Tandy Aye

All Publications

• 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

  View details for PubMedCentralID PMC5094319

• 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

• Changes in beta cell function during the proximate post-diagnosis period in persons with type 1 diabetes PEDIATRIC DIABETES Dimeglio, L. A., Cheng, P., Beck, R. W., Kollman, C., Ruedy, K. J., Slover, R., Aye, T., Weinzimer, S. A., Bremer, A. A., Buckingham, B. 2016; 17 (4): 237-243

  Abstract

  Prior studies examining beta-cell preservation in type 1 diabetes have predominantly assessed stimulated C-peptide concentrations approximately 10 wk after diagnosis. We examined whether earlier assessments might aid in prediction of beta cell function over time.Using data from a multi-center randomized trial assessing the effect of intensive diabetes management initiated within 1 wk of diagnosis, we assessed which clinical factors predicted 90-min mixed-meal tolerance test (MMTT) stimulated C-peptide values obtained 2 and 6 wk after diagnosis. We also studied associations of these factors with C-peptide values at 1- and 2-year post-diagnosis. Data from intervention and control groups were pooled.Among 67 study participants (mean age 13.3 ± 5.7 yr, range 7.8-45.7 yr) in multivariable analyses, C-peptide increased from baseline to 2 wks and then 6 wk. C-peptide levels at these times were significantly correlated with 1- and 2-yr C-peptide concentrations (all p < 0.001), with the strongest observed associations between 6-wk C-peptide and the 1- and 2-yr values (r = 0.66 and r = 0.61, respectively). In multivariable analyses, greater baseline and 6-wk C-peptide, and older age independently predicted greater 1- and 2-yr C-peptide concentrations.C-peptide assessments close to diagnosis were predictive of subsequent C-peptide production. Our data demonstrate a clear increase in C-peptide over the initial 6 wk after diabetes diagnosis followed by a plateau. Our data do not suggest that MMTT assessments performed closer to diagnosis than 6 wk would improve prediction of subsequent residual beta cell function.

  View details for DOI 10.1111/pedi.12271

  View details for Web of Science ID 000379831900001

  View details for PubMedID 25720763

• Longitudinal Evaluation of Cognitive Functioning in Young Children with Type 1 Diabetes over 18 Months. Journal of the International Neuropsychological Society Cato, M. A., Mauras, N., Mazaika, P., Kollman, C., Cheng, P., Aye, T., Ambrosino, J., Beck, R. W., Ruedy, K. J., Reiss, A. L., Tansey, M., White, N. H., Hershey, T. 2016; 22 (3): 293-302

  Abstract

  Decrements in cognitive function may already be evident in young children with type 1 diabetes (T1D). Here we report prospectively acquired cognitive results over 18 months in a large cohort of young children with and without T1D.A total of 144 children with T1D (mean HbA1c: 7.9%) and 70 age-matched healthy controls (mean age both groups 8.5 years; median diabetes duration 3.9 years; mean age of onset 4.1 years) underwent neuropsychological testing at baseline and after 18-months of follow-up. We hypothesized that group differences observed at baseline would be more pronounced after 18 months, particularly in those T1D patients with greatest exposure to glycemic extremes.Cognitive domain scores did not differ between groups at the 18 month testing session and did not change differently between groups over the follow-up period. However, within the T1D group, a history of diabetic ketoacidosis (DKA) was correlated with lower Verbal IQ and greater hyperglycemia exposure (HbA1c area under the curve) was inversely correlated to executive functions test performance. In addition, those with a history of both types of exposure performed most poorly on measures of executive function.The subtle cognitive differences between T1D children and nondiabetic controls observed at baseline were not observed 18 months later. Within the T1D group, as at baseline, relationships between cognition (Verbal IQ and executive functions) and glycemic variables (chronic hyperglycemia and DKA history) were evident. Continued longitudinal study of this T1D cohort and their carefully matched healthy comparison group is planned.

