title: 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.
  
  
  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.affiliation: 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.
authors.forename: Mark P
authors.initials: MP
authors.lastname: Plummer
authors.affiliation: Discipline of Medicine, University of Adelaide, Adelaide, Australia.
authors.forename: Karen L
authors.initials: KL
authors.lastname: Jones
authors.affiliation: Department of Critical Care Services, Royal Adelaide Hospital, Adelaide, Australia.
authors.forename: Caroline E
authors.initials: CE
authors.lastname: Cousins
authors.affiliation: Discipline of Medicine, University of Adelaide, Adelaide, Australia.
authors.forename: Laurence G
authors.initials: LG
authors.lastname: Trahair
authors.affiliation: Diabetes Division, St. Josef-Hospital, Ruhr-University Bochum, Bochum, Germany.
authors.forename: Juris J
authors.initials: JJ
authors.lastname: Meier
authors.affiliation: Discipline of Acute Care Medicine, University of Adelaide, Adelaide, Australia Department of Critical Care Services, Royal Adelaide Hospital, Adelaide, Australia.
authors.forename: Marianne J
authors.initials: MJ
authors.lastname: Chapman
authors.affiliation: Discipline of Medicine, University of Adelaide, Adelaide, Australia.
authors.forename: Michael
authors.initials: M
authors.lastname: Horowitz
authors.affiliation: Discipline of Acute Care Medicine, University of Adelaide, Adelaide, Australia Department of Critical Care Services, Royal Adelaide Hospital, Adelaide, Australia.
authors.forename: Adam M
authors.initials: AM
authors.lastname: Deane
mesh_terms: D000368:Aged; D000704:Analysis of Variance; D001786:Blood Glucose / Q000187:drug effects; D003924:Diabetes Mellitus, Type 2 / Q000503:physiopathology; D004311:Double-Blind Method; D005260:Female; D005746:Gastric Emptying / Q000187:drug effects*; D005765:Gastrointestinal Agents / Q000494:pharmacology*; D052216:Glucagon-Like Peptide 1 / Q000494:pharmacology*; D005947:Glucose / Q000494:pharmacology; D064368:Healthy Volunteers; D006801:Humans; D006943:Hyperglycemia / Q000503:physiopathology*; D007004:Hypoglycemic Agents / Q000494:pharmacology; D007262:Infusions, Intravenous; D007328:Insulin / Q000494:pharmacology; D008297:Male; D008875:Middle Aged
chemical_list: D001786:Blood Glucose; D005765:Gastrointestinal Agents; D007004:Hypoglycemic Agents; D007328:Insulin; D052216:Glucagon-Like Peptide 1; D005947:Glucose