Hypothesis for the pathogenesis of type 1A diabetes

Type 1A (immune-mediated) diabetes results from T-cell-mediated specific destruction of the islet beta cells that produce insulin (1). One can divide the development of diabetes into a series of overlapping stages beginning with genetic susceptibility and ending with complete beta cell destruction (2). The dominant genetic susceptibility locus is the major histocompatibility complex (MHC), also called the human leukocyte antigen (HLA) region in humans, and in particular, immune response genes DR and DQ (3). Additionally, the existence of a series of rare but informative "single-gene" disorders associated with autoimmune diabetes indicates that a number of different immunologic lesions can lead to autoimmune diabetes. The most common forms of type 1A diabetes are polygenic (multifactorial) disorders with unidentified environmental factors contributing to the disease. Given current information, it is now possible to predict the development of type 1A diabetes (4, 5), and major efforts are under way to create preventive therapies.