Type 2 Diabetes, Obesity
Conditions
Keywords
Type 2 diabetes, GLP-1, Bile acid, TGR-5
Brief summary
The purpose of this study is to describe the physiological, pathophysiological and potentially therapeutic implications of bile-induced glucagon-like peptide-1 (GLP-1) secretion in human glucose homeostasis.
Detailed description
The investigators hypothesize that even modest increments in endogenous GLP-1 secretion will elicit important antidiabetic effects of GLP-1. To evaluate whether bile acids have such effects, the investigators plan to perform intraduodenal infusion of two different bile acids and placebo.
Interventions
DRUGColesevelam
Colesevelam 3750 mg dissolved in 100 ml saline, administered in a feeding tube at time = 0.
1.250 mg dissolved in 100 ml saline, administered in a feeding tube at time = 0.
OTHERsaline
100 ml saline
DRUGColesevelam 3750 mg + chenodeoxycholic acid 1250 mg
Colesevelam and chenodeoxycholic acid dissolved in 100 ml saline, administered in a duodenal tube at time = 0.
Sponsors
University Hospital, Gentofte, Copenhagen
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
BASIC_SCIENCE
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
Patients with type 2 diabetes Inclusion Criteria: * danish caucasian ethnicity * normal haemoglobin * BMI \> 25 kg/m2 * HbA1c \< 9% * informed consent
Exclusion criteria
* liver disease(ALT and AST \> upper reference limit) * gastrointestinal disease * liver and biliary tract disease * nephropathy (serum creatinine \> 150 μM, and/or albuminuria) * treatment with insulin, glp-1 analogues and/ or DPP-4 inhibitors * treatment with medicine that can not be paused for 12 hours * previous abdominal surgery eg. cholecystectomy * BMI \< 18,5 kg/m2 or \> 35 kg/m2 Healthy Volunteers Inclusion Criteria: * danish caucasian ethnicity * normal haemoglobin * HbA1c \< 6,0 (American Diabetes Association guidelines) * informed consent
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Change in GLP-1 | At baseline, and at 5, 10, 20, 30, 40, 50, 60, 75, 90, 105, 120, 150 and 180 minutes |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in C-peptide | At baseline, and at 5, 10, 20, 30, 40, 50, 60, 75, 90, 105, 120, 150 and 180 minutes | — |
| Change in glucagon | At baseline, and at 5, 10, 20, 30, 40, 50, 60, 75, 90, 105, 120, 150 and 180 minutes | — |
| Change in glucagon-like-peptide 2 (GLP-2) | At baseline, and at 5, 10, 20, 30, 40, 50, 60, 75, 90, 105, 120, 150 and 180 minutes | — |
| Change in glucose-dependent insulinotropic polypeptide (GIP) | At baseline, and at 5, 10, 20, 30, 40, 50, 60, 75, 90, 105, 120, 150 and 180 minutes | — |
| Change in peptide YY (PYY) | At baseline, and at 5, 10, 20, 30, 40, 50, 60, 75, 90, 105, 120, 150 and 180 minutes | — |
| Change in oxyntomodulin | At baseline, and at 5, 10, 20, 30, 40, 50, 60, 75, 90, 105, 120, 150 and 180 minutes | — |
| Change in insulin | At baseline, and at 5, 10, 20, 30, 40, 50, 60, 75, 90, 105, 120, 150 and 180 minutes | — |
| Change in gastrin | At baseline, and at 5, 10, 20, 30, 40, 50, 60, 75, 90, 105, 120, 150 and 180 minutes | — |
| Change in CCK | At baseline, and at 5, 10, 20, 30, 40, 50, 60, 75, 90, 105, 120, 150 and 180 minutes | — |
| Change in appetite, satiety and prospective food consumption | At baseline, and 30, 60, 90, 120 and 180 minutes | Evaluated by Visual Analog Scale (VAS) |
| Change in gallbladder volume | -30, 0 (baseline), 30, 60, 120 og 180 minutes | Evaluated by ultrasound |
| Change in basal metabolic rate | At -30, 60 og 150 minutes | Evaluated by indirect calorimetry |
| Change in bile acid composition | At -30, 0, 30, 60, 120 og 180 minutes | Evaluated by duodenal aspiration |
| Change in bile acids | At baseline, and at 5, 10, 20, 30, 40, 50, 60, 75, 90, 105, 120, 150 and 180 minutes | — |
Countries
Denmark
Outcome results
None listed