Browsing by Author "Shah, Viral N."
Now showing 1 - 10 of 11
Results Per Page
Sort Options
Item Changes in Basal and Bolus Insulin Requirements with Tirzepatide as an Adjunctive Therapy in Adults with Type 1 Diabetes Using Tandem Control-IQ(Springer, 2024) Karakus, Kagan E.; Klein, Matthew P.; Akturk, Halis K.; Shah, Viral N.; Medicine, School of MedicineIntroduction: This study was aimed at investigating changes in insulin requirements and glycemic outcomes in adults with type 1 diabetes (T1D) using Control IQ (Tandem Diabetes) automated insulin delivery system (AID) over 8 months of tirzepatide treatment. Methods: In this single-center, observational study, we collected demographic, A1c, weight, sensor glucose, and insulin dose data for adults with T1D who were using AID and initiated tirzepatide adjunct therapy for clinical indications (n = 11, median age 37, 64% female and mean body mass index of 39.6 kg/m2). Data were compared from baseline and over 8 months. Results: Within 2 months of tirzepatide treatment, there were significant reductions in total daily insulin [median (IQR) 73.9 (47.6-95.8) to 51.7 (46.7-66.8) units/day, p < 0.001], basal insulin [47 (28.2-51.8) to 32.4 (25.5-46.3) units/day, p < 0.001], and bolus insulin [31.4 (19.9-38.3) to 17.9 (14.9-22.2) units/day, p < 0.001] requirements. Insulin dose reduction from 2 to 8 months was modest. The frequency of user-initiated boluses did not differ throughout the study. Despite reductions in total insulin requirement, time in range (70-180 mg/dl) increased by 7%, A1c reduced by 0.5%, weight reduced by 9%, without increase in time below 70 mg/dl. Conclusions: This pilot study provides clinical guidance on insulin titration for adults with T1D who may initiate tirzepatide therapy. Based on the findings of this study, we recommend reducing 25% of total daily insulin dose at tirzepatide initiation in adults with T1D using AID with baseline A1c of less than 7.5%. Higher doses of tirzepatide were associated with greater weight loss, however, the reduction in insulin requirement was minimal.Item Consensus Report on Glucagon-Like Peptide-1 Receptor Agonists as Adjunctive Treatment for Individuals With Type 1 Diabetes Using an Automated Insulin Delivery System(Sage, 2024-11-08) Shah, Viral N.; Peters, Anne L.; Umpierrez, Guillermo E.; Sherr, Jennifer L.; Akturk, Halis Kaan; Aleppo, Grazia; Bally, Lia; Cengiz, Eda; Cinar, Ali; Dungan, Kathleen; Fabris, Chiara; Jacobs, Peter G.; Lal, Rayhan A.; Mader, Julia K.; Masharani, Umesh; Prahalad, Priya; Schmidt, Signe; Zijlstra, Eric; Ho, Cindy N.; Ayers, Alessandra T.; Tian, Tiffany; Aaron, Rachel E.; Klonoff, David C.; Medicine, School of MedicineWith increasing prevalence of obesity and cardiovascular diseases, there is a growing interest in the use of glucagon-like peptide-1 receptor agonists (GLP-1RAs) as an adjunct therapy in type 1 diabetes (T1D). The GLP-1RAs are currently not approved by the US Food and Drug Administration for the treatment of T1D in the absence of randomized controlled trials documenting efficacy and safety of these agents in this population. The Diabetes Technology Society convened a series of three consensus meetings of clinicians and researchers with expertise in diabetes technology, GLP-1RA therapy, and T1D management. The project was aimed at synthesizing current literature and providing conclusions on the use of GLP-1RA therapy as an adjunct to automated insulin delivery (AID) systems in adults with T1D. The expert panel members met virtually three times on January 17, 2024, and April 24, 2024, and August 14, 2024, to discuss topics ranging from physiology and outcomes of GLP-1RAs in T1D to limitations of current sensors, algorithms, and insulin for AID systems. The panelists also identified research gaps and future directions for research. The panelists voted to in favor of 31 recommendations. This report presents the consensus opinions of the participants that, in adults with T1D using AID systems, GLP-1RAs have the potential to (1) provide effective adjunct therapy and (2) improve glycemic and metabolic outcomes without increasing the risk of severe hypoglycemia or diabetic ketoacidosis.Item Determinants