Age of Islet Autoantibody Appearance and Mean Levels of Insulin, But Not GAD or IA-2 Autoantibodies, Predict Age of Diagnosis of Type 1 Diabetes

Diabetes Autoimmunity Study in the Young

  1. Marian J. Rewers, MD, PHD
  1. Barbara Davis Center for Childhood Diabetes, University of Colorado Denver (UCD), Aurora, Colorado
  1. Corresponding author: Andrea Steck, andrea.steck{at}
  1. A.K.S. and K.J. contributed equally to this work.


OBJECTIVE We evaluated predictors of progression to diabetes in children with high-risk HLA genotypes and persistent islet autoantibodies.

RESEARCH DESIGN AND METHODS The Diabetes Autoimmunity Study in the Young (DAISY) followed 2,542 children with autoantibodies measured to GAD, IA-2, and insulin.

RESULTS Persistent islet autoantibodies developed in 169 subjects, and 55 of those progressed to diabetes. Children expressing three autoantibodies showed a linear progression to diabetes with 74% cumulative incidence by the 10-year follow-up compared with 70% with two antibodies and 15% with one antibody (P < 0.0001). Both age of appearance of first autoantibody and insulin autoantibody (IAA) levels, but not GAD or IA-2 autoantibodies, were major determinants of the age of diabetes diagnosis (r = 0.79, P < 0.0001).

CONCLUSIONS In the DAISY cohort, 89% of children who progressed to diabetes expressed two or more autoantibodies. Age of diagnosis of diabetes is strongly correlated with age of appearance of first autoantibody and IAA levels.


    • Received November 3, 2010.
    • Accepted March 14, 2011.

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