Rayhan Lal

All Publications

• An Intolerable Burden: Suicide, Intended Self-Injury and Diabetes. Canadian journal of diabetes Barnard-Kelly, K. D., Naranjo, D., Majidi, S., Akturk, H. K., Breton, M., Courtet, P., Olie, E., Lal, R. A., Johnson, N., Atkinson, M., Renard, E. 2020

  View details for DOI 10.1016/j.jcjd.2020.01.008

  View details for PubMedID 32305294

• Insulin Pumps. Diabetes technology & therapeutics Lal, R., Leelarathna, L. 2020; 22 (S1): S17?S31

  View details for DOI 10.1089/dia.2020.2502

  View details for PubMedID 32069156

• 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

• Fast-Acting Insulin Aspart Use with the MiniMed? 670G System. Diabetes technology & therapeutics Hsu, L. J., Buckingham, B. A., Basina, M., Ekhlaspour, L., von Eyben, R., Wang, J., Lal, R. A. 2020

  Abstract

  BACKGROUND This study assessed the efficacy and safety of ultra-rapid insulin Fiasp® in the hybrid closed-loop MiniMed? 670G system. METHODS This was a pilot randomized, double-blinded, cross-over study among established MiniMed? 670G users comparing percent time in range (TIR) and hypoglycemia for Novolog® and Fiasp®. Following two weeks optimization with their home insulin, participants were randomized to receive Novolog® or Fiasp® for two weeks, followed by the other insulin for the next two weeks. Data from the second week of blinded insulin use was analyzed to allow one week for 670G adaptation. During the second week, individuals were asked to eat the same breakfast for three days to assess differences in meal pharmacodynamics. RESULTS Nineteen adults were recruited with mean age of 40±18 years, diabetes duration of 27±12 years and median HbA1c of 7.1 (6.9,7.5)%, using 0.72 (0.4,1.2) units/kg/day. For Novolog® and Fiasp® respectively the %TIR (70-180mg/dL) was 75.3±9.5 and 78.4 ±9.3; %time <70mg/dL was 3.1±2.1 and 2.3±2.0; %time >180mg/dL was 21.6±9.0 and 19.3±8.9; mean glucose was 147±12 and 146±12mg/dL; coefficient of variation was 28.6±4.5% and 26.8±4.4%; %time in Auto Mode 86.4±9.2 and 84.4±9.2. All comparisons were non-significant for insulin type. Total daily dose (Novolog® 48.8±28.4 vs. Fiasp® 52.4±31.7 units; p=0.01) and daily basal (Novolog® 17.6 (15.5,33.8) vs. Fiasp® 19.1 (15.3,38.5) units; p=0.07) correlated with TIR and %time >180mg/dL. For insulin delivery in Auto Mode there was no statistical difference in total daily dose or daily basal between arms. Paired analysis for matched breakfast meals revealed no significant differences in time to maximum glucose, peak glucose or glucose excursion. CONCLUSIONS In this pilot study the use of either Novolog® or Fiasp® in a commercially available MiniMed? 670G system operating in Auto Mode resulted in clinically similar glycemic outcomes, with a slight increase in daily insulin requirements using Fiasp®.

  View details for DOI 10.1089/dia.2020.0083

  View details for PubMedID 32520594

• 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

• Suicide and Self-inflicted Injury in Diabetes: A Balancing Act. Journal of diabetes science and technology Barnard-Kelly, K. D., Naranjo, D., Majidi, S., Akturk, H. K., Breton, M., Courtet, P., Olie, E., Lal, R. A., Johnson, N., Renard, E. 2019: 1932296819891136

  Abstract

  Glycemic control in type 1 diabetes mellitus (T1DM) remains a challenge for many, despite the availability of modern diabetes technology. While technologies have proven glycemic benefits and may reduce excess mortality in some populations, both mortality and complication rates remain significantly higher in T1DM than the general population. Diabetes technology can reduce some burdens of diabetes self-management, however, it may also increase anxiety, stress, and diabetes-related distress. Additional workload associated with diabetes technologies and the dominant focus on metabolic control may be at the expense of quality-of-life. Diabetes is associated with significantly increased risk of suicidal ideation, self-harm, and suicide. The risk increases for those with diabetes and comorbid mood disorder. For example, the prevalence of depression is significantly higher in people with diabetes than the general population, and thus, people with diabetes are at even higher risk of suicide. The Center for Disease Control and Prevention reported a 24% rise in US national suicide rates between 1999 and 2014, the highest in 30 years. In the United Kingdom, 6000 suicides occur annually. Rates of preventable self-injury mortality stand at 29.1 per 100 000 population. Individuals with diabetes have an increased risk of suicide, being three to four times more likely to attempt suicide than the general population. Furthermore, adolescents aged 15 to 19 are most likely to present at emergency departments for self-inflicted injuries (9.6 per 1000 visits), with accidents, alcohol-related injuries, and self-harm being the strongest risk factors for suicide, the second leading cause of death among 10 to 24 year olds. While we have developed tools to improve glycemic control, we must be cognizant that the psychological burden of chronic disease is a significant problem for this vulnerable population. It is crucial to determine the psychosocial and behavioral predictors to uptake and continued use of technology in order to aid the identification of those individuals most likely to realize benefits of any intervention as well as those individuals who may require more support to succeed with technology.