of Liraglutide Treatment Discontinuation in Type 1 Diabetes: A Post Hoc Analysis of ADJUNCT ONE and ADJUNCT TWO Randomized Placebo-Controlled Clinical Studies(Sage, 2024-12-24) Shah, Viral N.; Agesen, Rikke M.; Bardtrum, Lars; Christiansen, Erik; Snaith, Jennifer; Greenfield, Jerry R.; Medicine, School of MedicineIntroduction: Two phase 3 randomized controlled studies (ADJUNCT ONE (Clinicaltrials.gov: NCT01836523), ADJUNCT TWO (Clinicaltrials.gov: NCT02098395)) evaluated liraglutide (1.8, 1.2 or 0.6 mg) vs placebo in participants with type 1 diabetes (T1D) as an adjunct to insulin therapy. This paper aims to improve our understanding of the potential mechanisms leading to premature discontinuation of this treatment regimen. Methods: Post hoc comparisons were conducted on baseline characteristics and adverse event (AE) rates of participants completing and not completing the ADJUNCT studies due to AEs/lack of tolerance using summary tables and variance analysis. Results: Non-completers (liraglutide and placebo combined) had lower baseline body mass index (BMI) (ADJUNCT ONE: 27.8 kg/m2 vs 29.8 kg/m2, P < .0001; ADJUNCT TWO: 26.3 kg/m2 vs 29.2 kg/m2, P < .0001), longer duration of T1D (25.8 years vs 21.0 years, P < .0001; 24.1 years vs 21.0 years, P = .04), lower daily insulin doses by continuous infusion (46.4 U vs 57.3 U, P = .01; 40.9 U vs 57.4 U, P = .12) or multiple injections (58.4 U vs 68.5 U, P = .006; 56.0 U vs 65.8 U, P =.03) and a higher proportion of participants with undetectable C-peptide (91.5% vs 81.3%; 87.0% vs 84.9%) compared to completers. When analyzed by treatment group, only duration of T1D and C-peptide differed between completers and non-completers among liraglutide (and not placebo) participants. The AE rates were higher for non-completers. Conclusion: Individuals with longer-standing T1D and low levels of C-peptide at baseline were more likely to discontinue adjunctive liraglutide treatment due to AEs/lack of tolerance than individuals with residual insulin production. Lower BMI predicted a greater likelihood of non-completion for the included participants, regardless of treatment. These new findings may be relevant for clinical practice.Item Efficacy and Safety of Tirzepatide in Adults With Type 1 Diabetes: A Proof of Concept Observational Study(Sage, 2024-02-05) Akturk, Halis Kaan; Dong, Fran; Snell-Bergeon, Janet K.; Karakus, Kagan Ege; Shah, Viral N.; Medicine, School of MedicineBackground: Tirzepatide is approved by the United States Food and Drug Administration (FDA) for the management of type 2 diabetes. The efficacy and safety of this drug have not been studied in people with type 1 diabetes (T1D). Methods: In this single-center, retrospective, observational study, hemoglobin A1C (HbA1c), weight, body mass index (BMI), and continuous glucose monitoring (CGM) data were collected from electronic health records of adults with T1D at initiation of tirzepatide and at subsequent clinic visits over 8 months. Primary outcomes were reduction in HbA1c and percent change in body weight and secondary outcomes were change in CGM metrics and BMI over 8 months from baseline. Results: The mean (±SD) age of the 26 adults (54% female) with T1D was 42 ± 8 years with a mean BMI of 36.7 ± 5.3 kg/m2. There was significant reduction in HbA1c by 0.45% at 3 months and 0.59% at 8 months, and a significant reduction in body weight by 3.4%, 10.5%, and 10.1% at 3, 6, and 8 months after starting tirzepatide. Time in target range (TIR = 70-180 mg/dL) and time in tight target range (TITR = 70-140 mg/dL) increased (+12.6%, P = .002; +10.7%, P = .0016, respectively) and time above range (TAR >180 mg/dL) decreased (-12.6%, P = .002) at 3 months, and these changes were sustained over 8 months. The drug was relatively safe and well tolerated with only 2 patients discontinuing the medication. Conclusions: Tirzepatide significantly reduced HbA1c and body weight in adults with T1D. A randomized controlled trial is needed to establish efficacy and safety of this drug in T1D.Item Gender differences in diabetes self-care in adults with type 1 diabetes: Findings from the T1D Exchange clinic registry(Elsevier, 2018-10) Shah, Viral