Type 1 Diabetes, Type 2 Diabetes
Conditions
Keywords
Glucagon-like peptide-1, Glucagon, Normal physiology, T2DM, T1DM
Brief summary
Diabetes(both types) are recognized by high levels of glucagon in the circulation. Glucagon is known to increase blood glucose, and might therefore contribute to the respective diseases. Under some circumstances the gut hormone GLP-1 inhibits the glucagon secretion. The investigators aim to identify the impact of GLP-1 on the glucagon secretion, at increasing blood glucose levels in healthy subjects, in patients with type 2 diabetes, and in patients with type 1 diabetes. The investigators think that the effect of GLP-1 on the glucagon secretion might be dependent of blood glucose levels.
Interventions
DRUGNative human Glucagon-like Peptide-1 ( GLP-1(7-36))
Continuous iv. infusion of the native gut hormone GLP-1 (0.2 pmol/kg/min) for 210 minutes. Combined with a step wise glucose clamp using 20% w/w glucose iv. infusion reaching plasma glucose value of 15 mM starting at fasting plasma glucose (30 min per step)
DRUGNaCl
Continuous iv. saline infusion (NaCl Isotonic) for 210 minutes. Combined with a step wise glucose clamp using 20% w/w glucose iv. infusion reaching plasma glucose value of 15 mM starting at fasting plasma glucose (30 min per step)
Sponsors
University Hospital, Gentofte, Copenhagen
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
BASIC_SCIENCE
Masking
SINGLE (Subject)
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
Yes
Inclusion criteria
Patients with T2DM * Above the age of 35 years, treatment with diet or oral anti-diabetic medication. Diagnosed with T2DM in at leat three months in advance(WHO criterion) * Normal hemoglobin * Informed content Patients with T1DM * T1DM (WHO criterion) * Plasma-C-peptid negative due to arginin-test * Normal hemoglobin * age\> 18 years * Informed content Healthy subjects * Normal fasting plasma glucose and normal glucose tolerance (WHO criterion) * Normal hemoglobin * Age \>18 years * Informed content
Exclusion criteria
Patients with T2DM * Treatment with glitazones and/or gliptins * Inflammatory bowels disease * previous bowel resection with or without stomy * Nephropathy (serum creatinin \>150 µM and/or albuminuria) * Liver disease (serum alanine-aminotransferase (ALAT) and/or serum aspartate-aminotransferase (ASAT) \>2×normal values) * Medical treatment impossible to break for 12h. * Age \>80 years Patients with T1DM * Overweight (BMI \>30 kg/m2) * Inflammatory bowels disease * previous bowel resection with or without stomy * Nephropathy (serum creatinin \>150 µM and/or albuminuria) * Liver disease (serum alanine-aminotransferase (ALAT) and/or serum aspartate-aminotransferase (ASAT) \>2×normal values) * Medical treatment impossible to break for 12h (except treatment with insulin). * Age \>80 years Healthy subjects * Diabetes * Prediabetes (impaired glucose tolerance and/or impaired fasting plasma glucose) * First order relatives with diabetes * Overweight (BMI \>30 kg/m2) * Inflammatory bowels disease * previous bowel resection with or without stomy * Nephropathy (serum creatinin \>150 µM and/or albuminuria) * Liver disease (serum alanine-aminotransferase (ALAT) and/or serum aspartate-aminotransferase (ASAT) \>2×normal values) * Medical treatment impossible to break for 12h. * Age \>80 years
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Plasma Glucagon response to the GLP-1 infusion / glucose clamp | At 0, 15, 30, 45, 60, 75, 90, 105, 120, 135, 150, 165, 180, 195, 210 min | The collection of blood samples will be done during the 210 min GLP-1 infusion / glucose clamp-session |
| Plasma GLP-1 response to the GLP-1 infusion / glucose clamp | At 0, 15, 30, 45, 60, 75, 90, 105, 120, 135, 150, 165, 180, 195, 210 min | The collection of blood samples will be done during the 210 min GLP-1 infusion / glucose clamp-session |
| Plasma Glucose response to the GLP-1 infusion / glucose clamp | At 0, 15, 30, 45, 60, 75, 90, 105, 120, 135, 150, 165, 180, 195, 210 min | The collection of blood samples will be done during the 210 min GLP-1 infusion / glucose clamp-session |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| plasma GIP response to the GLP-1 infusion / glucose clamp | At 0, 15, 30, 45, 60, 75, 90, 105, 120, 135, 150, 165, 180, 195, 210 min | The collection of blood samples will be done during the 210 min GLP-1 infusion / glucose clamp-session |
| Resting Metabolic Rate response to the GLP-1 infusion / glucose clamp | at 0, 120, and 180 min | Assessed by indirect calorimetry during the GLP-1 infusion / glucose clamp-session |
| Food Intake | at 210 min | Assessed by ad'libitum meal after the 210 min GLP-1 infusion / glucose clamp. |
| Hunger scores response to the GLP-1 infusion / glucose clamp | At 0, 15, 30, 45, 60, 75, 90, 105, 120, 135, 150, 165, 180, 195, 210 min | Assessed by VAS during the 210 min GLP-1 infusion / glucose clamp-session |
| plasma Insulin response to the GLP-1 infusion / glucose clamp | At 0, 15, 30, 45, 60, 75, 90, 105, 120, 135, 150, 165, 180, 195, 210 min | The collection of blood samples will be done during the 210 min GLP-1 infusion / glucose clamp-session |
Countries
Denmark
Outcome results
None listed