  View details for DOI 10.1017/S1355617715001289

  View details for PubMedID 26786245

  View details for PubMedCentralID PMC4856439

• Variations in Brain Volume and Growth in Young Children With Type 1 Diabetes. Diabetes Mazaika, P. K., Weinzimer, S. A., Mauras, N., Buckingham, B., White, N. H., Tsalikian, E., Hershey, T., Cato, A., Aye, T., Fox, L., Wilson, D. M., Tansey, M. J., Tamborlane, W., Peng, D., Raman, M., Marzelli, M., Reiss, A. L. 2016; 65 (2): 476-485

  Abstract

  Early-onset type 1 diabetes may affect the developing brain during a critical window of rapid brain maturation. Structural MRI was performed on 141 children with diabetes (4-10 years of age at study entry) and 69 age-matched control subjects at two time points spaced 18 months apart. For the children with diabetes, the mean (±SD) HbA1c level was 7.9 ± 0.9% (63 ± 9.8 mmol/mol) at both time points. Relative to control subjects, children with diabetes had significantly less growth of cortical gray matter volume and cortical surface area and significantly less growth of white matter volume throughout the cortex and cerebellum. For the population with diabetes, the change in the blood glucose level at the time of scan across longitudinal time points was negatively correlated with the change in gray and white matter volumes, suggesting that fluctuating glucose levels in children with diabetes may be associated with corresponding fluctuations in brain volume. In addition, measures of hyperglycemia and glycemic variation were significantly negatively correlated with the development of surface curvature. These results demonstrate that early-onset type 1 diabetes has widespread effects on the growth of gray and white matter in children whose blood glucose levels are well within the current treatment guidelines for the management of diabetes.

  View details for DOI 10.2337/db15-1242

  View details for PubMedID 26512024

  View details for PubMedCentralID PMC4747456

• 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 Web of Science ID 000356933600012

  View details for PubMedID 26049549

  View details for PubMedCentralID PMC4477332

• 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 Web of Science ID 000354168400005

  View details for PubMedID 25761202

  View details for PubMedCentralID PMC4432491

• Longitudinal Assessment of Neuroanatomical and Cognitive Differences in Young Children With Type 1 Diabetes: Association With Hyperglycemia DIABETES Mauras, N., Mazaika, P., Buckingham, B., Weinzimer, S., White, N. H., Tsalikian, E., Hershey, T., Cato, A., Cheng, P., Kollman, C., Beck, R. W., Ruedy, K., Aye, T., Fox, L., Arbelaez, A. M., Wilson, D., Tansey, M., Tamborlane, W., Peng, D., Marzelli, M., Winer, K. K., Reiss, A. L. 2015; 64 (5): 1770-1779

  Abstract

  Significant regional differences in gray and white matter volume and subtle cognitive differences between young diabetic and nondiabetic children have been observed. Here, we assessed whether these differences change over time and the relation with dysglycemia. Children ages 4 to <10 years with (n = 144) and without (n = 72) type 1 diabetes (T1D) had high-resolution structural MRI and comprehensive neurocognitive tests at baseline and 18 months and continuous glucose monitoring and HbA1c performed quarterly for 18 months. There were no differences in cognitive and executive function scores between groups at 18 months. However, children with diabetes had slower total gray and white matter growth than control subjects. Gray matter regions (left precuneus, right temporal, frontal, and parietal lobes and right medial-frontal cortex) showed lesser growth in diabetes, as did white matter areas (splenium of the corpus callosum, bilateral superior-parietal lobe, bilateral anterior forceps, and inferior-frontal fasciculus). These changes were associated with higher cumulative hyperglycemia and glucose variability but not with hypoglycemia. Young children with T1D have significant differences in total and regional gray and white matter growth in brain regions involved in complex sensorimotor processing and cognition compared with age-matched control subjects over 18 months, suggesting that chronic hyperglycemia may be detrimental to the developing brain.

