Autoimmunity in Insulin-Dependent Diabetes Mellitus: Implications For Prediction and Therapy

Insulin-dependent diabetes mellitus (IDDM) is an autoimmune disease, where the insulin-producing β-cells in the pancreatic islets are selectively destroyed. Clinically, symptoms appear abruptly in the majority of new cases of IDDM, but, despite this, there is a prolonged period of latency that precedes, sometimes for several years, the acute onset of the disease. Environmental factors have repeatedly been postulated to initiate and/or precipitate β-cell damage, but their ultimate identification remains still elusive. Recent years have witnessed major advances in the characterisation of novel autoantigens in IDDM, but it is unclear why, apart from insulin, those so far characterised are not strictly β-cell—specific. Although β-cell destruction is believed to be mediated by autoreactive T lymphocytes rather than immunoglobulins, investigations of islet-related autoantibodies, and possibly antibodies to certain exogenous antigens, are relevant for identifying individuals at risk for developing the disease. However, other markers, such as: (a) human leucocyte antigen (HLA) genetic determinants; (b) parameters of cell-mediated immunity; and (c) metabolic tests, such as the intravenous glucose tolerance test where loss of the first-phase insulin secretion is monitored, are also of value in prediction. Improving accurate prediction of the disease remains the ultimate goal for a targeted and safe prevention of IDDM.