β-Cell Function and the Development of Diabetes-Related Complications in the Diabetes Control and Complications Trial

Abstract

In patients with type 1 diabetes, measurement of connecting peptide (C-peptide), cosecreted with insulin from the islets of Langerhans, permits estimation of remaining ␤-cell secretion of insulin. In this retrospective analysis to distinguish the incremental benefits of residual ␤-cell activity in type 1 diabetes, stimulated (90 min following ingestion of a mixed meal) C-peptide levels at entry in the Diabetes Control and Complications Trial (DCCT) were related to measures of diabetic retinopathy and nephropathy and to incidents of severe hypoglycemia. Based on the analytical sensitivity of the assay (0.03 nmol/l) and study entry criteria, the DCCT subjects were divided into four groups of stimulated C-peptide responses: Յ0.03, 0.04 -0.20, 0.21-0.50 nmol/l at entry, and 0.21-0.50 nmol/l at entry and at least 1 year later (sustained C-peptide secretion). Uniformly in the intensive and partially in the conventional DCCT treatment groups, any C-peptide secretion, but especially at higher and sustained levels of stimulated C-peptide, was associated with reduced incidences of retinopathy (both a single three-step change and a repeated three-step change on the Early Treatment of Diabetic Retinopathy Study [ETDRS] scale at the next 6 month visit) and nephropathy (both albuminuria Ͼ40 mg/24 h once and repeated at the next annual visit). There were also differences in severe hypoglycemia across C-peptide levels in both treatment groups. In the intensively treated cohort there were essentially identical prevalences of severe hypoglycemia (ϳ65% of participants) in the first three groups; however, those subjects with mixed-meal stimulated C-peptide level Ͼ0.20 nmol/l for at least baseline and the first annual visit in the DCCT experienced a reduced prevalence of ϳ30%. Therefore, even modest levels of ␤-cell activity at entry in the DCCT were associated with reduced incidences of retinopathy and nephropathy. Also, continuing C-peptide (insulin) secretion is important in avoiding hypoglycemia (the major complication of intensive diabetic therapy).

Determinants of glucose control in patients with chronic pancreatitis

“…This is consistent with previous studies in patients with type 1 diabetes showing a clear relationship between beta cell function and HbA 1c levels during glucose-lowering treatment [27,28]. The mechanisms underling this association have not been completely clarified yet, but may involve the effects of endogenous insulin on alpha cell function [29][30][31] as well as the direct intra-portal drainage of endogenous insulin vs systemic delivery of exogenously administered insulin [32].…”

Fulminant type 1 diabetes as a high risk group for diabetic microangiopathy—a nationwide 5-year-study in Japan

“…In addition, those responders showed a lower risk of diabetic retinopathy and nephropathy than non-responders. A negative relationship between preserved beta cell function and progression of diabetes complications has also been shown in other studies [20][21][22]. Logistic regression analysis showed that decreased C-peptide secretion was a risk for retinopathy and neuropathy in this study.…”

Four-year metabolic outcome of a randomised controlled CD3-antibody trial in recent-onset type 1 diabetic patients depends on their age and baseline residual beta cell mass

“…This is consistent with the DCCT study in which patients with higher beta cell function had a better glucose control and those with a loss of residual beta cell function an increased risk for severe hypoglycaemia [26,27]. In the young placebo subgroup, virtually all patients progressed within 4 years to a metabolic state with wide variability in FBG and with HbA 1c levels >6.5%, despite increased insulin doses.…”