The Effect of Glucose-dependent Insulinotropic Polypeptide (GIP), Glucagon-like Peptide-1 (GLP-1) and Glucagon-like Peptide-2 (GLP-2) in Individuals With Genetically Altered Receptor Function
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 60
- 试验地点
- 1
- 主要终点
- For GLP-2 receptor variants: CTX (bone resorption marker)
研究概览
简要总结
This project will characterize the physiological effect of the hormones, GIP-, GLP-1- and GLP-2 infusions in a group of individuals that are carriers of GIP-, GLP-1- and GLP-2 receptor gene variants, respectively.
详细描述
Participants with mutations in their GLP-1- and GIP receptor will attend five randomized experimental days, A1, A2, B, C and D. On day A1 an oral glucose tolerance test (OGTT) will be performed, and on day A2, an intravenous isoglycaemic glucose infusion (IIGI) will be performed. On experimental day B and C, the study participants will receive GLP-1 and GIP hormones, respectively, under stable glucose infusions and on experimental day D, they will receive infusion of salt water (placebo) under stable glucose infusion.
Participants with mutations in their GLP-2 receptor will attend three randomized experimental days, E, F and G. A mixed meal test (MMT) will be performed on day E, an infusion with GLP-2 during fasting blood glucose levels will be performed on day F, and infusion with salt water (placebo) during fasting blood glucose levels will be performed on day G.
Additionally, a DXA scan and arginine test will be performed on all study participants.
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
- Single (Participant)
入排标准
- 年龄范围
- 18 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •BMI 19-35 kg/m2
排除标准
- •Treatment with medication or supplements that can not be discontinued for 12 hours
- •>10 objects of alcohol weekly or abuse of narcotics
- •Liver disease (defined as ALAT and/or ASAT ≥ 2 x normal levels)
- •Decreased kidney function (creatine levels over reference interval)
- •Uncontrollable increased blood pressure (> 140/90 mmHg)
- •Low blood percentage (hemoglobin < 8.3 mmol/l)
- •Special diet or planned weight change during trial period
- •Other conditions that could be expected to affect the primary or secondary outcomes
研究组 & 干预措施
GIPR variant carriers
Inidividuals with GIPR variants: Determination of the incretin effect, and the insulinotropic actions of GIP and GLP-1 infusions during hyperglycemic clamp.
干预措施: GIP(1-42) (Drug)
GIPR variant carriers
Inidividuals with GIPR variants: Determination of the incretin effect, and the insulinotropic actions of GIP and GLP-1 infusions during hyperglycemic clamp.
干预措施: Placebo (Other)
GIPR variant carrier controls
Healthy matched individuals: Determination of incretin effect, and the insulinotropic actions of GIP and GLP-1 infusions during hyperglycemic clamp.
干预措施: GIP(1-42) (Drug)
GIPR variant carrier controls
Healthy matched individuals: Determination of incretin effect, and the insulinotropic actions of GIP and GLP-1 infusions during hyperglycemic clamp.
干预措施: Placebo (Other)
GLP-1R variant carrier
Individuals with GLP-1R variants: Determination of incretin effect, and the insulinotropic actions of GIP and GLP-1 infusions during hyperglycemic clamp
干预措施: GIP(1-42) (Drug)
GLP-1R variant carrier
Individuals with GLP-1R variants: Determination of incretin effect, and the insulinotropic actions of GIP and GLP-1 infusions during hyperglycemic clamp
干预措施: Placebo (Other)
GLP-1R variant carrier controls
Healthy matched individuals: Determination of incretin effect, and the insulinotropic actions of to GIP and GLP-1 infusions during hyperglycemic clamp.
干预措施: GIP(1-42) (Drug)
GLP-1R variant carrier controls
Healthy matched individuals: Determination of incretin effect, and the insulinotropic actions of to GIP and GLP-1 infusions during hyperglycemic clamp.
干预措施: Placebo (Other)
GLP-2R variant carrier
Individuals with GLP-2R variants: Determination of bone resorption marker levels (CTX) and response to GLP-2 infusions during fasting blood glucose levels
干预措施: GLP-2 (Drug)
GLP-2R variant carrier
Individuals with GLP-2R variants: Determination of bone resorption marker levels (CTX) and response to GLP-2 infusions during fasting blood glucose levels
干预措施: Placebo (Other)
GLP-2R variant carrier control
Healthy matched individuals: Determination of bone resorption marker levels (CTX) and response to GLP-2 infusions during fasting blood glucose levels
干预措施: GLP-2 (Drug)
GLP-2R variant carrier control
Healthy matched individuals: Determination of bone resorption marker levels (CTX) and response to GLP-2 infusions during fasting blood glucose levels
干预措施: Placebo (Other)
GLP-1R variant carrier
Individuals with GLP-1R variants: Determination of incretin effect, and the insulinotropic actions of GIP and GLP-1 infusions during hyperglycemic clamp
干预措施: GLP-1 (Drug)
GLP-1R variant carrier controls
Healthy matched individuals: Determination of incretin effect, and the insulinotropic actions of to GIP and GLP-1 infusions during hyperglycemic clamp.
干预措施: GLP-1 (Drug)
GIPR variant carrier controls
Healthy matched individuals: Determination of incretin effect, and the insulinotropic actions of GIP and GLP-1 infusions during hyperglycemic clamp.
干预措施: GLP-1 (Drug)
GIPR variant carriers
Inidividuals with GIPR variants: Determination of the incretin effect, and the insulinotropic actions of GIP and GLP-1 infusions during hyperglycemic clamp.
干预措施: GLP-1 (Drug)
结局指标
主要结局
For GLP-2 receptor variants: CTX (bone resorption marker)
时间窗: 120 minutes
Blood sample
For GIP- and GLP-1 receptor variants: Insulinotropic effect (C-peptide)
时间窗: 240 minutes
Blood sample
次要结局
- Glucagon(240 minutes)
- GLP-1 levels(240 minutes)
- Heart rate(240 minutes)
- Insulin(240 minutes)
- GLP-2 levels(240 minutes)
- CTX (bone resorption marker)(240 minutes)
- GIP levels(240 minutes)
- P1NP (bone formation marker)(240 minutes)