Effect of Bile Acids on GLP-1 Secretion

University Hospital, Gentofte, Copenhagen

Status: Completed

Conditions: Obesity; Type 2 Diabetes

Treatments: Drug: Chenodeoxycholic Acid; Drug: Colesevelam 3750 mg + chenodeoxycholic acid 1250 mg; Drug: Colesevelam; Other: saline

Study type: Interventional

Funder types: Other

Identifiers

NCT01666223

H-1-2012-049

Details and patient eligibility

About

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.

Full 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.

Enrollment: 20 patients

Sex: All

Ages: 18+ years old

Volunteers: Accepts Healthy Volunteers

Inclusion and exclusion 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

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 medicine that can not be paused for 12 hours
• previous abdominal surgery eg. cholecystectomy
• BMI < 18,5 kg/m2 or > 35 kg/m2
• first degree relatives diagnosed with diabetes
• previously diagnosed with diabetes, or treated with antidiabetic agents

Trial design

Primary purpose: Basic Science

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: Triple Blind

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20 participants in 4 patient groups

Colesevelam

Experimental group

Treatment:

Drug: Colesevelam

Chenodeoxycholic acid

Experimental group

Treatment:

Drug: Chenodeoxycholic Acid

Colesevelam + chenodeoxycholic acid

Experimental group

Treatment:

Drug: Colesevelam 3750 mg + chenodeoxycholic acid 1250 mg

Placebo

Experimental group

Treatment:

Other: saline