DIABETES MELLITUS: PATHOGENESIS AND IMMUNE INTERVENTION

本研究项目的总体目标是更好地阐明 与I型胰岛素依赖型糖尿病相关免疫病理学 （胰岛素依赖型糖尿病），并确定免疫干预是否改变胰岛素依赖型糖尿病的进程。 具体目标包括：描述一组患有 在胰岛β细胞功能方面， 免疫参数被认为可能与 胰岛素依赖型糖尿病;胰岛β细胞与胰岛素依赖型糖尿病的关系 功能，各种免疫参数和HLA类型;以及更好地定义 残余胰岛β细胞功能和各种免疫功能的自然史 在IDDM的过程中。 此外，本研究将 确定患者中环孢素免疫干预的效果 近期发病的IDDM患者，包括： IDDM，发病后1年，与安慰剂治疗对照组相比 环孢素免疫干预对免疫功能的影响 糖尿病控制、残余胰岛β细胞功能和免疫参数 认为与胰岛免疫原性相关;相对疗效 免疫干预与环孢素的安全性; 糖尿病微血管病变，特别是糖尿病的外观 视网膜病变和肾功能的变化。 本研究为随机、双盲、安慰剂对照临床试验 评价环孢素在I型糖尿病患者中的作用 胰岛素依赖型糖尿病4周内开始 诊断. 该试验将评估多达100-110名患者，50-55名患者 每次治疗。 患者将被分为三组， 根据随机化时IDDM的严重程度， 初次介绍。 两个治疗类别中的受试者将 根据概述的方案接受强化胰岛素治疗 下面 结果将根据完整的外观来判断 或部分缓解。 残余内源性胰岛β细胞功能，如 通过C肽分泌进行评估，将在一系列 基础 非特异性和胰岛特异性免疫参数 将被连续监测。

The overall objective of this research project is to better clarify the immunopathology associated with Type I insulin dependent diabetes mellitus (IDDM) and to determine if immune intervention alters the course of IDDM. The specific aims include: characterization of a cohort of patients with recent onset IDDM in terms of pancreatic islet beta cell function and immune parameters thought potentially related to the etiopathogenesis of IDDM; definition of the relationship between pancreatic islet beta cell function, various immune parameters, and HLA type; and better definition of the natural history of residual islet beta cell function and various immune parameters during the course of IDDM. In addition, this study will determine the effects of immune intervention with cyclosporine in patients with recent onset IDDM, including: the frequency of complete remission of IDDM, one year after onset, in comparison to a placebo treated control group; the effects of immune intervention with cyclosporine on degree of diabetic control, residual islet beta cell function, and immune parameters thought related to pancreatic islet immunogenicity; the relative efficacy and safety of immune intervention with cyclosporine; the evolution of diabetic microangiopathy, specifically the appearance of diabetic retinopathy and of changes in renal function. The study is a randomized, double-blind, placebo controlled clinical trial evaluating the effects of cyclosporine in patients with Type I Insulin-Dependent Diabetes Mellitus commencing within four weeks of diagnosis. The trial will evaluate up to 100-110 patients, 50-55 patients with each treatment. Patients will be stratified into three groups, prior to randomization, based on the degree of severity of IDDM at the time of initial presentation. Subjects in both treatment categories will be treated with Intensive Insulin Therapy according to the protocol outlined below. Outcome will be judged on the basis of the appearance of complete or partial remissions. Residual endogenous islet beta cell function, as assessed by C-peptide secretion, will be carefully evaluated on a serial basis. Both non-specific and pancreatic islet specific immune parameters will be monitored serially.