Incretin Effect
Conditions
Keywords
Gut hormones, single nucleotide variants (SNVs), GIP, GLP-1, GLP-2
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.
Sponsors
Gentofte Hospital, Denmark
University of Copenhagen
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
BASIC_SCIENCE
Masking
SINGLE (Subject)
Intervention model description
Single-blind, randomized, crossover study
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
Yes
Inclusion criteria
* BMI 19-35 kg/m2
Exclusion criteria
* 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| GLP-2 levels | 240 minutes | Blood sample |
| CTX (bone resorption marker) | 240 minutes | Blood sample |
| P1NP (bone formation marker) | 240 minutes | Blood Sample |
| GIP levels | 240 minutes | Blood sample |
| Insulin | 240 minutes | Blood sample |
| Glucagon | 240 minutes | Blood sample |
| Heart rate | 240 minutes | Beats/minute |
| GLP-1 levels | 240 minutes | Blood sample |
Countries
Denmark
Contacts
Primary ContactLærke S Gasbjerg, MD, PhD
Backup ContactSheyma Kizilkaya, MSc
Outcome results
None listed