The effect of the secondary bile acid glycodeoxycholic acid as a therapy for diabetes.

INTERVENTION: 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 gDCA for 30 days. The first 5 healthy subjects will be included in the treatment arm giving normal/regular gDCA. When no SAEs occur, the next step will be to include 5 healthy subjects in the arm giving enteric coated gDCA. When no SAEs occur the last 10 subjects will be assigned according to a predefined scheme. At the phase 2 we include 10 T2D male patients. The 10 T2D patients will receive gDCA or enteric coated gDCA. The dosage and which form of gDCA (normal or enteric coated) will be based on the results of the pilot study (phase 1) regarding safety. In the third (final) phase we want to include10 T2D male patients. The 10 T2D patients receive (enteric coated) gDCA (depending on phase 1) and 20 mg ezetimibe per day for 30 days. CONDITION: Diabetes Mellitus Type 2 (DM type II) ; ; PRIMARY OUTCOME: 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 OUTCOME: The effect of gDCA administration on bile acid metabolism, glucoregulatory and gut hormones, resting energy expenditure, microbiome, appetite and satiety, cholesterol elimination. 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 20 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