Journal Article

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

Shalamar Sibley, Michael W. Steffes, William Thomas, Melissa Jackson

2003

Overview

β-Cell Function and the Development of Diabetes-Related Complications in the Diabetes Control and Complications Trial Michael W. Steffes , MD, PHD 1 , Shalamar Sibley , MD, MPH 2 , Melissa Jackson , MPH 3 and William Thomas , PHD 3 1 Department of Laboratory Medicine and Pathology, University of Minnesota Medical School, Minneapolis, Minnesota 2 Department of Medicine, University of Minnesota Medical School, Minneapolis, Minnesota 3 Division of Biostatistics, University of Minnesota School of Public Health, Minneapolis, Minnesota 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 β-cell secretion of insulin. In this retrospective analysis to distinguish the incremental benefits of residual β-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: ≤0.03, 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 >40 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 (∼65% of participants) in the first three groups; however, those subjects with mixed-meal stimulated C-peptide level >0.20 nmol/l for at least baseline and the first annual visit in the DCCT experienced a reduced prevalence of ∼30%. Therefore, even modest levels of β-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). AER, albumin excretion rate DCCT, Diabetes Control and Complications Trial ETDRS, Early Treatment of Diabetic Retinopathy Study HPLC, high-performance liquid chromatography Footnotes Address correspondence and reprint requests to Michael W. Steffes, Department of Laboratory Medicine and Pathology, Mayo Mail Code 609, 420 Delaware St. S.E., Minneapolis, MN 55455. E-mail: steff001{at}umn.edu . Received for publication 7 February 2002 and accepted in revised form 4 December 2002. A table elsewhere in this issue shows conventional and Système International (SI) units and conversion factors for many substances. DIABETES CARE

• Publisher: American Diabetes Association
• Subject: Adult / Associated diseases and complications / Biological and medical sciences / Blood Glucose / C-Peptide - blood / Diabetes Mellitus, Type 1 - complications / Diabetes Mellitus, Type 1 - metabolism / Diabetes Mellitus, Type 1 - therapy / Diabetes. Impaired glucose tolerance / Diabetic Nephropathies - etiology / Diabetic Nephropathies - metabolism / Diabetic Retinopathy - etiology / Diabetic Retinopathy - metabolism / Endocrine pancreas. Apud cells (diseases) / Endocrinopathies / Female / Glycated Hemoglobin A - analysis / Humans / Hypoglycemia - etiology / Hypoglycemia - metabolism / Islets of Langerhans - metabolism / Male / Medical sciences / Pancreatic beta cells / Physiological aspects / Retrospective Studies / Type 1 diabetes