ORAL INSULIN FOR PREVENTION OF DIABETES IN RELATIVES AT RISK FOR T1D MELLITUS

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 1型糖尿病-T1 DM是一种免疫介导的疾病，其中产生胰岛素的β细胞被破坏，导致对外源性胰岛素的终身依赖，这种依赖每年都在增加，并且在跟踪这一信息的国家中正在接近流行水平。关于1型糖尿病-T1 D疾病过程的自然史已经知道很多。β细胞破坏通常在临床发作前数年开始，如通过疾病相关抗原的循环自身抗体的存在所鉴定的。尽管在临床诊断之前检测到β细胞功能受损，但在诊断时，T1 D患者保留了大量的β细胞功能，如通过对混合餐耐受试验-MMTT的C肽反应所测量的。 受影响的个体通常进入缓解期，其中也可以看到这种胰岛素分泌。 β细胞功能在诊断后恶化，最终变得不可检测，并需要增加对外源性胰岛素替代的依赖。结果表明，口服胰岛素或GAD给药引起的耐受可减弱胰岛自身免疫，导致疾病发作延迟。 在已完成的1型糖尿病预防试验-DPT-1中，口服胰岛素似乎可有效延迟T1 DM患者亲属中存在T1 DM风险的亚组的发病。 本研究的主要目的是确定重组人胰岛素重复口服给药干预是否能预防或延迟有T1 DM风险的受试者发生临床T1 DM。

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.