fatty liver Non-alcoholic fatty liver (NAFL)
Conditions
Interventions
None listed
Sponsors
Universiteit Maastricht
Eligibility
Age
18 Years to 64 Years
Inclusion criteria
Inclusion criteria: - Caucasian (people will be excluded when having a *50% racial African/Asian background) - Male or postmenopausal female - Aged 45-75 years - Body mass index (BMI) 27 * 38 kg/m2 - Stable dietary habits (no weight loss or gain >3kg in the past 3 months) - Sedentary lifestyle (not more than 2 hours of vigorous exercise per week)
Exclusion criteria
Exclusion criteria: - Type 2 diabetes (fasted blood glucose > 7mmol/l) - Any condition or medical history that would in the investigator*s or dependent physician's opinion interfere with the study, with study outcomes or increase the risk of the study procedures - Alcohol consumption of >2 servings per day - Smoking - Use of medication known to interfere with the safety of study procedures - Use of medication known to increase liver fat, like for instance corticosteroids (parenteral & oral chronic administration only), amiodarone (Cordarone), tamoxifen (Nolvadex), and methotrexate (Rheumatrex, Trexall). - Subjects receiving thiazoledinediones (glitazones [pioglitazone, rosiglitazone]). - Participation in research or medical examination that included PET/CT scanning in the last 3 months -Contra-indication for MRI -Low Hb(men:
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| * Insulin-stimulated glucose uptake measured by PET Insulin-stimulated hepatic glucose uptake rate (ki) measured by [18F]-FDG PET. Influx rate measured (Ki) in mL/cm3/min, by *using the irreversible two- tissue compartment Patlak method (Patlak et al. 1983) in each voxel.* * Hepatic fat content Liver fat will be quantified by 1H-MRS with which the water and fat resonances can be detected. The intensity of the fat resonance will be expressed relative to the water resonance (%). | — |
Secondary
| Measure | Time frame |
|---|---|
| * Hepatic insulin sensitivity measured by H-E Clamp Hepatic insulin sensitivity is measured as % suppression of endogenous glucose production and peripheral insulin sensitivity is measured as Rd in *mol/kg/min. During the clamp, four blood samples in time are taken during each of the three steady states (basal, low insulin and high insulin phase). The average of these four blood samples will be taken for further calculations regarding glucose tracer kinetic: rate of appearance (Ra) and Rd. Calculations for non-steady-state Ra and Rd during the clamp will be performed as described by Wolfe et al. and Steele et al. (10, 11). Endogenous glucose production will be calculated as Ra minus GIR. * Whole-body insulin sensitivity is measured as GIR in *mol/kg/min * Hepatic fatty acid composition Liver fat will be quantified by 1H-MRS with which the water and fat resonances can be detected. The intensity of the fat resonance will be expressed relative to the water resonance (%). Hepatic fatty acid composition is measured as relative amount of SFA, MUFA and PUFA to the total amount of fatty acids determined by MRS. * De Novo Lipogenesis DNL is measured as relative contribution of newly synthesized palmitate in the VLDL-TG pool expressed as %DNL. The fasted blood sample drawn at visit 2 will be used for determination of newly synthesized palmitate in the VLDL-TG pool. | — |
Countries
Netherlands
Outcome results
None listed