Hyperglycemia Potentiates the Slowing of Gastric Emptying Induced by Exogenous GLP-1

• DOI: 10.2337/dc14-3091
• Publication Date: 2015-03-18T02:33:18Z
• Authors: Mark P. Plummer; Karen L. Jones; Caroline E. Cousins; Laurence G. Trahair; Juris J. Meier; Marianne J. Chapman; Michael Horowitz; Adam M. Deane
• Keywords: Blood Glucose; Male; Infusions; 610; 03 medical and health sciences; gastric emptying; 0302 clinical medicine; Double-Blind Method; Gastrointestinal Agents; Glucagon-Like Peptide 1; Diabetes Mellitus; blood glucose; Humans; Hypoglycemic Agents; Insulin; Infusions, Intravenous; Aged; Analysis of Variance; Middle Aged; Healthy Volunteers; 6. Clean water; 3. Good health; Glucose; Diabetes Mellitus, Type 2; Gastric Emptying; Hyperglycemia; Female; hyperglycemia; Intravenous; Type 2

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.