Diabetes Mellitus, Type 2, Hydroxymethylglutaryl-CoA Reductase Inhibitors
Conditions
Brief summary
The primary objective of the present study is to evaluate the effect of HMG-CoA reductase inhibition during 14 days on the postprandial plasma GLP-1 response in healthy individuals. Secondary objectives include the evaluation of HMG-CoA reductase inhibition on postprandial glucose tolerance, gallbladder emptying, gastric emptying, plasma responses of lipids, bile acids and pancreatic and enteric hormones known to influence glucose metabolism and appetite, and faecal content of bile acids and gut microbiota composition.
Interventions
DRUGAtorvastatin
Atorvastatin tablet
OTHERPlacebo
Placebo tablet
Sponsors
University Hospital, Gentofte, Copenhagen
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
BASIC_SCIENCE
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
MALE
Age
18 Years to 70 Years
Healthy volunteers
Yes
Inclusion criteria
* Body mass index (BMI) \>18.5 kg/m2 and \<35 kg/m2 * Caucasian ethnicity * Normal haemoglobin * Glycated haemoglobin (HbA1c) \<43 mmol/mol * Fasting plasma glucose \<6 mmol/l * Informed and written consent
Exclusion criteria
* Diabetes * First-degree relatives with diabetes (both type 1 diabetes and type 2 diabetes) * Liver disease (serum alanine aminotransferase (ALAT) and/or serum aspartate aminotransferase (ASAT) \>2 times normal values) or history of hepatobiliary disorder * Gastrointestinal disease, previous intestinal resection, cholecystectomy or any major intra-abdominal surgery * Reduced kidney function or nephropathy (estimated glomerular filtration rate (eGFR) \<60 ml/min/1.73 m2 (based on serum creatinine) and/or albuminuria * Taking any kind of medicine on a regular basis * Intake of antibiotics two months prior to study * Active or recent malignant disease * Any treatment or condition requiring acute or sub-acute medical or surgical intervention * Any condition considered incompatible with participation by the investigators * If the subjects receive any antibiotic treatment while included in the study they will be excluded
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Postprandial GLP-1 secretion | 240 min |
Secondary
| Measure | Time frame |
|---|---|
| Postprandial Bile Acid Composition | 240 min |
| Postprandial total plasma Bile Acid | 240 min |
| Postprandial Glucose Tolerance | 240 min |
| Postprandial plasma lipid response | 240 min |
| Postprandial GIP secretion | 240 min |
| Resting Energy Expenditure | At time -20 min, +60 min and +220 min |
| Gallbladder emptying | 240 min |
| Faecal content of bile acid | One sample collected on day 12 or 13 of the intervention |
| Gut microbiota composition | One sample collected on day 12 or 13 of the intervention |
| Gastric emptying | 240 min |
| Enteric hormones known to influence glucose metabolism | 240 min |
Countries
Denmark
Outcome results
None listed