Hyperglycaemia potentiates GLP-1 induced slowing of gastric emptying — ASN Events
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  3. Hyperglycaemia potentiates GLP-1 induced slowing of gastric emptying

Hyperglycaemia potentiates GLP-1 induced slowing of gastric emptying (#91)

Mark P Plummer 1 , Karen L Jones 2 , Caroline E Cousins 3 , Laurence G Trahair 2 , Juris J Meier 4 , Marianne J Chapman 1 , Michael Horowitz 2 , Adam M Deane 1
  1. Discipline of Acute Care Medicine, University of Adelaide, Adelaide , South Australia, Australia
  2. Discipline of Medicine, University of Adelaide, Adelaide, South Australia, Australia
  3. Intensive Care Research Unit, Royal Adelaide Hospital, Adelaide, South Australia, Australia
  4. Department of Medicine, Ruhr-University, Bochum, Germany

Background and aims:

Acute administration of glucagon-like peptide-1 (GLP-1) and ‘short acting’ GLP-1 agonists slows gastric emptying which is likely the major mechanism responsible for the reduction in postprandial glycaemic excursions. Glycaemia itself modulates gastric emptying such that emptying is slowed by acute hyperglycaemia. The aim of this study was to determine whether hyperglycaemia potentiates the slowing of gastric emptying induced by GLP-1 administration.

Materials and methods:

Ten healthy subjects (5M:5F, 71±5 y, BMI 26±3 kg/m2), were studied on 4 days in a randomised double-blind fashion. Between T= -15-240 min blood glucose was clamped at hyperglycaemia using an intravenous infusion of 25% dextrose (~12 mmol/L; hyper; on 2 days), or maintained at euglycaemia (~6 mmol/L; eu; on 2 days). On hyperglycaemic and euglycaemic days participants received intravenous GLP-1 (1.2 pmol/kg/min) or placebo from T= -30-240 min. At T= 0 min subjects ingested 100g of minced beef labelled with 20 MBq 99mTechnetium-sulphur-colloid and 3g of 3-O-methyl-glucose (3-OMG), a marker of glucose absorption. Gastric emptying was measured scintigraphically from T=0-240 min and serum 3-OMG taken at regular intervals from T=15-240 min. The areas under the curve for gastric emptying and 3-OMG were analysed using one-way RM-ANOVA with Bonferroni-Holm adjustment. Data are mean ± SE.

Results:

Hyperglycaemia 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 hyperglycaemia, such that gastric emptying was markedly slower when compared to GLP-1 administration during euglycaemia (eu/GLP-1 vs hyper/GLP-1; P <0.01) [Fig. 1]. There was a strong association between 3-OMG absorption and gastric emptying (r = -0.80, P <0.001).

Conclusions:

Acute administration of GLP-1 profoundly slows gastric emptying during hyperglycaemia in excess of the slowing induced by GLP-1 during euglycaemia. This effect is associated with a reduction in glucose absorption. These data imply that GLP-1 agonists may further slow gastric emptying in the setting of pre-prandial hyperglycaemia and thereby mitigate post-prandial glycaemic excursions.

1826-ADS_FIG_CROPPED.jpgFigure 1. Intragastric retention (%) of test meal in participants with blood glucose clamped at hyperglycaemia (12mmol/L) or euglycaemia (~6.0mmol/L) with or without IV GLP-1 (1.2pmol/kg.min). Data are mean (SE).