The Effect of HMG-CoA Reductase Inhibition on Postprandial GLP-1 Secretion

Study Overview
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Brief Summary
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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.

Official Title
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The Effect of HMG-CoA Reductase Inhibition on Postprandial GLP-1 Secretion

Conditions
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Diabetes Mellitus, Type 2, Hydroxymethylglutaryl-CoA Reductase Inhibitors

Intervention / Treatment
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* Drug: Atorvastatin
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Atorvastatin<br>2 weeks treatment with Atorvastatin (1st week 40 mg once daily on day, 2nd week 80 mg (2x40mg) once daily) | Drug: Atorvastatin<br>* Atorvastatin tablet<br>|
| Placebo Comparator: Placebo<br>2 weeks treatment with placebo tablets of comparable sizes and color to the Atorvastatin tablets (1st week one tablet once daily, 2nd week two tablets once daily) | Other: Placebo<br>* Placebo tablet<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Postprandial GLP-1 secretion |  | 240 min | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | 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 | 
| Enteric hormones known to influence glucose metabolism |  | 240 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 | 
| Resting Energy Expenditure |  | At time -20 min, +60 min and +220 min |