The relationship between BMI and insulin resistance and progression from single to multiple autoantibody positivity and type 1 diabetes among TrialNet Pathway to Prevention participants Journal Article

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Authors: Meah, F. A.; DiMeglio, L. A.; Greenbaum, C. J.; Blum, J. S.; Sosenko, J. M.; Pugliese, A.; Geyer, S.; Xu, P.; Evans-Molina, C.; Type 1 Diabetes TrialNet Study Group
Article Title: The relationship between BMI and insulin resistance and progression from single to multiple autoantibody positivity and type 1 diabetes among TrialNet Pathway to Prevention participants
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.
Journal Title: Diabetologia
Volume: 59
Issue: 6
ISSN: 1432-0428; 0012-186X
Publisher: Unknown  
Journal Place: Germany
Date Published: 2016
Start Page: 1186
End Page: 1195
Language: eng
DOI/URL:

10.1007/s00125-016-3924-5
Notes: LR: 20160909; GR: P30 DK097512/DK/NIDDK NIH HHS/United States; GR: R01 AI079065/AI/NIAID NIH HHS/United States; JID: 0006777; OTO: NOTNLM; 2015/10/21 [received]; 2016/02/24 [accepted]; 2016/03/19 [aheadofprint]; ppublish