Quantitation of Hepatic Mitochondrial Fluxes in Humans With Nonalcoholic Fatty Liver Disease (NAFLD)
The University of Texas Health Science Center at San Antonio
Summary
In this study the investigators will quantitate hepatic mitochondrial fluxes in T2D patients with NAFL and NASH before and after 16-weeks treatment with the insulin sensitizer pioglitazone
Description
The study team will examine hepatic mitochondrial TCA flux and pyruvate cycling (oral \[U-13C\]-propionate), hepatic gluconeogenesis (oral 2H2O), and hepatic insulin sensitivity (intravenous \[3,4-13C2\]-glucose with euglycemic insulin clamp) before and after 16 weeks treatment with the FDA approved insulin sensitizer pioglitazone. These studies will be performed in (i) type 2 diabetic subjects with NAFL but without evidence of fibrosis, and (ii) type 2 diabetic patients with NASH. Liver biopsies will be obtained before and after treatment for the diagnosis of NAFL/NASH and for molecular analy…
Eligibility
- Age range
- 18–80 years
- Sex
- All
- Healthy volunteers
- No
T2D with NAFL Inclusion Criteria: * Confirmed T2D based on OGTT (2 h glucose ≥200 mg/dl). * Treated with diet, metformin, and/or sulfonylurea and in good general health determined by medical history, physical exam, and routine blood chemistries; * age = 18-80 years; * BMI = 25-40 kg/m2; * HbA1c = 7-10%; stable body weight (±4 pounds) over the preceding 3-months; * not taking any medication known to affect glucose metabolism other than antidiabetic medications. * Evidence of moderate/severe fatty liver (steatosis; grade S2/S3 on FibroScan corresponding to ≥10% fat on MRI-PDFF) and no/minimal…
Interventions
- DrugPioglitazone
An insulin sensitizer and anti-diabetic agent. Participants will be started on 15 mg/day, increased to 30 mg/day at week 2 and then to 45 mg/day at week 4.
- OtherPlacebo
Placebo for pioglitazone
Locations (2)
- Texas Diabetes Institute - University Health SystemSan Antonio, Texas
- University of Texas Health Science Center at San AntonioSan Antonio, Texas