N.; Wu, Mengdi; Polsky, Sarit; Snell-Bergeon, Janet K.; Sherr, Jennifer L.; Cengiz, Eda; DiMeglio, Linda A.; Pop-Busui, Rodica; Mizokami-Stout, Kara; Foster, Nicole C.; Beck, Roy W.; Pediatrics, School of MedicineAims To evaluate gender differences in diabetes self-care components including glycemic, blood pressure and lipid control, utilization of diabetes technologies and acute diabetes complications in adults with type 1 diabetes. Methods A total of 9,481 participants >18 years were included in the analysis, 53% were female. Variables of interest included glycemic control measured by HbA1c, systolic/diastolic blood pressures, presence of dyslipidemia, insulin delivery modality, and rates of acute complications. Results Glycemic control was similar in women and men (mean HbA1c in both groups: 8.1% ± 1.6% (64 ± 16 mmol/mol), (p = 0.54). More women used insulin pump therapy (66% vs. 59%, p < 0.001) but use of sensor technology was similar (p < = 0.42). Women had higher rates of diabetic ketoacidosis (DKA) (5% vs. 3%, p < 0.001) and eating disorders (1.7% vs. 0.1%, p < 0.001). Severe hypoglycemia rates were not different between men and women (p = 0.42). Smoking (6% vs 4%, p < 0.001), systolic (125 ± 14.2 vs. 121 ± 14.4, p < 0.001) and diastolic blood pressure (73.3 ± 9.5 vs. 72.2 ± 9.3, p < 0.001) and rate of dyslipidemia (28% vs. 23%, p < 0.001) were higher in men. Conclusion While glycemic control in type 1 diabetes was similar regardless of gender, rates of DKA and eating disorders were higher in women while rates of smoking, hypertension and dyslipidemia were higher in men.Item Health-related quality of life in parents and partners of people with type 1 diabetes: Development and validation of type 1 diabetes and life (T1DAL) measures(American Psychological Association, 2021) Hilliard, Marisa E.; Minard, Charles G.; Marrero, David G.; de Wit, Maartje; DuBose, Stephanie N.; Verdejo, Alandra; Jaser, Sarah S.; Kruger, Davida; Monzavi, Roshanak; Shah, Viral N.; Wadwa, R. Paul; Weinstock, Ruth S.; Thompson, Debbe; Cao, Viena T.; Anderson, Barbara J.; Medicine, School of MedicineIntroduction: Despite the significant impact of type 1 diabetes (T1D) on family, few instruments are available to assess health-related quality of life (HRQOL) among family members of people with T1D. This study aimed to develop and evaluate the psychometric properties of new measures of diabetes-specific HRQOL for parents and partners of people with T1D. We report on the multistep development and validation process for the self-report Type 1 Diabetes and Life (T1DAL) measures, with versions for parents of youth age <8, 8-11, 12-17, and 18-25 years, and for partners of people age ≥18 years with T1D. Method: First, we conducted qualitative interviews (total parents/partners n = 38) to develop draft measures and piloted them (total n = 20). Next, we tested the measures' psychometric properties. Participants (total across versions n = 813) at six T1D Exchange Clinic Network sites completed the appropriate T1DAL measure and validated measures of related constructs. We then reduced each T1DAL measure to 20-30 items in length based on psychometric data and participant feedback. Eleven participants reviewed the final measures via cognitive debriefing. Results: The T1DAL measures for parents and partners demonstrated good internal consistency (α = .80-.88) and test-retest reliability (r = .73-.86). Correlations with measures of general quality of life, generic and diabetes-specific HRQOL, and diabetes burden demonstrated construct validity. Factor analyses identified 3-4 subscales/measure. Participants reported being satisfied with the shortened measures, which took 5-10 minutes to complete. Discussion: The new T1DAL measures for parents and partners of people with T1D are reliable, valid, and ready for use in research and clinical settings.Item High residual C-peptide likely contributes to glycemic control in type 1 diabetes(American Society for Clinical Investigation, 2020-01-02) Rickels, Michael R.; Evans-Molina, Carmella; Bahnson, Henry T.; Ylescupidez, Alyssa; Nadeau, Kristen J.; Hao, Wei; Clements, Mark A.; Sherr, Jennifer L.; Pratley, Richard E.; Hannon, Tamara S.; Shah, Viral