CLINICAL AFFILIATE OF THE TYPE 1 DIABETES TRIALNET

描述（由申请人提供）：1型糖尿病（T1D）发生在遗传易感个体中，是胰腺细胞进行性、选择性破坏的结果，主要由自身反应性T细胞介导。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，最常见于儿童、青少年和年轻人。若干年后，这些人面临慢性并发症的风险，这可能会严重削弱身体并危及生命。细胞破坏的过程早在临床疾病发生之前就开始了，并在高血糖发生后继续；在诊断时，通过对混合膳食耐受试验（MMTT）的c肽反应测量，受试者保留了大量的¿-细胞功能。然而，在诊断后，细胞功能继续恶化，随着时间的推移，可能会几乎完全失去分泌。目前还没有完全阻断胰岛自身免疫的治疗方法。然而，临床试验已经显示出有希望的结果，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肽分泌。糖尿病试验网是一个由国际研究人员组成的联盟，由美国国立卫生研究院资助，研究预防或延缓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：发展更好

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.