Type 1 diabetes mellitus (T1D) arises from selective immunologically mediated destruction of the insulin-producing beta-cells in the pancreatic islets of Langerhans with consequent insulin deficiency. This occurs in genetically susceptible individuals and is a cellular-mediated process, presumably a specific reaction to one or more beta-cell proteins (autoantigens), although probably initiated by some environmental factor(s). There is consequent progressive impairment of beta-cell function and decline in beta-cell mass. A secondary humoral immune response is characterized by the appearance of autoantibodies that serve as markers of the immune damage to beta-cells. This insidious T1D disease process evolves over a period of years. The decline in beta-cell function and mass is evidenced metabolically by loss of first-phase insulin response to an intravenous glucose challenge, and later by the appearance of impairment in glycemic regulation, manifested as dysglycemia--usually as impaired glucose tolerance, but occasionally as impaired fasting glucose. Ultimately, the clinical syndrome of T1D becomes evident when the majority of beta-cells have been destroyed and frank hyperglycemia supervenes. Given this sequence of events, for which it is possible to envision intervention to interdict the process, it is not surprising that much research effort has been expended to identify individuals at risk of the disease.