  View details for DOI 10.1177/1932296819891136

  View details for PubMedID 31801353

• Perspectives on long-acting growth hormone therapy in children and adults. Archives of endocrinology and metabolism Lal, R. A., Hoffman, A. R. 2019; 63 (6): 601?7

  Abstract

  Growth hormone therapy with daily injections of recombinant human growth hormone has been available since 1985, and is shown to be safe and effective treatment for short stature in children and for adult growth hormone deficiency. In an effort to produce a product that would improve patient adherence, there has been a strong effort from industry to create a long acting form of growth hormone to ease the burden of use. Technologies used to increase half-life include depot formulations, PEGylated formulations, pro-drug formulations, non-covalent albumin binding growth hormone and growth hormone fusion proteins. At present, two long acting formulations are on the market in China and South Korea, and several more promising agents are under clinical investigation at various stages of development throughout the world. Arch Endocrinol Metab. 2019;63(6):601-7.

  View details for DOI 10.20945/2359-3997000000190

  View details for PubMedID 31939485

• 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

• Realizing a Closed-Loop (Artificial Pancreas) System for the Treatment of Type 1 Diabetes. Endocrine reviews Lal, R. A., Ekhlaspour, L., Hood, K., Buckingham, B. 2019

  Abstract

  Recent, rapid changes in the treatment of type 1 diabetes have allowed for commercialization of an "artificial pancreas" which is better described as a closed-loop controller of insulin delivery. This review presents the current state of closed-loop control systems and expected future developments with a discussion of the human factor issues in allowing automation of glucose control. The goal of these systems is to minimize or prevent both short and long-term complications from diabetes and to decrease the daily burden of managing diabetes. The closed-loop systems are generally very effective and safe at night, have allowed for improved sleep and have decreased the burden of diabetes management overnight. However, there are still significant barriers to achieving excellent daytime glucose control while simultaneously decreasing the burden of daytime diabetes management. These systems utilize a subcutaneous continuous glucose sensor, an algorithm that accounts for the current glucose and rate of change of the glucose, and the amount of insulin which has already been delivered in order to safely deliver insulin to control hyperglycemia, while minimizing the risk of hypoglycemia. The future challenge will be to allow for full closed-loop control with minimal burden on the patient during the day alleviating meal announcements, carbohydrate counting, alerts and maintenance. The human factors involved with interfacing with a closed-loop system and allowing the system to take control of diabetes management are significant. It is important to find a balance between enthusiasm and realistic expectations and experiences with closed loop.

  View details for DOI 10.1210/er.2018-00174

  View details for PubMedID 31276160

• 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

• 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

• 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

• Fluoroscopic-assisted laparoscopic retrieval of retained glucose sensor wire from the omentum. Clinical case reports Sang, A. X., Lal, R., August, A., Danzer, E., Buckingham, B., Mueller, C. M. 2019; 7 (9): 1717?20

  Abstract

  We describe a case in which retained wires from a continuous glucose monitor were removed from the abdominal wall and peritoneum of a 6-year-old boy. We highlight a concern for continuous glucose monitor use in children and discuss surgical techniques used to retrieve tiny, mobile objects from complex body cavities.

  View details for DOI 10.1002/ccr3.2348

  View details for PubMedID 31534734

  View details for PubMedCentralID PMC6745354

• 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

• Long-Acting Growth Hormone Preparations in the Treatment of Children. Pediatric endocrinology reviews : PER Lal, R. A., Hoffman, A. R. 2018; 16 (Suppl 1): 162?67

  Abstract

  Human growth hormone (hGH), which had been in use since 1958, was supplanted by recombinant human growth hormone (rhGH) in 1985 for those with growth hormone deficiency (GHD). Adherence to daily subcutaneous growth hormone is challenging for patients. Thus, several companies have pursued the creation of long acting rhGH. These agents can be divided broadly into depot formulations, PEGylated formulations, pro-drug formulations, non-covalent albumin binding GH and GH fusion proteins. Nutropin Depot is the only long acting rhGH ever approved by the U.S. Food and Drug Administration, and it was removed from the market in 2004. Of the approximately seventeen candidate drugs, only a handful remain under active clinical investigation or are commercially available.

