Type I diabetes

Type 1 (insulin-dependent) diabetes occurs worldwide and can appear at any age. The genetic susceptibility is strongly associated with HLA-DQ and DX o n chromosome 6, but genetic factors on other chromosomes such as the insuli n gene on chromosome 11 and the cytotoxic T-lymphocyte antigen gene on chro mosome 2 may modulate disease risk. Numerous studies further support the vi ew that environmental factors are important. Gestational infections may con tribute to initiation, whereas later infections may accelerate islet beta-c ell autoimmunity. The pathogenesis is strongly related to autoimmunity agai nst the islet beta cells. Markers of autoimmunity include autoantibodies ag ainst glutamic acid decarboxylase, insulin, and islet cell antigen-2, a tyr osine phosphatase-like protein. Molecular techniques are used to establish reproducible and precise autoantibody assays, which have been subject to wo rldwide standardization. The diagnostic sensitivity (40-80%) and specificit y (99%) of all three autoantibodies for type 1 diabetes are high, and doubl e or triple positivity among first-degree relatives predicts disease. Combi ned genetic and antibody testing improved prediction in the general populat ion despite the transient nature of these autoantibodies. Classification of diabetes has also been improved by autoantibody testing and may be used in type 2 diabetes to predict secondary failure and insulin requirement. Isle t autoantibodies do not seem to be related to late complications but rather to metabolic control, perhaps because the presence of islet cell autoantib odies marks different residual beta-cell function. Combined genetic and aut oantibody screening permit rational approaches to identify subjects for sec ondary and tertiary intervention trials. (C) 1999 American Association for Clinical Chemistry.