  View details for DOI 10.2337/db14-1445

  View details for Web of Science ID 000353431200032

  View details for PubMedID 25488901

  View details for PubMedCentralID PMC4407847

• 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

  View details for PubMedCentralID PMC4067393

• Cognitive functioning in young children with type 1 diabetes. Journal of the International Neuropsychological Society Cato, M. A., Mauras, N., Ambrosino, J., Bondurant, A., Conrad, A. L., Kollman, C., Cheng, P., Beck, R. W., Ruedy, K. J., Aye, T., Reiss, A. L., White, N. H., Hershey, T. 2014; 20 (2): 238-247

  Abstract

  The aim of this study was to assess cognitive functioning in children with type 1 diabetes (T1D) and examine whether glycemic history influences cognitive function. Neuropsychological evaluation of 216 children (healthy controls, n = 72; T1D, n = 144) ages 4-10 years across five DirecNet sites. Cognitive domains included IQ, Executive Functions, Learning and Memory, and Processing Speed. Behavioral, mood, parental IQ data, and T1D glycemic history since diagnosis were collected. The cohorts did not differ in age, gender or parent IQ. Median T1D duration was 2.5 years and average onset age was 4 years. After covarying age, gender, and parental IQ, the IQ and the Executive Functions domain scores trended lower (both p = .02, not statistically significant adjusting for multiple comparisons) with T1D relative to controls. Children with T1D were rated by parents as having more depressive and somatic symptoms (p < .001). Learning and memory (p = .46) and processing speed (p = .25) were similar. Trends in the data supported that the degree of hyperglycemia was associated with Executive Functions, and to a lesser extent, Child IQ and Learning and Memory. Differences in cognition are subtle in young children with T1D within 2 years of onset. Longitudinal evaluations will help determine whether these findings change or become more pronounced with time. (JINS, 2014, 20, 238-247).

  View details for DOI 10.1017/S1355617713001434

  View details for PubMedID 24512675

• Alterations in white matter structure in young children with type 1 diabetes. Diabetes care Barnea-Goraly, N., Raman, M., Mazaika, P., Marzelli, M., Hershey, T., Weinzimer, S. A., Aye, T., Buckingham, B., Mauras, N., White, N. H., Fox, L. A., Tansey, M., Beck, R. W., Ruedy, K. J., Kollman, C., Cheng, P., Reiss, A. L. 2014; 37 (2): 332-340

  Abstract

  To investigate whether type 1 diabetes affects white matter (WM) structure in a large sample of young children.Children (ages 4 to <10 years) with type 1 diabetes (n = 127) and age-matched nondiabetic control subjects (n = 67) had diffusion weighted magnetic resonance imaging scans in this multisite neuroimaging study. Participants with type 1 diabetes were assessed for HbA1c history and lifetime adverse events, and glucose levels were monitored using a continuous glucose monitor (CGM) device and standardized measures of cognition.Between-group analysis showed that children with type 1 diabetes had significantly reduced axial diffusivity (AD) in widespread brain regions compared with control subjects. Within the type 1 diabetes group, earlier onset of diabetes was associated with increased radial diffusivity (RD) and longer duration was associated with reduced AD, reduced RD, and increased fractional anisotropy (FA). In addition, HbA1c values were significantly negatively associated with FA values and were positively associated with RD values in widespread brain regions. Significant associations of AD, RD, and FA were found for CGM measures of hyperglycemia and glucose variability but not for hypoglycemia. Finally, we observed a significant association between WM structure and cognitive ability in children with type 1 diabetes but not in control subjects.These results suggest vulnerability of the developing brain in young children to effects of type 1 diabetes associated with chronic hyperglycemia and glucose variability.

