Stratification of Type 1 Diabetes Risk on the Basis of Islet Autoantibody Characteristics

  1. Peter Achenbach1,
  2. Katharina Warncke1,
  3. Jürgen Reiter1,
  4. Heike E. Naserke1,
  5. Alistair J.K. Williams2,
  6. Polly J. Bingley2,
  7. Ezio Bonifacio13 and
  8. Anette-G. Ziegler1
  1. 1Diabetes Research Institute and 3rd Medical Department, Hospital München-Schwabing, Munich, Germany
  2. 2Diabetes and Metabolism, Division of Medicine, University of Bristol, Bristol, U.K
  3. 3Instituto Scientifico San Raffaele, Milan, Italy
  1. Address correspondence and reprint requests to Dr. Anette-G. Ziegler, MD, Diabetes Research Institute, Koelner Platz 1, 80804 Munich, Germany. E-mail: anziegler{at}


Family history of type 1 diabetes and autoantibodies to the islet antigens insulin (IAA), glutamate decarboxylase (GADA), and the protein tyrosine phosphatase-like protein IA-2 (IA-2A) are strong predictors of type 1 diabetes, but the rate of progression to diabetes in multiple islet autoantibody-positive relatives varies widely. We asked whether detailed characterization of islet autoantibodies that included determination of titer, epitope specificity, and IgG subclass would improve diabetes prediction in a large cohort of autoantibody-positive relatives. The study shows a strong association between risk and high titer, broad antibody responses to IA-2 and insulin. The highest risks were associated with high-titer IA-2A and IAA, IgG2, IgG3, and/or IgG4 subclass of IA-2A and IAA, and antibodies to the IA-2-related molecule IA-2β. Using models based on these antibody characteristics, autoantibody-positive relatives can be classified into groups with risks of diabetes ranging from 7 to 89% within 5 years.


    • Accepted November 5, 2003.
    • Received July 25, 2003.
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