This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Type 1 diabetes mellitus-T1DM is an immune-mediated disease in which insulin-producing beta cells are destroyed resulting in life-long dependence on exogenous insulin, which is increasing each year and is approaching an epidemic level in countries that track this information. Much is known about the natural history of the type 1 diabetes-T1D disease process. Beta cell destruction generally begins years before clinical onset as identified by the presence of circulating autoantibodies for disease relevant antigens. Though impairment in beta cell function is detected prior to clinical diagnosis, at the time of diagnosis, patients with T1D retain a significant amount of beta cell function as measured by C-peptide responses to a mixed meal tolerance test-MMTT. Affected individuals often enter a remission phase where this insulin secretion is also seen. Beta cell function deteriorates after diagnosis, eventually becoming undetectable and necessitating increasing reliance on exogenous insulin replacement. The results suggest that tolerance provoked by oral insulin or GAD administration can attenuate pancreatic islet autoimmunity, leading to a delay in the onset of the disease. In the completed Type 1 Diabetes Prevention Trial-DPT-1, oral insulin appeared to be effective in delaying the onset of T1DM in a subset of relatives at-risk for the disease. The primary objective of this study is to determine whether intervention with repeated oral administration of recombinant human insulin will prevent or delay development of clinical T1DM in subjects at risk for T1DM.
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