Stratification of type 1 diabetes risk on the basis of islet autoantibody characteristics

P Achenbach, K Warncke, J Reiter, HE Naserke… - Diabetes, 2004 - Am Diabetes Assoc
P Achenbach, K Warncke, J Reiter, HE Naserke, AJK Williams, PJ Bingley, E Bonifacio
Diabetes, 2004Am Diabetes Assoc
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 …
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.
Am Diabetes Assoc