The effects of Glucagon-Like Peptide 1 on gastric emptying in healthy volunteers with normal or low blood glucose levels

INTERVENTION: There are two interventions in the trial. The first intervention is intravenous Glucagon‐Like Peptide‐1 (1.2 pmol/kg/min) or placebo (normal saline infused at 1 ml/min). The pharmacy at the Royal Adelaide Hospital randomises the volunteers to product or placebo on each occasion and also conducts the blinding. The second intervention is the glycaemia of the volunteers, being either euglycaemia (target blood glucose concentration of 6.0 mmol/l) or hypoglycaemia (target blood glucose concentration of 2.6 mmol/l). This is achieved through administering an intravenous insulin infusion at previously validated rate plus a simultaneous intravenous 25% glucose infusion titratedf to the target glycaemia. There is no blinding to the glycaemia of the patient. Each patient undergoes 4 different experiments in the trial, being as follows: 1. Euglycaemia and GLP‐1; 2. Euglycaemia and placebo; 3. Hypoglycaemia and GLP‐1; and 4. Hypoglycaemia and placebo. This ensures that each of the four possible combinations of interventions is covered by each participant. As noted earlier, the order of combinations 1 and 2 is randomised, as is the order of combinations 3 and 4. Each study day is separated by a minimum of 4 days. The protocol for the study begins at t = ‐60, when the GLP‐1 / placebo infusion is initiated. The glucose‐insulin clamp is started at t = ‐30 and achieved by t = ‐15. The test meal and drink are consumed at t = 0. If the study is a hypoglycaemic study, the clamp is continued until t = 45, when the target blood glucose concentration is increased back to euglycaemia (6.0 mmol/l). Measurements are taken until the study concludes at t = 180. The standardised test meal is 100 grams of minced beef containing 20 MBq of 99m Technetium‐sulphur‐colloid. This is utilised to enable a gamma camera to measure gastric emptying. The standardised test drink is 150 ml of water containing 3 grams of 3‐O‐methyl‐D‐gluco‐pyranose. This is a glucose analogue that is absorbed across the intestinal wall in the same way as glucose but which is not hepatically metabolised and is renally cleared. Blood concentrations of 3‐O‐methyl‐D‐gluco‐pyranose are used to assess glucose absorption. These are both consumed in all studies at t = 0. CONDITION: Gastric emptying in the context of supraphysiologic Glucagon‐Like Peptide‐1 and hypoglycaemia PRIMARY OUTCOME: Gastric emptying. SECONDARY OUTCOME: Glucose absorption. Glucose. Plasma Glucagon‐Like Peptide‐1 concentration. Plasma Glucose‐dependent Insulinotropic Peptide concentration. Plasma glucagon concentration. INCLUSION CRITERIA: Healthy volunteer between 50 and 80 years of age.