Background: Acute administration of glucagon-like peptide-1 (GLP-1) and ‘short acting’ GLP-1 agonists markedly slow gastric emptying in health and type 2 diabetes, which is likely the major mechanism responsible for the reduction in postprandial glycaemic excursions. Glycaemia itself also modulates gastric emptying, such that emptying is markedly accelerated by hypoglycaemia. The aim of this study was to determine whether GLP-1 attenuates the acceleration of gastric emptying induced by hypoglycaemia.
Materials and methods: Ten healthy subjects (5M:5F, age 69±1.7y, BMI 26±1 kg/m2), were studied on 4 days in a randomised double-blind fashion. Following an overnight fast, blood glucose was stabilised using a glucose/insulin clamp at either hypoglycaemia (hypo; blood glucose 2.6mmol/L) or euglycaemia (eu; 6.0mmol/L) between T=-15 to 45min before clamping at 6.0mmol/L until 180min. During hypoglycaemia and euglycaemia each subject received intravenous GLP-1 (1.2pmolkg/min) or placebo between T=-60 to 180min. At T=0min subjects ingested 100g of minced beef (25g protein, 21g fat, ~270Kcal), labelled with 20MBq 99mTechnetium-sulphur-colloid. Gastric emptying was measured scintigraphically with 1 min images acquired until T=180min. The areas under the curve (AUC) for gastric emptying (T=0-180min) was analysed using one-way RM-ANOVA with Bonferroni-Holm adjusted posthoc tests.
Results: Results are mean ± SE. Gastric emptying was accelerated during hypoglycaemia (hypo/placebo vs eu/placebo; P<0.001), and exogenous GLP-1 markedly slowed gastric emptying during euglycaemia (eu/placebo vs eu/GLP-1; P<0.001). During GLP-1 infusion, gastric emptying was faster during hypoglycaemia than euglycaemia (hypo/GLP-1 vs eu/GLP-1; P<0.008). However, the hypoglycemia-induced acceleration of gastric emptying on placebo was attenuated by GLP-1 (hypo/placebo vs hypo/GLP-1; P<0.008).
Conclusions: In health the acceleration of gastric emptying induced by hypoglycaemia is attenuated by exogenous GLP-1. This observation may be of particular relevance to the counter-regulatory response to hypoglycaemia with the combined use of GLP-1 agonists and basal insulin.