The Effect of GIP, GLP-1 and GLP-2 in Individuals With Genetically Altered Receptor Function
- Conditions
- Incretin Effect
- Interventions
- Registration Number
- NCT06194955
- Lead Sponsor
- University of Copenhagen
- Brief Summary
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.
- Detailed Description
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.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 60
- BMI 19-35 kg/m2
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- CROSSOVER
- Arm && Interventions
Group Intervention Description GIPR variant carriers GIP(1-42) Inidividuals with GIPR variants: Determination of the incretin effect, and the insulinotropic actions of GIP and GLP-1 infusions during hyperglycemic clamp. GIPR variant carriers GLP-1 Inidividuals with GIPR variants: Determination of the incretin effect, and the insulinotropic actions of GIP and GLP-1 infusions during hyperglycemic clamp. GIPR variant carriers Placebo Inidividuals with GIPR variants: Determination of the incretin effect, and the insulinotropic actions of GIP and GLP-1 infusions during hyperglycemic clamp. GIPR variant carrier controls GIP(1-42) Healthy matched individuals: Determination of incretin effect, and the insulinotropic actions of GIP and GLP-1 infusions during hyperglycemic clamp. GIPR variant carrier controls GLP-1 Healthy matched individuals: Determination of incretin effect, and the insulinotropic actions of GIP and GLP-1 infusions during hyperglycemic clamp. GIPR variant carrier controls Placebo Healthy matched individuals: Determination of incretin effect, and the insulinotropic actions of GIP and GLP-1 infusions during hyperglycemic clamp. GLP-2R variant carrier control Placebo Healthy matched individuals: Determination of bone resorption marker levels (CTX) and response to GLP-2 infusions during fasting blood glucose levels GLP-1R variant carrier GIP(1-42) Individuals with GLP-1R variants: Determination of incretin effect, and the insulinotropic actions of GIP and GLP-1 infusions during hyperglycemic clamp GLP-1R variant carrier GLP-1 Individuals with GLP-1R variants: Determination of incretin effect, and the insulinotropic actions of GIP and GLP-1 infusions during hyperglycemic clamp GLP-1R variant carrier Placebo Individuals with GLP-1R variants: Determination of incretin effect, and the insulinotropic actions of GIP and GLP-1 infusions during hyperglycemic clamp GLP-1R variant carrier controls GIP(1-42) Healthy matched individuals: Determination of incretin effect, and the insulinotropic actions of to GIP and GLP-1 infusions during hyperglycemic clamp. GLP-1R variant carrier controls Placebo Healthy matched individuals: Determination of incretin effect, and the insulinotropic actions of to GIP and GLP-1 infusions during hyperglycemic clamp. GLP-2R variant carrier GLP-2 Individuals with GLP-2R variants: Determination of bone resorption marker levels (CTX) and response to GLP-2 infusions during fasting blood glucose levels GLP-2R variant carrier Placebo Individuals with GLP-2R variants: Determination of bone resorption marker levels (CTX) and response to GLP-2 infusions during fasting blood glucose levels GLP-2R variant carrier control GLP-2 Healthy matched individuals: Determination of bone resorption marker levels (CTX) and response to GLP-2 infusions during fasting blood glucose levels GLP-1R variant carrier controls GLP-1 Healthy matched individuals: Determination of incretin effect, and the insulinotropic actions of to GIP and GLP-1 infusions during hyperglycemic clamp.
- Primary Outcome Measures
Name Time Method For GIP- and GLP-1 receptor variants: Insulinotropic effect (C-peptide) 240 minutes Blood sample
For GLP-2 receptor variants: CTX (bone resorption marker) 120 minutes Blood sample
- Secondary Outcome Measures
Name Time Method GIP levels 240 minutes Blood sample
GLP-1 levels 240 minutes Blood sample
Heart rate 240 minutes Beats/minute
Insulin 240 minutes Blood sample
Glucagon 240 minutes Blood sample
GLP-2 levels 240 minutes Blood sample
CTX (bone resorption marker) 240 minutes Blood sample
P1NP (bone formation marker) 240 minutes Blood Sample
Trial Locations
- Locations (1)
Center for Clinical Metabolic Research, Gentofte Hospital
🇩🇰Hellerup, Denmark