Insulin-dependent (Type 1) diabetes mellitus (IDDM) is a multifactorial autoimmune disease 1 for which susceptibility 2 is determined by genetic, environmental and immunological factors. A number of studies have shown that the islet destructive process is specifically directed against -cells, 3 can last for years before the appearance of clinical symptoms and is characterized by the presence of circulating autoantibodies and T-lymphocytes directed towards islet molecules. 4,5 The information currently available on the pathogenic process of this disease has clearly indicated (at least in animal models such as the NOD mouse or the BB rat) that the progressive autoimmune islet -cell destruction is a T-lymphocyte-mediated event. However, despite the pathogenic importance of the T-cell response in IDDM pathogenesis, the target molecules and the regulation of such a response remain largely uncharacterized, especially in humans.
Although the pathogenic mechanisms have not been elucidated, the prediction of IDDM is now feasible, at least in categories of individuals at increased diabetes risk (e.g., relatives of Type 1 diabetic patients); this has allowed for the possibility to start preventive trials in a window of time of the natural history of the disease where a successful diabetes prevention may be possible. The "predictive tool" is represented by a number of autoantibodies which, although not directly pathogenic, have been shown in prospective studies to be highly associated with future disease development in subjects such as first-degree relatives of Type 1