  View details for DOI 10.2337/dc13-1388

  View details for PubMedID 24319123

  View details for PubMedCentralID PMC3898758

• High success rates of sedation-free brain MRI scanning in young children using simple subject preparation protocols with and without a commercial mock scanner-the Diabetes Research in Children Network (DirecNet) experience. Pediatric radiology Barnea-Goraly, N., Weinzimer, S. A., Ruedy, K. J., Mauras, N., Beck, R. W., Marzelli, M. J., Mazaika, P. K., Aye, T., White, N. H., Tsalikian, E., Fox, L., Kollman, C., Cheng, P., Reiss, A. L. 2014; 44 (2): 181-186

  Abstract

  The ability to lie still in an MRI scanner is essential for obtaining usable image data. To reduce motion, young children are often sedated, adding significant cost and risk.We assessed the feasibility of using a simple and affordable behavioral desensitization program to yield high-quality brain MRI scans in sedation-free children.222 children (4-9.9 years), 147 with type 1 diabetes and 75 age-matched non-diabetic controls, participated in a multi-site study focused on effects of type 1 diabetes on the developing brain. T1-weighted and diffusion-weighted imaging (DWI) MRI scans were performed. All children underwent behavioral training and practice MRI sessions using either a commercial MRI simulator or an inexpensive mock scanner consisting of a toy tunnel, vibrating mat, and video player to simulate the sounds and feel of the MRI scanner.205 children (92.3%), mean age 7 ± 1.7 years had high-quality T1-W scans and 174 (78.4%) had high-quality diffusion-weighted scans after the first scan session. With a second scan session, success rates were 100% and 92.5% for T1-and diffusion-weighted scans, respectively. Success rates did not differ between children with type 1 diabetes and children without diabetes, or between centers using a commercial MRI scan simulator and those using the inexpensive mock scanner.Behavioral training can lead to a high success rate for obtaining high-quality T1-and diffusion-weighted brain images from a young population without sedation.

  View details for DOI 10.1007/s00247-013-2798-7

  View details for PubMedID 24096802

  View details for PubMedCentralID PMC3946760

• Alterations in white matter structure in young children with type 1 diabetes mellitus DIABETES CARE Barnea-Goraly, N., Raman, M., Mazaika, P., Marzelli, M., et al 2014: 332–40

  Abstract

  To investigate whether type 1 diabetes affects white matter (WM) structure in a large sample of young children.Children (ages 4 to <10 years) with type 1 diabetes (n = 127) and age-matched nondiabetic control subjects (n = 67) had diffusion weighted magnetic resonance imaging scans in this multisite neuroimaging study. Participants with type 1 diabetes were assessed for HbA1c history and lifetime adverse events, and glucose levels were monitored using a continuous glucose monitor (CGM) device and standardized measures of cognition.Between-group analysis showed that children with type 1 diabetes had significantly reduced axial diffusivity (AD) in widespread brain regions compared with control subjects. Within the type 1 diabetes group, earlier onset of diabetes was associated with increased radial diffusivity (RD) and longer duration was associated with reduced AD, reduced RD, and increased fractional anisotropy (FA). In addition, HbA1c values were significantly negatively associated with FA values and were positively associated with RD values in widespread brain regions. Significant associations of AD, RD, and FA were found for CGM measures of hyperglycemia and glucose variability but not for hypoglycemia. Finally, we observed a significant association between WM structure and cognitive ability in children with type 1 diabetes but not in control subjects.These results suggest vulnerability of the developing brain in young children to effects of type 1 diabetes associated with chronic hyperglycemia and glucose variability.

  View details for DOI 10.2337/dc13-1388

  View details for PubMedCentralID PMC3898758

• Real-time continuous glucose monitoring systems in the classroom/school environment. Diabetes technology & therapeutics Benassi, K., Drobny, J., Aye, T. 2013; 15 (5): 409-412

  Abstract

  Abstract Background: Children with type 1 diabetes (T1D) spend 4-7 h/day in school with very little supervision of their diabetes management. Therefore, families have become more dependent on technology, such as use of real-time continuous glucose monitoring (RT-CGM), to provide increased supervision of their diabetes management. We sought to assess the impact of RT-CGM use in the classroom/school environment. Subjects and Methods: Children with T1D using RT-CGM, their parents, and teachers completed a questionnaire about RT-CGM in the classroom/school environment. Results: The RT-CGM was tolerated well in the classroom/school environment. Seventy percent of parents, 75% of students, and 51% of teachers found RT-CGM useful in the classroom/school environment. The students found the device to be more disruptive than did their parents and teachers. However, all three groups agreed that RT-CGM increased their comfort with diabetes management at school. Conclusions: Our study suggests that RT-CGM is useful and not disruptive in the classroom/school environment. The development of education materials for teachers could further increase its acceptance in the classroom/school environment.

