Type 1 diabetes.
Type 1 (insulin-dependent) diabetes occurs worldwide and can appear at any age. The genetic susceptibility is strongly associated with HLA-DQ and DR on chromosome 6, but genetic factors on other chromosomes such as the insulin gene on chromosome 11 and the cytotoxic T-lymphocyte antigen gene on chromosome 2 may modulate disease risk. Numerous studies further support the view that environmental factors are important. Gestational infections may contribute to initiation, whereas later infections may accelerate islet beta-cell autoimmunity. The pathogenesis is strongly related to autoimmunity against the islet beta cells. Markers of autoimmunity include autoantibodies against glutamic acid decarboxylase, insulin, and islet cell antigen-2, a tyrosine phosphatase-like protein. Molecular techniques are used to establish reproducible and precise autoantibody assays, which have been subject to worldwide standardization. The diagnostic sensitivity (40-80%) and specificity (99%) of all three autoantibodies for type 1 diabetes are high, and double or triple positivity among first-degree relatives predicts disease. Combined genetic and antibody testing improved prediction in the general population 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. Islet autoantibodies do not seem to be related to late complications but rather to metabolic control, perhaps because the presence of islet cell autoantibodies marks different residual beta-cell function. Combined genetic and autoantibody screening permit rational approaches to identify subjects for secondary and tertiary intervention trials.
Lernmark
A
A
R.H. Williams Laboratory, University of Washington, 1959 N.E. Pacific St., Room K-165, HSB, Seattle, WA 98195, USA. ake@uwashington.edu
D019411:Clinical Laboratory Techniques; D003922:Diabetes Mellitus, Type 1 / Q000145:classification / Q000175:diagnosis* / Q000209:etiology* / Q000628:therapy; D006801:Humans; D012680:Sensitivity and Specificity