Hyperglycemia potentiates the slowing of gastric emptying induced by exogenous GLP-1.

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.

• Authors: Mark P Plummer, Karen L Jones, Caroline E Cousins, Laurence G Trahair, Juris J Meier, Marianne J Chapman, Michael Horowitz, Adam M Deane
• Journal: Diabetes care (Diabetes Care) Vol. 38 Issue 6 Pg. 1123-9 (Jun 2015) ISSN: 1935-5548 [Electronic] United States
• PMID: 25784665 (Publication Type: Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: © 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.

Chemical References

• Blood Glucose
• Gastrointestinal Agents
• Hypoglycemic Agents
• Insulin
• Glucagon-Like Peptide 1
• Glucose

Topics

• Aged
• Analysis of Variance
• Blood Glucose (drug effects)
• Diabetes Mellitus, Type 2 (physiopathology)
• Double-Blind Method
• Female
• Gastric Emptying (drug effects)
• Gastrointestinal Agents (pharmacology)
• Glucagon-Like Peptide 1 (pharmacology)
• Glucose (pharmacology)
• Healthy Volunteers
• Humans
• Hyperglycemia (physiopathology)
• Hypoglycemic Agents (pharmacology)
• Infusions, Intravenous
• Insulin (pharmacology)
• Male
• Middle Aged