N.; Miller, Kellee M.; Greenbaum, Carla J.; Medicine, School of MedicineBACKGROUND Residual C-peptide is detected in many people for years following the diagnosis of type 1 diabetes; however, the physiologic significance of low levels of detectable C-peptide is not known. METHODS We studied 63 adults with type 1 diabetes classified by peak mixed-meal tolerance test (MMTT) C-peptide as negative (<0.007 pmol/mL; n = 15), low (0.017–0.200; n = 16), intermediate (>0.200–0.400; n = 15), or high (>0.400; n = 17). We compared the groups’ glycemia from continuous glucose monitoring (CGM), β cell secretory responses from a glucose-potentiated arginine (GPA) test, insulin sensitivity from a hyperinsulinemic-euglycemic (EU) clamp, and glucose counterregulatory responses from a subsequent hypoglycemic (HYPO) clamp. RESULTS Low and intermediate MMTT C-peptide groups did not exhibit β cell secretory responses to hyperglycemia, whereas the high C-peptide group showed increases in both C-peptide and proinsulin (P ≤ 0.01). All groups with detectable MMTT C-peptide demonstrated acute C-peptide and proinsulin responses to arginine that were positively correlated with peak MMTT C-peptide (P < 0.0001 for both analytes). During the EU-HYPO clamp, C-peptide levels were proportionately suppressed in the low, intermediate, and high C-peptide compared with the negative group (P ≤ 0.0001), whereas glucagon increased from EU to HYPO only in the high C-peptide group compared with negative (P = 0.01). CGM demonstrated lower mean glucose and more time in range for the high C-peptide group. CONCLUSION These results indicate that in adults with type 1 diabetes, β cell responsiveness to hyperglycemia and α cell responsiveness to hypoglycemia are observed only at high levels of residual C-peptide that likely contribute to glycemic control. FUNDING Funding for this work was provided by the Leona M. and Harry B. Helmsley Charitable Trust, the National Center for Advancing Translational Sciences, and the National Institute of Diabetes and Digestive and Kidney Diseases.Item Prediction of Incident Diabetic Retinopathy in Adults With Type 1 Diabetes Using Machine Learning Approach: An Exploratory Study(Sage, 2024-10-28) Montaser, Eslam; Shah, Viral N.; Medicine, School of MedicineBackground: Early detection and intervention are crucial for preventing vision-threatening diabetic retinopathy (DR) in adults with type 1 diabetes (T1D). This exploratory study uses machine learning on continuous glucose monitoring (CGM) data to identify factors influencing DR and predict high-risk individuals for timely intervention. Methods: Between June 2018 and March 2022, adults with T1D with incident DR or no retinopathy (control) were identified. The CGM data were collected retrospectively for up to seven years before the date of defining incident DR or no retinopathy. A mixture of three machine learning algorithms was trained and evaluated in two different scenarios, using different glycemic features extracted from CGM traces (scenario 1), and the two principal components (two PCs; exposure to hyperglycemia and hypoglycemia risk) of those features (scenario 2). Classifiers were evaluated through 10-fold cross-validation using the receiver operating characteristic area under the curve (AUC-ROC) to select the best classification model. Results: The CGM data of 30 adults with incident DR (mean±SD age of 21.2±9.4 years, glycated hemoglobin [HbA1c] of 8.6%±1.0%, and body mass index [BMI] of 24.5±4.8 kg/m2) and 30 adults without DR (age of 41.8±14.7 years, HbA1c of 7.0%±0.9%, and BMI of 26.2±3.6 kg/m2) were included in this analysis. In scenario 2, classifiers outperformed scenario 1, resulting in an average AUC-ROC increase to 0.92 for two of three models, indicating that the two PCs captured vital classification data, representing the most discriminative aspects and enhancing model performance. Conclusion: Machine learning approaches using CGM data may have potential to aid in identifying adults with T1D at risk of DR.Item Reduced Efficacy of Glucagon-Like Peptide-1 Receptor Agonists Therapy in People With Type 1 Diabetes and Genetic Forms of Obesity(Sage, 2024-04-17) Klein, Matthew P.; Akturk, Halis