type 2 diabetes mellitus
Conditions
Interventions
In phase 1, the healthy subjects will be randomized into 2 groups. The first group (N=10) will receive 10 mg/kg/day gDCA for 30 days, the other group (N=10) will receive 10 mg/kg/day enteric coated gD
Sponsors
Academic Medical Center (AMC), Amsterdam, The Nettherlands
Eligibility
Inclusion criteria
Inclusion criteria: In order to be eligible to participate in this study, a subject must meet all of the following criteria: •Ability to provide informed consent •Age: 18 years or older at the time of signing the informed consent Specific inclusion criteria for the healthy lean subjects group: •BMI 18,5 – 25 kg/m2 or a BMI between 25 and 30 kg/m2 and waist circumference between 79 cm and 94 cm. •HOMA-IR index: ≤ 2.0 (measured as fasting insulin (pmol/L) x fasting glucose (mmol/L)) / 135) Specific inclusion criteria for the T2D patients group: •Stable T2D treated with diet and/or medication only (medication not changed in the past 3 months) •HbA1c 53-64 mmol/mol •BMI > 25 kg/m2
Exclusion criteria
Exclusion criteria: •Use of medication that interferes with BA metabolism (colesevelam, colestimide, ursodeoxycholic acid). •Diabetes treatment with dipeptidyl peptidase-4 inhibitors, GLP-1 receptor agonists or insulin •Hypercholesterolemia treatment with statins or fibrates unless on a stable dose for at least 3 months prior to screening •Use of nicotinic acid or derivates of nicotinic acid within 4 weeks prior to screening •Presence of contra indications for the use of ezetimibe (see SPC) •Use of other medication such as the following: vitamin K antagonists, ciclosporine, antacids containing aluminium hydroxide or aluminium oxide •Cholecystectomy •Gastro-intestinal disorders, including gallstone disease •Nefropathy checked by blood chemistry (creatinine, eGFR) •Liver disease checked by blood chemistry (ASAT, ALAT, GGT, AF, bilirubin) •Weight increase or decrease >10% in previous 3 months •Alcohol use >3 units/day •Tobacco use •XTC, cannabis, cocaine or opioids abuse •Likely to leave the study before its completion •Participation in other intervention studies 3 months before or after the duration of this study.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Secretion of GLP-1 and insulin, postprandial inflammation and postprandial hyperlipidemia. THe primary objective of phase 1 is to determine safety of long-term gDCA administration in healthy volunteers. | — |
Secondary
| Measure | Time frame |
|---|---|
| The effect of gDCA administration on bile acid metabolism, glucoregulatory and gut hormones, resting energy expenditure, microbiome, appetite and satiety, cholesterol elimination. | — |
Contacts
Public ContactM.R. Soeters
Academic Medical Center (AMC) Department of Endocrinology & Metabolism, F5-162 P.O. Box 22660
Outcome results
None listed