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

J Clin Endocrinol Metab. 2017 Dec 1;102(12):4596-4603. doi: 10.1210/jc.2017-01490.


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.

Trial registration: NCT00097292.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aging / pathology*
  • Algorithms
  • Autoantibodies
  • Body Mass Index
  • Cohort Studies
  • Diabetes Mellitus, Type 1 / pathology*
  • Disease Progression
  • Female
  • Humans
  • Insulin Antibodies / analysis
  • Longitudinal Studies
  • Male
  • Middle Aged
  • Obesity / pathology*
  • Overweight / pathology
  • Risk Factors
  • Sex Characteristics
  • Socioeconomic Factors
  • Young Adult


  • Autoantibodies
  • Insulin Antibodies

Associated data