Abstract
OBJECTIVE: To review prediction of type 1 diabetes mellitus in light of current trials for prevention and novel preclinical therapies. METHODS: The stages in the development of type 1A diabetes are reviewed and strategies for prevention are discussed. RESULTS: From islet autoantibody testing of random cadaveric donors, it is apparent that approximately one-half million persons in the United States express multiple islet autoantibodies and are in the process of developing type 1A (immune-mediated) diabetes. It is now possible to predict not only risk for type 1A diabetes but also the approximate age of diabetes onset in children followed up from birth. In animal models, diabetes can be prevented. Some of the immunologic therapies effective in animal models are able to delay loss of insulin secretion in humans. CONCLUSIONS: None of the therapies studied to date in humans can completely arrest progressive loss of insulin secretion resulting from destruction of islet β cells. Nevertheless, current knowledge of pathogenesis (targeting trimolecular recognition complex: major histocompatibility complex, peptide, T-cell receptor) and natural history combined with newer diagnostic methods allows accurate diagnosis and has stimulated the search for novel safe and effective preventive therapies.