Effects of metformin on hepatic lipid metabolism

Phase 1

Conditions: Type 2 diabetes and dyslipidemia
MedDRA version: 14.1Level: PTClassification code 10067585Term: Type 2 diabetes mellitusSystem Organ Class: 10027433 - Metabolism and nutrition disorders
Therapeutic area: Body processes [G] - Physiological processes [G07]

Registration Number: EUCTR2012-000808-16-DK

Lead Sponsor: Aarhus University Hospital

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: Not specified

Inclusion Criteria

Group 1: Diabetes subjects:

- newly diagnosed (>3 og <12 months) type 2 diabetes
- Age 50-70 years
- BMI<40

Group 2: Healthy controls

- Age 50-70 years
- BMI<40
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 30
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 6

Exclusion Criteria

- metformin treatment >6 months
- Non-alcoholic steatohepatitis
- Cancer
- Anaemia
- HbA1C>8.5 %
- Other clinically meaningful abnormal biochemical parameter
- Pancreatitis
- Alcohol or substance abuse
- Allergy towards metformin
- Claustrophobia
- Severe obesity >130 kg

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: It is the general purpose of the trial to investigate whether the positive effects of metformin on blood lipids are caused by improved glycemic control and changes in body composition or if they are caused by direct effects on lipid metabolism. We specifically plan to:<br>- investigate hepatic fatty acid uptake, reesterification and oxidation assessed by positron emission tomography (PET)<br>- investigate the effect of metformin on whole body VLDL-TG oxidation and redeposition in adipose tissue.;Secondary Objective: Not applicable;Primary end point(s): -hepatic FFA uptake ([11C]palmitate – PET technique)<br>- hepatic FFA oxidation ([11C]palmitate – PET technique)<br>-hepatic FFA reesterification ([11C]palmitate – PET technique)<br>;Timepoint(s) of evaluation of this end point: 3 months treatment

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): - VLDL-TG secretion ([14C]VLDL – isotope dilution technique)<br>-VLDL-TG oxidation (14CO2 in breath) <br>-VLDL-TG redeposition in adipose tissue. (fat biopsy ~ 1 g)<br>-Insulin sensitivity in the liver and peripheral tissues [3H]glucose – isotope dilution technique<br>-Body composition (DEXA) <br>-Intracellular signalling in muscle and adipose tissue (AMPK, LKB1, ACC, CD36, ATGL, HSL, perilipin, G0S1, CGI58, GLUT4, og cytochrom C)<br>;Timepoint(s) of evaluation of this end point: 3 months treatment