Pharmacological approaches to the prevention of autoimmune diabetes.

Abstract

Insulin-dependent (type I) diabetes mellitus (IDDM) is the consequence of a chronic cell-mediated immune attack upon the insulin-producing beta-cells. Progressive insulinopenia is characteristic of individuals who eventually develop IDDM. Autoimmunity develops because of a failure in self-nonself discrimination. Autoimmunity is usually detected when autoantibodies are present in the patient's serum. However, autoantibodies are not synonymous with disease, as many autoantibody-positive individuals show no evidence of clinical disease. Studies initiated in the early 1980s demonstrated that short term remission from IDDM could be induced or lengthened with immunosuppressive therapy. However, no long term remissions were achieved. Current prevention strategies use a combination of autoantibody marker testing and beta-cell function testing to identify individuals with 'prediabetes'. The most useful autoantibodies for prediabetes screening include islet cell autoantibodies, insulin autoantibodies, glutamic acid decarboxylase autoantibodies and IA-2 autoantibodies. Immunointervention techniques have focused on protecting beta-cells from oxidative damage and developing tolerance to beta-cell autoantigens. Environmental manipulation may also be of benefit but its effectiveness is unproven. The pharmacist of the future may be involved in dispensing autoantigens, cytokines, anti-cytokine antibodies, anti-cytokine receptor antibodies, vaccines or viral vectors for gene therapy in the prevention of IDDM.