  View details for PubMedID 30378794

• 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

• Advances in Care for Insulin-Requiring Patients Without Closed Loop DIABETES TECHNOLOGY & THERAPEUTICS Lal, R. A., Buckingham, B., Maahs, D. M. 2018; 20: 85?91

  View details for DOI 10.1089/dia.2018.0084

  View details for Web of Science ID 000435570300012

• Postmenopausal Hyperandrogenism. Journal of women's health care Lal, R. A., Basina, M. 2018; 7 (1)

  View details for DOI 10.4172/2167-0420.1000e132

  View details for PubMedID 32284912

• A Case Report of Hypoglycemia and Hypogammaglobulinemia: DAVID syndrome in a patient with a novel NFKB2 mutation. journal of clinical endocrinology and metabolism Lal, R. A., Bachrach, L. K., Hoffman, A. R., Inlora, J., Rego, S., Snyder, M. P., Lewis, D. B. 2017

  Abstract

  DAVID syndrome (Deficient Anterior pituitary with Variable Immune Deficiency) is a rare disorder in which children present with symptomatic ACTH deficiency preceded by hypogammaglobulinemia from B-cell dysfunction with recurrent infections, termed common variable immunodeficiency (CVID). Subsequent whole exome sequencing studies have revealed germline heterozygous C-terminal mutations of NFKB2 as either a cause of DAVID syndrome or of CVID without clinical hypopituitarism. However, to the best of our knowledge there have been no cases in which the endocrinopathy has presented in the absence of a prior clinical history of CVID.A previously healthy 7 year-old boy with no history of clinical immunodeficiency, presented with profound hypoglycemia and seizures. He was found to have secondary adrenal insufficiency and was started on glucocorticoid replacement. An evaluation for autoimmune disease, including for anti-pituitary antibodies, was negative. Evaluation unexpectedly revealed hypogammaglobulinemia (decreased IgG, IgM, and IgA). He had moderately reduced serotype-specific IgG responses following pneumococcal polysaccharide vaccine. Subsequently, he was found to have growth hormone (GH) deficiency. Six years after initial presentation, whole exome sequencing revealed a novel de novo heterozygous NFKB2 missense mutation c.2596A>C (p.Ser866Arg) in the C-terminal region predicted to abrogate the processing of the p100 NFKB2 protein to its active p52 form.Isolated early-onset ACTH deficiency is rare and C-terminal region NFKB2 mutations should be considered as an etiology even in the absence of a clinical history of CVID. Early immunologic evaluation is indicated in the diagnosis and management of isolated ACTH deficiency.

  View details for DOI 10.1210/jc.2017-00341

  View details for PubMedID 28472507

• 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

• An unusual cause of hyperglycemia JOURNAL OF POSTGRADUATE MEDICINE Lal, R., Loomba-Albrecht, L. A., Bremer, A. A. 2011; 57 (4): 343?46

  View details for DOI 10.4103/0022-3859.90092

  View details for Web of Science ID 000298626200018

  View details for PubMedID 22120869

• Amyloid-beta and Glucose Metabolism in Alzheimer's Disease JOURNAL OF ALZHEIMERS DISEASE Furst, A. J., Lal, R. A. 2011; 26: 105-116

  Abstract

  This study used PET with the amyloid-? (A?) imaging agent 11 C Pittsburgh Compound-B (PIB) and the glucose metabolic tracer 18F-fluorodeoxyglucose (FDG) to map the relationship of A? deposition to regional glucose metabolism in Alzheimer's disease (AD). Comparison of 13 AD patients' FDG scans with 11 healthy controls confirmed a typical temporo-parietal hypometabolic pattern in AD. In contrast, PIB distribution-volume-ratios showed a distinct pattern of specific tracer retention in fronto-temporo-parietal regions and striatum in AD with peaks in left frontal cortex, precuneus, temporal cortex, striatum and right posterior cingulate. There were no region-to-region or within region correlations between FDG and PIB uptake in PIB positive AD patients but when the impact of A? load on glucose metabolism was assessed via probabilistic maps, increased amyloid burden was coupled with decreased metabolism in temporo-parietal regions and the posterior cingulate. However, importantly, severe A? burden was not associated with comparable metabolic decreases in large parts of the frontal lobes, the striatum and the thalamus.

