The stages of type 1A diabetes: 2005.
Type 1A diabetes is a chronic autoimmune disease usually preceded by a long prodrome during which autoantibodies to islet autoantigens are present. These antibodies are directed to a variety of antigens, but the best characterized are glutamic acid decarboxylase-65, insulinoma-associated antigen-2, and insulin. We hypothesize that the natural history of type 1A diabetes can be represented by several stages, starting from genetic susceptibility and ending in complete beta-cell destruction and overt diabetes. Type 1A diabetes probably results from a balance between genetic susceptibility and environmental influences. In both humans and animal models, the major determinants of the disease are genes within the major histocompatibility complex. The next best-characterized susceptibility locus is the insulin gene, the variable nucleotide tandem repeat locus. This gene affects the expression of insulin in the thymus and thus may play a role in the modulation of tolerance to this molecule. In a subset of genetically susceptible individuals, the activation of autoimmunity may be triggered by environmental factors such as viruses and/or diet. However, no conclusive association has been established between type 1A diabetes and specific environmental triggers. In this review, we provide evidence that insulin has a fundamental role in anti-islet autoimmunity.
Gianani
Roberto
R
The Barbara Davis Center for Childhood Diabetes, University of Colorado Health Sciences Center, Denver, CO, USA. roberto.gianani@uchsc.edu
Eisenbarth
George S
GS
D000818:Animals; D001323:Autoantibodies / Q000276:immunology; D001324:Autoantigens / Q000276:immunology; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics / Q000276:immunology* / Q000503:physiopathology* / Q000628:therapy; D006801:Humans; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000276:immunology / Q000378:metabolism / Q000473:pathology
D001323:Autoantibodies; D001324:Autoantigens; D007328:Insulin