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.
The DCCT/EDIC cohort with all the prospectively gathered data presents a unique opportunity to determine the prevalence of residual beta-cell function in long-established type 1 diabetes and to elucidate its effects on longevity and health outcomes. We plan to complete this work with a well-documented MMTT protocol and 3 different assays of C-peptide. Thus, our conclusions may be applied widely in other research venues and likely in the evaluation of patients.