  View details for DOI 10.3233/JAD-2011-0066

  View details for Web of Science ID 000297842800008

  View details for PubMedID 21971455

• Amyloid-beta and Glucose Metabolism in Alzheimer's Disease HANDBOOK OF IMAGING THE ALZHEIMER BRAIN Furst, A. J., Lal, R. A., Ashford, J. W., Rosen, A., Adamson, M., Bayley, P., Sabri, O., Furst, A., Black, S. E., Weiner, M. 2011; 2: 235?46

  View details for DOI 10.3233/978-1-60750-793-2-235

  View details for Web of Science ID 000351445400023

• Striatal Dopamine and Working Memory CEREBRAL CORTEX Landau, S. M., Lal, R., O'Neil, J. P., Baker, S., Jagust, W. J. 2009; 19 (2): 445-454

  Abstract

  Recent studies have emphasized the importance of dopamine projections to the prefrontal cortex (PFC) for working memory (WM) function, although this system has rarely been studied in humans in vivo. However, dopamine and PFC activity can be directly measured with positron emission tomography (PET) and functional magnetic resonance imaging (fMRI), respectively. In this study, we examined WM capacity, dopamine, and PFC function in healthy older participants in order to test the hypothesis that there is a relationship between these 3 factors. We used the PET tracer 6-[18F]fluoro-L-m-tyrosine to measure dopamine synthesis capacity in the striatum (caudate, putamen), and event-related fMRI to measure brain activation during different epochs (cue, delay, probe) of a WM task. Caudate (but not putamen) dopamine correlated positively with WM capacity, whereas putamen (but not caudate) dopamine correlated positively with motor speed. In addition, delay-related fMRI activation in a left inferior prefrontal region was related to both caudate dopamine and task accuracy, suggesting that this may be a critical site for the integration of WM maintenance processes. These results provide new evidence that striatal dopaminergic function is related to PFC-dependent functions, particularly brain activation and behavioral performance during WM tasks.

  View details for DOI 10.1093/cercor/bhn095

  View details for Web of Science ID 000262518800019

  View details for PubMedID 18550595

  View details for PubMedCentralID PMC2733326

• A beta Amyloid and Glucose Metabolism in Three Variants of Primary Progressive Aphasia ANNALS OF NEUROLOGY Rabinovici, G. D., Jagust, W. J., Furst, A. J., Ogar, J. M., Racine, C. A., Mormino, E. C., O'Neil, J. P., Lal, R. A., Dronkers, N. F., Miller, B. L., Gorno-Tempini, M. L. 2008; 64 (4): 388-401

  Abstract

  Alzheimer's disease (AD) is found at autopsy in up to one third of patients with primary progressive aphasia (PPA), but clinical features that predict AD pathology in PPA are not well defined. We studied the relationships between language presentation, Abeta amyloidosis, and glucose metabolism in three PPA variants using [11C]-Pittsburgh compound B ([11C]PIB) and [18F]-labeled fluorodeoxyglucose positron emission tomography ([18F]FDG-PET).Patients meeting PPA criteria (N = 15) were classified as logopenic aphasia (LPA), progressive nonfluent aphasia (PNFA), or semantic dementia (SD) based on language testing. [11C]PIB distribution volume ratios were calculated using Logan graphical analysis (cerebellar reference). [18F]FDG images were normalized to pons. Partial volume correction was applied.Elevated cortical PIB (by visual inspection) was more common in LPA (4/4 patients) than in PNFA (1/6) and SD (1/5) (p < 0.02). In PIB-positive PPA, PIB uptake was diffuse and indistinguishable from the pattern in matched AD patients (n = 10). FDG patterns were focal and varied by PPA subtype, with left temporoparietal hypometabolism in LPA, left frontal hypometabolism in PNFA, and left anterior temporal hypometabolism in SD. FDG uptake was significant asymmetric (favoring left hypometabolism) in PPA (p < 0.005) but not in AD.LPA is associated with Abeta amyloidosis, suggesting that subclassification of PPA based on language features can help predict the likelihood of AD pathology. Language phenotype in PPA is closely related to metabolic changes that are focal and anatomically distinct between subtypes, but not to amyloid deposition patterns that are diffuse and similar to AD.

  View details for DOI 10.1002/ana.21451

  View details for Web of Science ID 000260845000007

  View details for PubMedID 18991338

  View details for PubMedCentralID PMC2648510