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Diabetes 53:384-392, 2004
© 2004 by the American Diabetes Association, Inc.
Stratification of Type 1 Diabetes Risk on the Basis of Islet Autoantibody Characteristics
1 Diabetes Research Institute and 3rd Medical Department, Hospital München-Schwabing, Munich, Germany
2 Diabetes and Metabolism, Division of Medicine, University of Bristol, Bristol, U.K
3 Instituto Scientifico San Raffaele, Milan, Italy
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-2ß. 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.
Address correspondence and reprint requests to Dr. Anette-G. Ziegler, MD, Diabetes Research Institute, Koelner Platz 1, 80804 Munich, Germany. E-mail: anziegler{at}lrz.uni-muenchen.de
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