CLINICAL AFFILIATE OF THE TYPE 1 DIABETES TRIALNET

描述(申请人提供)：1型糖尿病(T1D)发生在遗传易感性个体中，其结果是胰腺细胞的进行性、选择性破坏，这主要是由自身反应性T细胞介导的。疾病过程导致胰岛素分泌丧失和终生胰岛素依赖，不幸的是，最常发生在儿童、青少年和年轻人。几年后，这些人面临患上慢性并发症的风险，这可能会严重削弱身体并危及生命。细胞破坏的过程在临床发病前很久就开始了，并在出现高血糖后继续；在诊断时，受试者保留了相当数量的细胞功能，通过对混合餐耐量试验(MMTT)的C肽反应来衡量。然而，细胞功能在确诊后继续恶化，推测随着时间的推移，分泌物几乎完全丧失。目前还没有完全阻断胰岛自身免疫的治疗方法。然而，临床试验显示了有希望的结果，表明有可能干扰胰岛自身免疫，并至少在一段时间内保持C-肽的分泌。糖尿病试验网络是一个由美国国立卫生研究院资助的国际研究人员联盟，研究预防或延迟1型糖尿病的干预措施。作为TrialNet临床中心，我们的长期科学目标是为TrialNet的总体目标做出贡献：开发更好的 了解T1D的自然历史和分子基础，并实施临床试验，评估预防这种疾病的新策略。作为追求这些目标的一步，这项提议的目标是继续积极参与研究网络--1型糖尿病试验网络，并积极参与设计和实施新的预防策略。为调节导致T1D的破坏性过程而采取的每一项研究步骤，都会使我们更接近预防的最终目标。

DESCRIPTION (provided by applicant): Type 1 diabetes (T1D) occurs in genetically predisposed individuals as a result of the progressive, selective destruction of pancreatic ¿-cells, which is primarily mediated by autoreactive T cells. The disease process results in loss of insulin secretion and life-long insulin-dependence, and unfortunately, most often occurs in children, adolescents, and young adults. Years later, these individuals are at risk of developing chronic complications, which can be severely debilitating and life-threatening. The process of ¿-cell destruction begins long before clinical disease onset and continues after development of hyperglycemia; at the time of diagnosis subjects retain a significant amount of ¿-cell function as measured by C-peptide responses to a mixed meal tolerance test (MMTT). However, ¿-cell function continues to deteriorate after diagnosis with the presumed eventuality of near complete loss of secretion over time. At present there is no treatment that fully interdicts islet autoimmunity. However, clinical trials have shown promising results, demonstrating that it is possible to interfere with islet autoimmunity and preserve C-peptide secretion for at least some time. Diabetes TrialNet is a consortium of international researchers, NIH-funded, investigating interventions for the prevention or delay of type 1 diabetes. As a TrialNet Clinical Center our long-term scientific goals are to contribute to the overarching goals of TrialNet: develop a better understanding of the natural history and molecular basis of T1D and implement clinical trials evaluating new strategies to prevent this disease. The objective of this proposal, a step in pursuit of these goals, is to remain an active participant in the research network, Type 1 diabetes TrialNet, and in the process of designing and implementing new prevention strategies. Each investigative step taken toward modulating the destructive process that leads to T1D moves us closer to the ultimate goal of prevention.