garg, S., Snell-Bergeon, J. K., Eckel, R. H., Dabelea, D., Rewers, M. J. 2005; 28 (2): 301-306

  Abstract

  To compare the prevalence, awareness, treatment, and control of hypertension in a population-representative sample of adults with type 1 diabetes and comparable nondiabetic control subjects.In 2000-2002, the Coronary Artery Calcification in Type 1 Diabetes Study enrolled 1,416 individuals aged 19-56 years with no known history of coronary artery disease: 652 type 1 diabetic patients (46% male, mean age 37 years) and 764 nondiabetic control subjects (50% male, mean age 39 years). Subjects were asked if they had been told by a physician that they had hypertension or were on a blood pressure medication. Blood pressure was measured using standardized Joint National Committee (JNC) protocol.Type 1 diabetic subjects, compared with nondiabetic subjects, had higher rates of hypertension prevalence (43 vs. 15%, P < 0.001), awareness (53 vs. 45%, P = 0.11), treatment (87 vs. 47%, P < 0.001), and control (55 vs. 32%, P < 0.001) for the JNC 6 goal (130/85 mmHg). Only 42% of all type 1 diabetic hypertensive subjects met the new JNC 7 goal (130/80 mmHg). Type 1 diabetic subjects had better blood pressure control (72 vs. 32%, P < 0.0001), using 140/90 mmHg as a common measure. The majority of treated subjects were on a single antihypertensive agent (75 vs. 64%).Subjects with type 1 diabetes have higher rates of hypertension prevalence, treatment, and control than nondiabetic subjects. However, hypertension remains largely uncontrolled, even if treated in high-risk populations, such as type 1 diabetic subjects and undiagnosed individuals in the general population. Achieving more stringent blood pressure goals will require increased attention and may necessitate the use of multiple antihypertensive agents.

  View details for Web of Science ID 000226612900011

  View details for PubMedID 15677783