Obesity, Adiposity, Type 2 Diabetes
Conditions
Keywords
incretin hormones, GIP, GLP-1
Brief summary
We aim to delineate the effects of separate and combined infusion of GIP and GLP-1 on food intake, appetite, bone health and fat metabolism in overweight/obese subjects.
Detailed description
The gut-derived incretin glucagon-like peptide-1 (GLP-1) is a potent regulator of gastric emptying, appetite and food intake in humans whereas its sister incretin hormone, glucose-dependent insulinotropic polypeptide (GIP), does not seem to have independent effects on these variables in humans. Interestingly, recent data from rodents have shown that concomitant activation of the GIP and the GLP-1 receptor may potentiate the satiety-promoting and body weight-reducing effects of GLP-1. Also, evidence suggests that GIP may be an important mediator of bone remodelling and lipid deposition. The effect of simultaneous activation of the GIP and GLP-1 receptors on appetite, food intake, fat metabolism and bone health has not been thoroughly examined in humans. The aim of this study is to delineate the effects of GIP/GLP-1 receptor co-activation on food intake, mechanisms regulating food intake, fat and bone metabolism in obese subjects. Material and methods: The investigators plan to include 18 obese/overweight men without diabetes. The primary endpoint of the study is food intake during continuous intravenous infusions of saline (placebo), GIP, GLP-1 and GIP+GLP-1, respectively. Secondary endpoints includes resting energy expenditure (measured by indirect calorimetry), appetite, satiety and hunger assessments (measured by visual analogue scales), plasma insulin, C-peptide and glucagon secretion, plasma triglycerides, cholesterols, and free fatty acid responses and changes in plasma bone turnover markers.
Interventions
OTHERIIGI+GIP
Glucose-dependent insulinotropic polypeptide (4 pmol/kg/min) during isoglycemia
OTHERIIGI+GLP-1
glucagon-like peptide-1 (1 pmol/kg/min) during isoglycemia
OTHERIIGI+NaCl (placebo)
i.v. NaCl during isoglycemia
OTHEROGTT
50 g oral glucose tolerance test
OTHERIIGI+GIP+GLP-1
i.v infusion of GIP and GLP-1 (4 + 1 pmol/kg/min) during isoglycemia
Sponsors
University Hospital, Gentofte, Copenhagen
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
BASIC_SCIENCE
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
MALE
Age
25 Years to 70 Years
Healthy volunteers
Yes
Inclusion criteria
* Caucasian men * Age between 25 and 70 years * Body mass index (BMI) between 25 and 40 kg/m2
Exclusion criteria
* Diabetes or prediabetes (defined as glycated haemoglobin (HbA1c) ≥ 43 mmol/mol) * Anaemia (defined as haemoglobin \< 8.3 mmol/l) * Any gastrointestinal disease that may interfere with the endpoint variables * Anorexia, bulimia or binge eating disorder * Allergy or intolerance to ingredients included in the standardised meals * Tobacco smoking * Any regular drug treatment that cannot be discontinued for minimum 18 hours * Any physical or psychological condition that the investigator feels would interfere with trial participation
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| food intake | 250-280 min | How much does the participant eat of from the ad libitum meal, measured in gram |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| satiety | measured at time 0, 30, 60, 90, 120, 180, 210, 240 min | feeling of satiety measured on a visual analogue scale |
| Fullness | measured at time 0, 30, 60, 90, 120, 180, 210, 240 min | feeling of fullness measured on a visual analogue scale |
| Prospective food consumption | measured at time 0, 30, 60, 90, 120, 180, 210, 240 min | Prospective food consumption measured on a visual analogue scale |
| resting energy expenditure (REE) | -15 to 0 min. and 210 to 225 min. | changes in REE measured by a ventilated hood 15 minutes at baseline and 15 minutes at time point 210 min. |
| Insulin | -30, 0, 15, 30, 45, 60, 90, 120, 150, 180, 210, 240 min | changes in insulin measured in serum |
| hunger | measured at time 0, 30, 60, 90, 120, 180, 210, 240 min | feeling of hunger measured on a visual analogue scale |
| glucagon levels | -30, 0, 15, 30, 45, 60, 90, 120, 150, 180, 210, 240 min | changes in glucagon levels measured in plasma |
| Cholesterol and FFA | -30, 0, 30, 60, 90, 120, 180, 240 min | changes in cholesterol (TAG, Total cholesterol and free fatty acid measured in plasma) |
| C-terminal cross-linked telopeptide of bone collagen (CTX) | -30, 0, 30, 60, 90, 120, 180, 240 min | changes in level of CTX measured in plasma |
| procollagen type 1 N-terminal propeptide (P1NP) | -30, 0, 30, 60, 90, 120, 180, 240 min | changes in level of P1NP measured in plasma |
| C-peptide level | -30, 0, 15, 30, 45, 60, 90, 120, 150, 180, 210, 240 min | changes in C-peptide level measured in serum |
Countries
Denmark
Outcome results
None listed