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Diabetes Care. 2015 Jun;38(6):1123-9. doi: 10.2337/dc14-3091. Epub 2015 Mar 17.

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

Author information

1
Discipline of Acute Care Medicine, University of Adelaide, Adelaide, Australia Department of Critical Care Services, Royal Adelaide Hospital, Adelaide, Australia mark.plummer@adelaide.edu.au.
2
Discipline of Medicine, University of Adelaide, Adelaide, Australia.
3
Department of Critical Care Services, Royal Adelaide Hospital, Adelaide, Australia.
4
Diabetes Division, St. Josef-Hospital, Ruhr-University Bochum, Bochum, Germany.
5
Discipline of Acute Care Medicine, University of Adelaide, Adelaide, Australia Department of Critical Care Services, Royal Adelaide Hospital, Adelaide, Australia.

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.

PMID:
25784665
DOI:
10.2337/dc14-3091
[Indexed for MEDLINE]

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