The Role of Age and Excess Body Mass Index in Progression to Type 1 Diabetes in At-Risk Adults

the Type 1 Diabetes TrialNet Study Group

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17 Scopus citations


Background: Given the global rise in both type 1 diabetes incidence and obesity, the role of body mass index (BMI) on type 1 diabetes pathophysiology has gained great interest. Sustained excess BMI in pediatric participants of the TrialNet Pathway to Prevention (PTP) cohort increased risk for progression to type 1 diabetes, but the effects of age and obesity in adults remain largely unknown. Objective: To determine the effect of age and sustained obesity on the risk for type 1 diabetes in adult participants in the TrialNet PTP cohort (i.e., nondiabetic autoantibody-positive relatives of patients with type 1 diabetes). Research Design and Methods: Longitudinally accumulated BMI .25 kg/m2 was calculated to generate a cumulative excess BMI (ceBMI) for each participant, with ceBMI values $0 kg/m2 and $5 kg/m2 representing sustained overweight or obese status, respectively. Recursive partitioning analysis yielded sex- and age-specific thresholds for ceBMI that confer the greatest risk for type 1 diabetes progression. Results: In this cohort of 665 adults (age 20 to 50 years; median follow-up, 3.9 years), 49 participants developed type 1 diabetes. Age was an independent protective factor for type 1 diabetes progression (hazard ratio, 0.95; P = 0.008), with a threshold of .35 years that reduced risk for type 1 diabetes. In men age .35 years and women age,35 years, sustained obesity (ceBMI $5 kg/m2) increased the risk for type 1 diabetes. Conclusions: Age is an important factor for type 1 diabetes progression in adults and influences the impact of elevated BMI, indicating an interplay of excess weight, age, and sex in adult type 1 diabetes pathophysiology.

Original languageEnglish (US)
Pages (from-to)4596-4603
Number of pages8
JournalJournal of Clinical Endocrinology and Metabolism
Issue number12
StatePublished - Dec 1 2017

Bibliographical note

Funding Information:
Financial Support: The sponsor of the trial was the Type 1 Diabetes TrialNet PTP Study Group. The Type 1 Diabetes TrialNet PTP 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, and U01-DK103266) and the Juvenile Diabetes Research Foundation International (JDRF). This work was also partially supported by the NIH grant K12-DK-094726 (C.T.F.) and U01-DK-103180-01 (M.J.R.) and a JDRF Strategic Research Agreement (C.E.-M.). The contents of this article are solely the responsibility of the authors and do not necessarily represent the official views of the NIH or the JDRF.

Publisher Copyright:
Copyright © 2017 Endocrine Society.


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