Farah A Meah1,2, Linda A DiMeglio3,4, Carla J Greenbaum5, Janice S Blum6, Jay M Sosenko7,8, Alberto Pugliese8,9, Susan Geyer10, Ping Xu10, Carmella Evans-Molina11,12. 1. Department of Medicine, Indiana University School of Medicine, 635 Barnhill Drive, MS 2031A, Indianapolis, IN, USA. 2. Department of Endocrinology, Edward Hines Junior VA Hospital, Hines, IL, USA. 3. Department of Pediatrics, Indiana University School of Medicine, Indianapolis, IN, USA. 4. Herman B Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, IN, USA. 5. Benaroya Research Institute, Diabetes Program, Seattle, WA, USA. 6. Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, IN, USA. 7. Diabetes Research Institute, Leonard Miller School of Medicine, University of Miami, Miami, FL, USA. 8. Department of Medicine, Division of Diabetes, Endocrinology & Metabolism, Leonard Miller School of Medicine, University of Miami, Miami, FL, USA. 9. Department of Microbiology and Immunology, Leonard Miller School of Medicine, University of Miami, Miami, FL, USA. 10. Health Informatics Institute, University of South Florida, Tampa, FL, USA. 11. Department of Medicine, Indiana University School of Medicine, 635 Barnhill Drive, MS 2031A, Indianapolis, IN, USA. cevansmo@iu.edu. 12. Herman B Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, IN, USA. cevansmo@iu.edu.
Abstract
AIMS/HYPOTHESIS: The incidence of type 1 diabetes is increasing at a rate of 3-5% per year. Genetics cannot fully account for this trend, suggesting an influence of environmental factors. The accelerator hypothesis proposes an effect of metabolic factors on type 1 diabetes risk. To test this in the TrialNet Pathway to Prevention (PTP) cohort, we analysed the influence of BMI, weight status and insulin resistance on progression from single to multiple islet autoantibodies (Aab) and progression from normoglycaemia to diabetes. METHODS: HOMA1-IR was used to estimate insulin resistance in Aab-positive PTP participants. Cox proportional hazards models were used to evaluate the effects of BMI, BMI percentile (BMI%), weight status and HOMA1-IR on the progression of autoimmunity or the development of diabetes. RESULTS: Data from 1,310 single and 1,897 multiple Aab-positive PTP participants were included. We found no significant relationships between BMI, BMI%, weight status or HOMA1-IR and the progression from one to multiple Aabs. Similarly, among all Aab-positive participants, no significant relationships were found between BMI, weight status or HOMA1-IR and progression to diabetes. Diabetes risk was modestly increased with increasing BMI% among the entire cohort, in obese participants 13-20 years of age and with increasing HOMA1-IR in adult Aab-positive participants. CONCLUSIONS/ INTERPRETATION: Analysis of the accelerator hypothesis in the TrialNet PTP cohort does not suggest a broad influence of metabolic variables on diabetes risk. Efforts to identify other potentially modifiable environmental factors should continue.
AIMS/HYPOTHESIS: The incidence of type 1 diabetes is increasing at a rate of 3-5% per year. Genetics cannot fully account for this trend, suggesting an influence of environmental factors. The accelerator hypothesis proposes an effect of metabolic factors on type 1 diabetes risk. To test this in the TrialNet Pathway to Prevention (PTP) cohort, we analysed the influence of BMI, weight status and insulin resistance on progression from single to multiple islet autoantibodies (Aab) and progression from normoglycaemia to diabetes. METHODS: HOMA1-IR was used to estimate insulin resistance in Aab-positive PTP participants. Cox proportional hazards models were used to evaluate the effects of BMI, BMI percentile (BMI%), weight status and HOMA1-IR on the progression of autoimmunity or the development of diabetes. RESULTS: Data from 1,310 single and 1,897 multiple Aab-positive PTP participants were included. We found no significant relationships between BMI, BMI%, weight status or HOMA1-IR and the progression from one to multiple Aabs. Similarly, among all Aab-positive participants, no significant relationships were found between BMI, weight status or HOMA1-IR and progression to diabetes. Diabetes risk was modestly increased with increasing BMI% among the entire cohort, in obeseparticipants 13-20 years of age and with increasing HOMA1-IR in adult Aab-positive participants. CONCLUSIONS/ INTERPRETATION: Analysis of the accelerator hypothesis in the TrialNet PTP cohort does not suggest a broad influence of metabolic variables on diabetes risk. Efforts to identify other potentially modifiable environmental factors should continue.
Entities:
Keywords:
Accelerator hypothesis; BMI; Diabetes in childhood; HOMA1-IR; Insulin sensitivity and resistance; Pancreatic autoantibodies; Pathway to Prevention; Prediction and prevention of type 1 diabetes; TrialNet; Type 1 diabetes
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