Effects of Glucagon-Like Peptide-1 (GLP-1) administration on gastric emptying during periods of hyperglycaemia in healthy volunteers.
Effects of exogenous Glucagon-Like Peptide-1 (GLP-1) administration on gastric emptying during hyperglycaemic clamp experiments in healthy volunteers.
Dr Mark Plummer
15 participants
Sep 6, 2013
Interventional
Conditions
Summary
The major mechanism of action of GLP-1 agonists in lowering post-prandial glycaemia is their ability to slow gastric emptying. Acute hyperglycaemia itself is known to slow gastric emptying substantially and it is likely that many patients will be hyperglycaemic at the time of GLP-1 administration. If GLP-1 does not further slow gastric emptying during marked hyperglycaemia then it is likely the agonists will have only a minimal effect to attenuate postprandial glycaemia. The latter observation would support a rationale to reserve GLP-1 agonists until fasting glycaemia is reduced, eg. by initial insulin therapy, whereas if the hypothesis is rejected then GLP-1 agonists would be a rational choice as single agents even in patients with marked fasting hyperglycaemia. Accordingly, it is important to determine whether hyperglycaemia per se affects the capacity for GLP-1 to slow gastric emptying.
Eligibility
Inclusion Criteria1
- healthy volunteers, with no history of diabetes, minimal alcohol and nicotine consumption and BMI <32, aged 50-80 years
Exclusion Criteria15
- Inability to give informed consent
- Known diabetes mellitus or a glycated haemoglobin (HbA1c) >/=6.5%
- Abnormal ferritin levels, haemoglobin levels or liver function on screening
- Previous gastrointestinal surgery
- Taking medications known to affect gastrointestinal motility or blood sugar.
- This includes: insulin, oral hypoglycaemic agents (metformin, sulphonylureas, acarbose), antibiotics, steroids, proton pump inhibitors, amtiemetics, prokinetic agents and H2 receptor antagonists.
- Body Mass Index >32kg/m2
- Smoking >10 cigarettes/day
- Alcohol consumption >20g/day
- Previous exposure to radiation for research purposes in the preceding 12 months
- Volunteers who have donated blood in the preceding 3 months
- Female volunteers of child bearing age who are pregnant or lactating, or who have inadequate contraception
- Suffer from any chronic medical condition such as (but not limited to) heart failure, ischaemic heart disease, chronic lung disease, autonomic dysfunction resulting from any cause, active or previously treatment malignancy, chronic infections (e.g. viral hepatitis and HIV)
- Taking any prescription or over the counter medications other than simple analgesics (e.g. paracetamol)
- Suffered from any acute medical illness (e.g. upper respiratory tract infection, pneumonia...etc) during the 4 week period before recruitment
Interested in this trial?
Get notified about updates and connect with the research team.
Interventions
Each volunteer will be studied on 4 occasions separated by a minimum of 1 week. Each subject will receive intravenous infusions (over 4.5 hours) of (i) GLP-1 at 0.9 pmol/kg/min, or (ii) 0.9% isotonic saline. For both GLP-1 and control, blood glucose will be maintained at either (i) hyperglycaemia (15mmol/l) or (ii) euglycaemia (~6mmol/l) using a glucose infusion clamp.
Locations(1)
View Full Details on ANZCTR
For the most up-to-date information, visit the official listing.
ACTRN12613001384741