Endocrine or Metabolic Disease, Glucose Metabolism Disorders
Conditions
Keywords
GLP-2, Glucagon
Brief summary
Infusion of glucagon-like peptide 2 (GLP-2) during euglycaemia, hypoglycaemia and hyperglycaemia and evaluation of the effect on glucagon secretion in healthy subjects.
Detailed description
This is a cross-over, randomized, double-blinded study in which 10 participants will undergo 6 experimental days each. The participants will have their plasma glucose clamped at either euglycaemia (fasting level), hypoglycemia (2,5 mmol/l) or hyperglycemia (10 mmol/l) during infusion of GLP-2 or saline (placebo) The six days will be as follows: * Euglycaemia + Placebo * Euglycaemia + GLP-2 * Hyperglycaemia + Placebo * Hyperglycaemia + GLP-2 * Hypoglycaemia + Placebo * Hypoglycaemia + GLP-2 The primary endpoint will be levels of plasma glucagon. Secondary endpoint will be levels of GLP-1, GLP-2, Insulin/C-peptide, OXM, Amino acids, CCK, Gastrin, norepinephrine, bile acids, FGF-19/FGF-21. Secondary endpoints will also include ultrasound scan of the gallbladder.
Interventions
Human glucagon-like peptide 2
OTHERSaline
Placebo
OTHERGlucose
20% (w/v) glucose infusion for regulating plasma glucose
OTHERInsulin
Actrapid (insulin) for lowering plasma glucose
Sponsors
University Hospital, Gentofte, Copenhagen
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
BASIC_SCIENCE
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
MALE
Age
18 Years to 40 Years
Healthy volunteers
Yes
Inclusion criteria
* Caucasian ethnicity * Body mass index (BMI): 18.5-27 kg/m2 * Glycated haemoglobin (HbA1c) \< 42 mmol/mol * Normal haemoglobin (8.3-10.5 mmol/l) * Informed and oral and written consent
Exclusion criteria
* Prediabetes, type 1 diabetes or type 2 diabetes or first-degree relatives with type 1 or type 2 diabetes * Nephropathy (eGFR \< 60 and/or albuminuria) * Known liver disease and/or alanine transaminase (ALAT) or aspartate transaminase (ASAT) \> 2 × upper normal limit * Bilirubin \> 25 μmol/l * Known intestinal disease or previous surgery of the intestines * Active or recent malignant disease * Treatment with medicine that cannot be paused for 12 hours * Any condition considered incompatible with participation by the investigators
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Glucagon secretion | 110 minutes | Assessed by difference in absolute plasma glucagon concentrations (measured in pmol/liter) and incremental (baseline-subtracted) area under curve (AUC) for plasma glucagon |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| GLP-1 | 110 minutes | Glucagon-like peptide 1, Measured in pmol/liter |
| GLP-2 | 110 minutes | Glucagon-like peptide 2, Measured in pmol/liter |
| Insulin | 110 minutes | Measured in pmol/liter |
| GIP | 110 minutes | Glucose dependent insulinotropic hormone, Measured in pmol/liter |
| OXM | 110 minutes | Oxytomodulin, Measured in pmol/liter |
| Amino acids | 110 minutes | Measured in pmol/liter |
| CCK | 110 minutes | Cholecystokinin, Measured in pmol/liter |
| Gastrin | 110 minutes | Measured in pmol/liter |
| FGF-19 | 110 minutes | Fibroblast Growth factor 19, Measured in ng/mL |
| FGF-21 | 110 minutes | Fibroblast Growth factor 21, Measured in ng/mL |
| Plasma glucose | 110 minutes | Measured in mmol/liter |
| Norepinephrine | 110 minutes | Measured in pmol/liter |
| GH | 110 minutes | Growth hormone, Measured in nmol/ml |
| P1NP | 110 minutes | Procollagen type I N-terminal propeptide (Bonemarker), Measured in nmol/ml |
| CTX | 110 minutes | C-terminal telopeptide (Bonemarker), Measured in nmol/ml |
| Gallbladder ultrasound | 110 minutes | Measuring of gallbladder size in respons to GLP-2 |
| Glucose infusion | 90 minutes | Amount of glucose infusion (20% v/w) in milliliters needed to clamp at isoglycemic levels (hyperglycemia and hypoglycemia) in respons to GLP-2 |
| Blood pressure | 110 minutes | Systolic (mmHg) and diastolic (mmHg) blood pressure in respons to GLP-2 |
| Heart rate | 110 minutes | Heart rate (beats/minutes) in respons to GLP-2 |
| C-peptide | 110 minutes | Measured in pmol/liter |
| Bile acids | 110 minutes | Measured in nmol/ml |
Countries
Denmark
Outcome results
None listed