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https://hdl.handle.net/2440/95991
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Type: | Journal article |
Title: | Hyperglycemia potentiates the slowing of gastric emptying induced by exogenous GLP-1 |
Author: | Plummer, M. Jones, K. Cousins, C. Trahair, L. Meier, J. Chapman, M. Horowitz, M. Deane, A. |
Citation: | Diabetes Care, 2015; 38(6):1123-1129 |
Publisher: | American Diabetes Association |
Issue Date: | 2015 |
ISSN: | 0149-5992 1935-5548 |
Statement of Responsibility: | Mark P. Plummer, Karen L. Jones, Caroline E. Cousins, Laurence G. Trahair, Juris J. Meier, Marianne J. Chapman, Michael Horowitz and Adam M. Deane |
Abstract: | OBJECTIVE: Acute hyperglycemia markedly slows gastric emptying. Exogenous GLP-1 also slows gastric emptying, leading to diminished glycemic excursions. The primary objective was to determine whether hyperglycemia potentiates the slowing of gastric emptying induced by GLP-1 administration. RESEARCH DESIGN AND METHODS: Ten healthy participants were studied on 4 separate days. Blood glucose was clamped at hyperglycemia using an intravenous infusion of 25% dextrose (∼12 mmol/L; hyper) on 2 days, or maintained at euglycemia (∼6 mmol/L; eu) on 2 days, between t = -15 and 240 min. During hyperglycemic and euglycemic days, participants received intravenous GLP-1 (1.2 pmol/kg/min) and placebo in a randomized double-blind fashion. At t = 0 min, subjects ingested 100 g beef mince labeled with 20 MBq technetium-99m-sulfur colloid and 3 g 3-O-methyl-glucose (3-OMG), a marker of glucose absorption. Gastric emptying was measured scintigraphically from t = 0 to 240 min and serum 3-OMG taken at regular intervals from t = 15 to 240 min. The areas under the curve for gastric emptying and 3-OMG were analyzed using one-way repeated-measures ANOVA with Bonferroni-Holm adjusted post hoc tests. RESULTS: Hyperglycemia slowed gastric emptying (eu/placebo vs. hyper/placebo; P < 0.001) as did GLP-1 (eu/placebo vs. eu/GLP-1; P < 0.001). There was an additive effect of GLP-1 and hyperglycemia, such that gastric emptying was markedly slower compared with GLP-1 administration during euglycemia (eu/GLP-1 vs. hyper/GLP-1; P < 0.01). CONCLUSIONS: Acute administration of exogenous GLP-1 profoundly slows gastric emptying during hyperglycemia in excess of the slowing induced by GLP-1 during euglycemia. Studies are required to determine the effects of hyperglycemia on gastric emptying with the subcutaneously administered commercially available GLP-1 agonists in patients with type 2 diabetes. |
Keywords: | Humans Diabetes Mellitus, Type 2 Hyperglycemia Insulin Glucose Blood Glucose Gastrointestinal Agents Hypoglycemic Agents Infusions, Intravenous Analysis of Variance Double-Blind Method Gastric Emptying Aged Middle Aged Female Male Glucagon-Like Peptide 1 Healthy Volunteers |
Rights: | © 2015 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. |
DOI: | 10.2337/dc14-3091 |
Grant ID: | http://purl.org/au-research/grants/nhmrc/627011 |
Published version: | http://dx.doi.org/10.2337/dc14-3091 |
Appears in Collections: | Aurora harvest 7 Medicine publications |
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