  View details for DOI 10.1089/dia.2012.0314

  View details for PubMedID 23530577

• White Matter Structural Differences in Young Children With Type 1 Diabetes: A Diffusion Tensor Imaging Study DIABETES CARE Aye, T., Barnea-Goraly, N., Ambler, C., Hoang, S., Schleifer, K., Park, Y., Drobny, J., Wilson, D. M., Reiss, A. L., Buckingham, B. A. 2012; 35 (11): 2167-2173

  Abstract

  To detect clinical correlates of cognitive abilities and white matter (WM) microstructural changes using diffusion tensor imaging (DTI) in young children with type 1 diabetes.Children, ages 3 to <10 years, with type 1 diabetes (n = 22) and age- and sex-matched healthy control subjects (n = 14) completed neurocognitive testing and DTI scans.Compared with healthy controls, children with type 1 diabetes had lower axial diffusivity (AD) values (P = 0.046) in the temporal and parietal lobe regions. There were no significant differences between groups in fractional anisotropy and radial diffusivity (RD). Within the diabetes group, there was a significant, positive correlation between time-weighted HbA(1c) and RD (P = 0.028). A higher, time-weighted HbA(1c) value was significantly correlated with lower overall intellectual functioning measured by the full-scale intelligence quotient (P = 0.03).Children with type 1 diabetes had significantly different WM structure (as measured by AD) when compared with controls. In addition, WM structural differences (as measured by RD) were significantly correlated with their HbA(1c) values. Additional studies are needed to determine if WM microstructural differences in young children with type 1 diabetes predict future neurocognitive outcome.

  View details for DOI 10.2337/dc12-0017

  View details for Web of Science ID 000311424100015

  View details for PubMedID 22966090

  View details for PubMedCentralID PMC3476914

• Analysis of the NovoTwist pen needle in comparison with conventional screw-thread needles. Journal of diabetes science and technology Aye, T. 2011; 5 (6): 1488-1489

  Abstract

  Administration of insulin via a pen device may be advantageous over a vial and syringe system. Hofman and colleagues introduce a new insulin pen needle, the NovoTwist, to simplify injections to a small group of children and adolescents. Their overall preferences and evaluation of the handling of the needle are reported in the study. This new needle has the potential to ease administration of insulin via a pen device that may increase both the use of a pen device and adherence to insulin therapy.

  View details for PubMedID 22226270

  View details for PubMedCentralID PMC3262719

• The Feasibility of Detecting Neuropsychologic and Neuroanatomic Effects of Type 1 Diabetes in Young Children DIABETES CARE Aye, T., Reiss, A. L., Kesler, S., Hoang, S., Drobny, J., Park, Y., Schleifer, K., Baumgartner, H., Wilson, D. M., Buckingham, B. A. 2011; 34 (7): 1458-1462

