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Autoantibodies in Diabetes

From the Departments of Pediatrics and Medicine, University of Washington, Seattle, Washington

Islet cell autoantibodies are strongly associated with the development of type 1 diabetes. The appearance of autoantibodies to one or several of the autoantigens—GAD65, IA-2, or insulin—signals an autoimmune pathogenesis of ß-cell killing. A ß-cell attack may be best reflected by the emergence of autoantibodies dependent on the genotype risk factors, isotype, and subtype of the autoantibodies as well as their epitope specificity. It is speculated that progression to ß-cell loss and clinical onset of type 1 diabetes is reflected in a developing pattern of epitope-specific autoantibodies. Although the appearance of autoantibodies does not follow a distinct pattern, the presence of multiple autoantibodies has the highest positive predictive value for type 1 diabetes. In the absence of reliable T-cell tests, dissection of autoantibody responses in subjects of genetic risk should prove useful in identifying triggers of islet autoimmunity by examining seroconversion and maturation of the autoantibody response that may mark time to onset of type 1 diabetes. The complexity of the disease process is exemplified by multiple clinical phenotypes, including autoimmune diabetes masquerading as type 2 diabetes in youth and adults. Autoantibodies may also provide prognostic information in clinically heterogeneous patient populations when examined longitudinally.

Abbreviations: DAA, diabetes autoantibody; DAISY, Diabetes Autoimmunity Study in the Young; DASP, Diabetes Autoantibody Standardization Program; DPT-1, Diabetes Prevention Trial; GAD65Ab, GAD65 autoantibody; IA-2, insulinoma-antigen 2; IA-2Ab, IA-2 autoantibody; IAA, insulin autoantibody; ICA, islet cell antibody; LADA, latent autoimmune diabetes in the adult

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