Residual Beta Cell Function in Patients with Long-Term Type 1 Diabetes

描述(由申请人提供)：残留C-肽分泌是内源性胰岛素产生的经典标志，在病程为5-15年的1型糖尿病患者中的临床益处是公认的。然而，这种残留的β细胞功能的持久性及其对糖尿病治疗和糖尿病持续时间更长的并发症的影响尚不清楚。来自DCCT/EDIC队列的58名参与者的初步数据表明，即使在平均30年的糖尿病病程之后，这些参与者中仍有17%在混合膳食耐量测试中释放C-肽。为了更全面地了解这种反应的意义，我们建议研究存活的1,251名DCCT/EDIC参与者的刺激C-肽分泌，目的如下：1)使用现代高灵敏度分析(Roche)确定DCCT/EDIC队列中刺激的C-肽反应(目标1)的持久性，并在一个子集中比较多种分析方法(即罗氏、Tosoh和Mercodia)；2)确定血糖(目标2)和其他临床特征(目标3)对残余β细胞功能的可持续性的作用；3)评估残余C-肽分泌对糖尿病管理参数的益处，如胰岛素剂量需求(目标4)、低血糖、微血管和最终大血管并发症的发展(目标5)。通过这项提案发现的信息将为潜在的临床影响提供重要的见解，从今天促进患者的残余β细胞功能到明天预防患者的并发症，甚至到未来治疗糖尿病患者。

DESCRIPTION (provided by applicant): The clinical benefits of residual C-peptide secretion, a classic marker of endogenous insulin production, in patients with type 1 diabetes of 5-15 years duration are well-established. Yet, the persistence of this residual beta cell function and its effects on diabetes management and complications at even longer durations of diabetes are not understood. Preliminary data from 58 participants in the DCCT/EDIC cohort suggest that even after an average 30 years of diabetes duration, 17% of these participants are still releasing C-peptide during a mixed meal tolerance test. To more fully understand the significance of this response, we propose to investigate stimulated C-peptide secretion in the surviving 1,251 DCCT/EDIC participants with the following objectives: 1) to determine the durability of the stimulated C-peptide response (Aim 1) in the DCCT/EDIC cohort using a modern high-sensitivity assay (Roche), and in a subset to compare multiple assays (i.e., Roche, TOSOH, and Mercodia); 2) to define the role of glycemia (Aim 2) and other clinical characteristics (Aim 3) which contribute to the sustainability of residual beta cell function; and 3) to evaluate the benefits of residual C- peptide secretion on parameters of diabetes management, such as insulin dose requirements (Aim 4), and the development of hypoglycemia, microvascular, and ultimately macrovascular complications (Aim 5). The information uncovered through this proposal will provide critical insights on potential clinical implications from promoting residual beta cell function in our patients today to preventing complications in our patients tomorrow and even to curing patients with diabetes in the future.