PHARMACOLOGICAL APPROACHES TO THE PREVENTION OF AUTOIMMUNE DIABETES

Insulin-dependent (type I) diabetes mellitus (IDDM) is the consequence of a chronic cell-mediated immune attack upon the insulin-producing b eta-cells. Progressive insulinopenia is characteristic of individuals who eventually develop IDDM. Autoimmunity develops because of a failur e in self-nonself discrimination. Autoimmunity is usually detected whe n autoantibodies are present in the patient's serum. However, autoanti bodies 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 coul d 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 t esting to identify individuals with 'prediabetes'. The most useful aut oantibodies for prediabetes screening include islet cell autoantibodie s, 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 b enefit 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 vecto rs for gene therapy in the prevention of IDDM.