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

描述（由申请方提供）：在5-15年持续时间的1型糖尿病患者中，残余C肽分泌（内源性胰岛素产生的经典标志物）的临床获益已得到充分证实。然而，这种残余β细胞功能的持续性及其对糖尿病管理和糖尿病并发症的影响甚至更长的糖尿病持续时间尚不清楚。DCCT/EDIC队列中58名参与者的初步数据表明，即使在平均30年的糖尿病病程后，这些参与者中仍有17%在混合餐耐受性测试中释放C肽。为了更充分地理解这种应答的意义，我们提出在存活的1，251名DCCT/EDIC参与者中研究受刺激的C肽分泌，目的如下：1）使用现代高灵敏度测定（Roche）确定DCCT/EDIC队列中受刺激的C肽应答（Aim 1）的持久性，并在一个子集中比较多种测定（即，Roche、TOSOH和Mercodia）; 2）确定β细胞功能的作用（目标2）和其他临床特征（目标3），这些特征有助于残余β细胞功能的可持续性;和3）评估残余C肽分泌对糖尿病管理参数的益处，例如胰岛素剂量需求（目的4），以及低血糖，微血管，最终导致大血管并发症（目标5）。通过这项提案发现的信息将为潜在的临床意义提供重要的见解，从促进今天患者的残余β细胞功能到预防明天患者的并发症，甚至治愈未来的糖尿病患者。

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.