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.
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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
BASIC_SCIENCE
Masking
DOUBLE
Enrollment
18
Glucose-dependent insulinotropic polypeptide (4 pmol/kg/min) during isoglycemia
glucagon-like peptide-1 (1 pmol/kg/min) during isoglycemia
i.v. NaCl during isoglycemia
Center for Diabetesresearch, Gentofte hospital
Hellerup, Denmark
food intake
How much does the participant eat of from the ad libitum meal, measured in gram
Time frame: 250-280 min
hunger
feeling of hunger measured on a visual analogue scale
Time frame: measured at time 0, 30, 60, 90, 120, 180, 210, 240 min
satiety
feeling of satiety measured on a visual analogue scale
Time frame: measured at time 0, 30, 60, 90, 120, 180, 210, 240 min
Fullness
feeling of fullness measured on a visual analogue scale
Time frame: measured at time 0, 30, 60, 90, 120, 180, 210, 240 min
Prospective food consumption
Prospective food consumption measured on a visual analogue scale
Time frame: measured at time 0, 30, 60, 90, 120, 180, 210, 240 min
resting energy expenditure (REE)
changes in REE measured by a ventilated hood 15 minutes at baseline and 15 minutes at time point 210 min.
Time frame: -15 to 0 min. and 210 to 225 min.
Insulin
changes in insulin measured in serum
Time frame: -30, 0, 15, 30, 45, 60, 90, 120, 150, 180, 210, 240 min
C-peptide level
changes in C-peptide level measured in serum
Time frame: -30, 0, 15, 30, 45, 60, 90, 120, 150, 180, 210, 240 min
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50 g oral glucose tolerance test
i.v infusion of GIP and GLP-1 (4 + 1 pmol/kg/min) during isoglycemia
glucagon levels
changes in glucagon levels measured in plasma
Time frame: -30, 0, 15, 30, 45, 60, 90, 120, 150, 180, 210, 240 min
Cholesterol and FFA
changes in cholesterol (TAG, Total cholesterol and free fatty acid measured in plasma)
Time frame: -30, 0, 30, 60, 90, 120, 180, 240 min
C-terminal cross-linked telopeptide of bone collagen (CTX)
changes in level of CTX measured in plasma
Time frame: -30, 0, 30, 60, 90, 120, 180, 240 min
procollagen type 1 N-terminal propeptide (P1NP)
changes in level of P1NP measured in plasma
Time frame: -30, 0, 30, 60, 90, 120, 180, 240 min