Effect of Glucagon-Like Peptide 1 on Non–Insulin-Mediated Glucose Uptake in the Elderly Patient With Diabetes

Effect of Glucagon-Like Peptide 1 on Non–Insulin-Mediated Glucose Uptake in the Elderly Patient With Diabetes Graydon S. Meneilly , MD 1 , Christopher H.S. McIntosh , PHD 2 , Raymond A. Pederson , PHD 2 , Joel F. Habener , MD 6 7 , Ronald Gingerich , PHD 5 , Josephine M. Egan , MD 4 , Diane T. Finegood , PHD 3 and Dariush Elahi , PHD 4 6 1 Medicine and 2 Physiology, University of British Columbia, Vancouver, Canada 3 School of Kinesiology, Simon Fraser University, Burnaby, Canada 4 Laboratory of Clinical Physiology, Gerontology Research Center, National Institute on Aging, National Institutes of Health, Baltimore, Maryland 5 Linco Research, St. Charles, Missouri 6 Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts 7 Laboratory of Molecular Endocrinology, Howard Hughes Medical Institute, Harvard Medical School, Boston, Massachusetts Abstract An important cause of elevated glucose levels in elderly patients with diabetes is an alteration in non–insulin-mediated glucose uptake (NIMGU). Glucagon-like peptide 1 (GLP-1) is an intestinal insulinotropic hormone. It has been proposed that this hormone also lowers glucose levels by enhancing NIMGU. This study was conducted to determine whether GLP-1 augments NIMGU in elderly patients with diabetes, a group in which NIMGU is known to be impaired. Studies were conducted on 10 elderly patients with type 2 diabetes (aged 75 ± 2 years, BMI 27 ± 1 kg/m 2 ) who underwent paired 240-min glucose clamp studies. In each study, octreotide was infused to suppress endogenous insulin release, and tritiated glucose methodology was used to measure glucose production and disposal rates. For the first 180 min, no glucose was infused. From 180 to 240 min, glucose was increased to 11 mmol/l using the glucose clamp protocol. In the GLP-1 study, GLP-1 was infused from 30 to 240 min. In a subsequent control study, insulin was infused using the glucose clamp protocol from 30 to 240 min to match the insulin levels that occurred during the GLP-1 infusion study. During hyperglycemia, GLP-1 enhanced glucose disposal (control study: 2.52 ± 0.19 mg · kg –1 · min –1 ; GLP-1 study: 2.90 ± 0.17 mg · kg –1 · min –1 ; P < 0.0001). Hepatic glucose output was not different between studies. We conclude that GLP-1 may partially reverse the defect in NIMGU that occurs in elderly patients with diabetes. ANOVA, analysis of variance DPIV, dipeptidyl peptidase IV GLP-1, glucagon-like peptide 1 IMGU, insulin-mediated glucose uptake NI