Diabetes autoantibodies do not predict progression to diabetes in adults: the Diabetes Prevention Program

Diabet Med. 2014 Sep;31(9):1064-8. doi: 10.1111/dme.12437. Epub 2014 Apr 9.


Aims: To determine if the presence of diabetes autoantibodies predicts the development of diabetes among participants in the Diabetes Prevention Program.

Methods: A total of 3050 participants were randomized into three treatment groups: intensive lifestyle intervention, metformin and placebo. Glutamic acid decarboxylase (GAD) 65 autoantibodies and insulinoma-associated-2 autoantibodies were measured at baseline and participants were followed for 3.2 years for the development of diabetes.

Results: The overall prevalence of GAD autoantibodies was 4.0%, and it varied across racial/ethnic groups from 2.4% among Asian-Pacific Islanders to 7.0% among non-Hispanic black people. There were no significant differences in BMI or metabolic variables (glucose, insulin, HbA(1c), estimated insulin resistance, corrected insulin response) stratified by baseline GAD antibody status. GAD autoantibody positivity did not predict diabetes overall (adjusted hazard ratio 0.98; 95% CI 0.56-1.73) or in any of the three treatment groups. Insulinoma-associated-2 autoantibodies were positive in only one participant (0.033%).

Conclusions: These data suggest that 'diabetes autoimmunity', as reflected by GAD antibodies and insulinoma-associated-2 autoantibodies, in middle-aged individuals at risk for diabetes is not a clinically relevant risk factor for progression to diabetes.

Trial registration: ClinicalTrials.gov NCT00038727.

Publication types

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

MeSH terms

  • Autoantibodies / blood*
  • Autoantibodies / immunology
  • Autoimmunity
  • Blood Glucose / metabolism
  • Diabetes Mellitus / immunology*
  • Diabetes Mellitus / prevention & control
  • Disease Progression
  • Female
  • Follow-Up Studies
  • Glutamate Decarboxylase / immunology*
  • Humans
  • Hypoglycemic Agents / therapeutic use*
  • Insulin / immunology
  • Insulin / metabolism
  • Insulin Resistance* / immunology
  • Insulin Secretion
  • Islets of Langerhans / metabolism*
  • Male
  • Metformin / therapeutic use*
  • Middle Aged
  • Predictive Value of Tests
  • Prevalence
  • Receptor-Like Protein Tyrosine Phosphatases, Class 8 / immunology*
  • Risk Reduction Behavior*
  • Treatment Outcome


  • Autoantibodies
  • Blood Glucose
  • Hypoglycemic Agents
  • Insulin
  • Metformin
  • Receptor-Like Protein Tyrosine Phosphatases, Class 8
  • Glutamate Decarboxylase

Associated data

  • ClinicalTrials.gov/NCT00038727