TY - JOUR
T1 - 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
AU - Meah, Farah A.
AU - DiMeglio, Linda A.
AU - Greenbaum, Carla J.
AU - Blum, Janice S.
AU - Sosenko, Jay M.
AU - Pugliese, Alberto
AU - Geyer, Susan
AU - Xu, Ping
AU - Evans-Molina, Carmella
N1 - Funding Information:
The sponsor of the trial was the Type 1 Diabetes TrialNet Pathway to Prevention Study Group. Type 1 Diabetes TrialNet Pathway to Prevention Study Group is a clinical trials network funded by the National Institutes of Health (NIH) through the National Institute of Diabetes and Digestive and Kidney Diseases, the National Institute of Allergy and Infectious Diseases, and The Eunice Kennedy Shriver National Institute of Child Health and Human Development, through the cooperative agreements U01 DK061010, U01 DK061034, U01 DK061042, U01 DK061058, U01 DK085465, U01 DK085453, U01 DK085461, U01 DK085463, U01 DK085466, U01 DK085499, U01 DK085504, U01 DK085505, U01 DK085509, U01 DK103180, U01-DK103153, U01-DK085476, U01-DK103266 and the Juvenile Diabetes Research Foundation International (JDRF). This work was also partially supported by NIH grants R01 DK093954 and UC4 DK 104166 (to CEM), VA Merit Award I01BX001733 (to CEM) and JDRF grant SRA-2014-41 (to CEM, LAD and JSB). The contents of this article are solely the responsibility of the authors and do not necessarily represent the official views of the NIH, the US Department of Veterans Affairs or the United States Government, the JDRF or American Diabetes Association.
Publisher Copyright:
© 2016, Springer-Verlag Berlin Heidelberg.
PY - 2016/6/1
Y1 - 2016/6/1
N2 - 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.
AB - 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.
KW - Accelerator hypothesis
KW - BMI
KW - Diabetes in childhood
KW - HOMA1-IR
KW - Insulin sensitivity and resistance
KW - Pancreatic autoantibodies
KW - Pathway to Prevention
KW - Prediction and prevention of type 1 diabetes
KW - TrialNet
KW - Type 1 diabetes
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U2 - 10.1007/s00125-016-3924-5
DO - 10.1007/s00125-016-3924-5
M3 - Article
C2 - 26995649
AN - SCOPUS:84961223661
VL - 59
SP - 1186
EP - 1195
JO - Diabetologia
JF - Diabetologia
SN - 0012-186X
IS - 6
ER -