  Abstract

  To determine if frequent exposures to hypoglycemia and hyperglycemia during early childhood lead to neurocognitive deficits and changes in brain anatomy.In this feasibility, cross-sectional study, young children, aged 3 to 10 years, with type 1 diabetes and age- and sex-matched healthy control (HC) subjects completed neuropsychologic (NP) testing and magnetic resonance imaging (MRI) scans of the brain.NP testing and MRI scanning was successfully completed in 98% of the type 1 diabetic and 93% of the HC children. A significant negative relationship between HbA1c and Wechsler Intelligence Scale for Children (WISC) verbal comprehension was observed. WISC index scores were significantly reduced in type 1 diabetic subjects who had experienced seizures. White matter volume did not show the expected increase with age in children with type 1 diabetes compared with HC children (diagnosis by age interaction, P=0.005). A similar trend was detected for hippocampal volume. Children with type 1 diabetes who had experienced seizures showed significantly reduced gray matter and white matter volumes relative to children with type 1 diabetes who had not experienced seizures.It is feasible to perform MRI and NP testing in young children with type 1 diabetes. Further, early signs of neuroanatomic variation may be present in this population. Larger cross-sectional and longitudinal studies of neurocognitive function and neuroanatomy are needed to define the effect of type 1 diabetes on the developing brain.

  View details for DOI 10.2337/dc10-2164

  View details for Web of Science ID 000293261200003

  View details for PubMedID 21562318

  View details for PubMedCentralID PMC3120162

• Toward Closing the Loop: An Update on Insulin Pumps and Continuous Glucose Monitoring Systems ENDOCRINOLOGY AND METABOLISM CLINICS OF NORTH AMERICA Aye, T., Block, J., Buckingham, B. 2010; 39 (3): 609-?

  Abstract

  This article reviews current pump and continuous glucose monitoring therapy and what will be required to integrate these systems into closed-loop control. Issues with sensor accuracy, lag time, and calibration are discussed as well as issues with insulin pharmacodynamics, which result in a delayed onset of insulin action in a closed-loop system. A stepwise approach to closed-loop therapy is anticipated, where the first systems will suspend insulin delivery based on actual or predicted hypoglycemia. Subsequent systems may control to range, limiting the time spent in hyperglycemia by mitigating the effects of a missed food bolus or underestimate of consumed carbohydrates, while minimizing the risk of hypoglycemia.

  View details for DOI 10.1016/j.ecl.2010.05.005

  View details for Web of Science ID 000282146100011

  View details for PubMedID 20723823

  View details for PubMedCentralID PMC2938733

• Metformin Extended Release Treatment of Adolescent Obesity A 48-Week Randomized, Double-Blind, Placebo-Controlled Trial With 48-Week Follow-up ARCHIVES OF PEDIATRICS & ADOLESCENT MEDICINE Wilson, D. M., Abrams, S. H., Aye, T., Lee, P. D., Lenders, C., Lustig, R. H., Osganian, S. V., Feldman, H. A. 2010; 164 (2): 116-123

  Abstract

  Metformin has been proffered as a therapy for adolescent obesity, although long-term controlled studies have not been reported.To test the hypothesis that 48 weeks of daily metformin hydrochloride extended release (XR) therapy will reduce body mass index (BMI) in obese adolescents, as compared with placebo.Multicenter, randomized, double-blind, placebo-controlled clinical trial.The 6 centers of the Glaser Pediatric Research Network from October 2003 to August 2007.Obese (BMI > or = 95th percentile) adolescents (aged 13-18 years) were randomly assigned to the intervention (n = 39) or placebo groups. Intervention Following a 1-month run-in period, subjects following a lifestyle intervention program were randomized 1:1 to 48 weeks' treatment with metformin hydrochloride XR, 2000 mg once daily, or an identical placebo. Subjects were monitored for an additional 48 weeks. Main Outcome Measure Change in BMI, adjusted for site, sex, race, ethnicity, and age and metformin vs placebo.After 48 weeks, mean (SE) adjusted BMI increased 0.2 (0.5) in the placebo group and decreased 0.9 (0.5) in the metformin XR group (P = .03). This difference persisted for 12 to 24 weeks after cessation of treatment. No significant effects of metformin on body composition, abdominal fat, or insulin indices were observed.Metformin XR caused a small but statistically significant decrease in BMI when added to a lifestyle intervention program.clinicaltrials.gov Identifiers: NCT00209482 and NCT00120146.

  View details for Web of Science ID 000274139500001

  View details for PubMedID 20124139

  View details for PubMedCentralID PMC3499098