GIP/GLP-1 Co-Activity in Subjects With Obesity: Lowering of Food Intake
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 发起方
- 入组人数
- 18
- 试验地点
- 2
- 主要终点
- food intake
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Basic Science
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 25 Years 至 70 Years（Adult, Older Adult）
- 性别
- Male
- 接受健康志愿者
- 是
入选标准
- •Caucasian men
- •Age between 25 and 70 years
- •Body mass index (BMI) between 25 and 40 kg/m2
排除标准
- •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
研究组 & 干预措施
IIGI+GLP-1
4 hour i.v. infusion of glucagon-like peptide-1 (1 pmol/kg/min) during isoglycemic conditions
干预措施: OGTT (Other)
IIGI+GLP-1
4 hour i.v. infusion of glucagon-like peptide-1 (1 pmol/kg/min) during isoglycemic conditions
干预措施: IIGI+GLP-1 (Other)
IIGI+GLP-1
4 hour i.v. infusion of glucagon-like peptide-1 (1 pmol/kg/min) during isoglycemic conditions
干预措施: IIGI+NaCl (placebo) (Other)
IIGI+GIP
4 hour i.v. infusion of glucose-dependent insulinotropic polypeptide (4 pmol/kg/min) during isoglycemic conditions
干预措施: IIGI+GIP+GLP-1 (Other)
IIGI+GLP-1
4 hour i.v. infusion of glucagon-like peptide-1 (1 pmol/kg/min) during isoglycemic conditions
干预措施: IIGI+GIP (Other)
IIGI+GIP
4 hour i.v. infusion of glucose-dependent insulinotropic polypeptide (4 pmol/kg/min) during isoglycemic conditions
干预措施: IIGI+GIP (Other)
IIGI+GIP
4 hour i.v. infusion of glucose-dependent insulinotropic polypeptide (4 pmol/kg/min) during isoglycemic conditions
干预措施: IIGI+GLP-1 (Other)
IIGI+GIP
4 hour i.v. infusion of glucose-dependent insulinotropic polypeptide (4 pmol/kg/min) during isoglycemic conditions
干预措施: IIGI+NaCl (placebo) (Other)
IIGI+GIP
4 hour i.v. infusion of glucose-dependent insulinotropic polypeptide (4 pmol/kg/min) during isoglycemic conditions
干预措施: OGTT (Other)
IIGI+GLP-1
4 hour i.v. infusion of glucagon-like peptide-1 (1 pmol/kg/min) during isoglycemic conditions
干预措施: IIGI+GIP+GLP-1 (Other)
IIGI+NaCl (placebo)
4 hour i.v. NaCl (placebo) during isoglycemic conditions
干预措施: IIGI+GIP (Other)
IIGI+NaCl (placebo)
4 hour i.v. NaCl (placebo) during isoglycemic conditions
干预措施: IIGI+GLP-1 (Other)
IIGI+NaCl (placebo)
4 hour i.v. NaCl (placebo) during isoglycemic conditions
干预措施: IIGI+NaCl (placebo) (Other)
IIGI+NaCl (placebo)
4 hour i.v. NaCl (placebo) during isoglycemic conditions
干预措施: OGTT (Other)
IIGI+NaCl (placebo)
4 hour i.v. NaCl (placebo) during isoglycemic conditions
干预措施: IIGI+GIP+GLP-1 (Other)
IIGI+GIP+GLP-1
4 hour co-infusion of glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1
干预措施: IIGI+GIP (Other)
IIGI+GIP+GLP-1
4 hour co-infusion of glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1
干预措施: IIGI+GLP-1 (Other)
IIGI+GIP+GLP-1
4 hour co-infusion of glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1
干预措施: IIGI+NaCl (placebo) (Other)
IIGI+GIP+GLP-1
4 hour co-infusion of glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1
干预措施: OGTT (Other)
IIGI+GIP+GLP-1
4 hour co-infusion of glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1
干预措施: IIGI+GIP+GLP-1 (Other)
50 g OGTT
50 g oral glucose tolerance test (OGTT)
干预措施: IIGI+GIP (Other)
50 g OGTT
50 g oral glucose tolerance test (OGTT)
干预措施: IIGI+GLP-1 (Other)
50 g OGTT
50 g oral glucose tolerance test (OGTT)
干预措施: IIGI+NaCl (placebo) (Other)
50 g OGTT
50 g oral glucose tolerance test (OGTT)
干预措施: OGTT (Other)
50 g OGTT
50 g oral glucose tolerance test (OGTT)
干预措施: IIGI+GIP+GLP-1 (Other)
结局指标
主要结局
food intake
时间窗: 250-280 min
How much does the participant eat of from the ad libitum meal, measured in gram
次要结局
- hunger(measured at time 0, 30, 60, 90, 120, 180, 210, 240 min)
- Fullness(measured at time 0, 30, 60, 90, 120, 180, 210, 240 min)
- satiety(measured at time 0, 30, 60, 90, 120, 180, 210, 240 min)
- Prospective food consumption(measured at time 0, 30, 60, 90, 120, 180, 210, 240 min)
- resting energy expenditure (REE)(-15 to 0 min. and 210 to 225 min.)
- Insulin(-30, 0, 15, 30, 45, 60, 90, 120, 150, 180, 210, 240 min)
- C-peptide level(-30, 0, 15, 30, 45, 60, 90, 120, 150, 180, 210, 240 min)
- Cholesterol and FFA(-30, 0, 30, 60, 90, 120, 180, 240 min)
- C-terminal cross-linked telopeptide of bone collagen (CTX)(-30, 0, 30, 60, 90, 120, 180, 240 min)
- procollagen type 1 N-terminal propeptide (P1NP)(-30, 0, 30, 60, 90, 120, 180, 240 min)
- glucagon levels(-30, 0, 15, 30, 45, 60, 90, 120, 150, 180, 210, 240 min)
研究者
Natasha Chidekel Bergmann
MD Ph.D student
University Hospital, Gentofte, Copenhagen