Kaan; Snell-Bergeon, Janet K.; Shah, Viral N.; Medicine, School of MedicineBackground: Once weekly Glucagon-Like Peptide-1 Receptor Agonists (GLP-1 RA) have been shown to improve glycemic outcomes and cause significant weight loss. However, 9% to 27% of individuals have little or no response to these drugs. In this article, we investigated the efficacy of GLP-1 RA therapy among adults with type 1 diabetes and obesity likely related to genetic mutations compared with obesity likely unrelated to genetic mutations. Methods: In this retrospective study, we compared body weight and glycated hemoglobin (HbA1c) change with the use of GLP-1 RA therapy (including a dual agonist, Tirzepatide) over six months among adults with type 1 diabetes and obesity likely (n = 11, median age 39.5 years with a median BMI of 43.0 kg/m2) versus unlikely related to genetic mutation(s) (n = 15, median age 45.8 years with a median BMI of 38.7 kg/m2). Results: Six months of GLP-1 RA treatment resulted in a numerically lower reduction of weight (-5.75 ± 9.46 kg vs -8.65 ± 9.36 kg, P = .44) and HbA1c (-0.28 ± 0.96% vs -0.43 ± 0.57%, P = .64) among individuals with obesity likely versus unlikely related to a genetic mutation(s), respectively. Fewer individuals with genetic obesity met goal weight loss ≥5% or HbA1c decrease ≥0.4% than did individuals with obesity unlikely related to a genetic cause (36.4% vs 80.0%, P = .04). Conclusions: The weight loss and glycemic lowering effects of GLP-1 RA therapy may be decreased in people with type 1 diabetes and obesity likely related to genetic causes. Further research is needed to understand GLP-1 RA mechanisms via energy regulating genes.Item Safety and Efficacy of Switching SAR341402 Insulin Aspart and Originator Insulin Aspart vs Continuous Use of Originator Insulin Aspart in Adults With Type 1 Diabetes: The GEMELLI X Trial(Sage, 2024-02-29) Shah, Viral N.; Al-Karadsheh, Amer; Barnes, Cathy; Mandry, Jose; Nakhle, Samer; Wernicke-Panten, Karin; Kramer, Daniel; Schmider, Wolfgang; Pierre, Suzanne; Teichert, Lenore; Rotthaeuser, Baerbel; Mukherjee, Bhaswati; Bailey, Timothy S.; Medicine, School of MedicineBackground: SAR341402 insulin aspart (SAR-Asp) is a rapid-acting insulin analog developed as an interchangeable biosimilar to the marketed insulin aspart reference product (NovoLog; NN-Asp). GEMELLI X was a randomized controlled trial to assess outcomes with a biosimilar in line with the US Food and Drug Administration requirements for designation as an interchangeable biosimilar. This report assessed whether multiple switches between SAR-Asp and NN-Asp lead to equivalent safety and efficacy compared with continuous use of NN-Asp in adults with type 1 diabetes (T1D) treated with multiple daily injections, using once-daily insulin glargine U100 (Lantus) as the basal insulin. Methods: This open-label randomized (1:1), parallel-group, phase 3 trial compared four × four weeks of alternating use of individually titrated SAR-Asp and NN-Asp (NN-Asp for first four weeks, SAR-Asp in last four weeks; switching group) vs 16 weeks of continuous use of NN-Asp (nonswitching group). End points included pharmacokinetics, immunogenicity, adverse events, hypoglycemia, insulin dose, and change in efficacy parameters. Results: Of the 210 patients randomized, 200 (95.5%) completed the trial. Patients assigned to switching group (n = 104) and nonswitching group (n = 106) showed similar safety and tolerability, including anti-insulin aspart antibody responses, adverse events, and hypoglycemia. At week 16, there was no relevant difference between switching vs nonswitching groups in the change from baseline in glycated hemoglobin (least square [LS] mean difference = 0.05% [95% confidence interval [CI] = -0.13, 0.22]; 0.50 mmol/mol [-1.40, 2.39]), fasting plasma glucose (LS mean difference = 0.23 mmol/L [95% CI = -1.08, 1.53]; 4.12 mg/dL [-19.38, 27.62]), and changes in insulin dosages. Conclusions: Alternating doses of SAR-Asp and NN-Asp compared with continuous use of NN-Asp showed similar safety, immunogenicity, and clinical efficacy in adults with T1D. This study supports interchangeability between SAR-Asp and NN-Asp in T1D management.