Quantifying Hepatic Mitochondrial Fluxes in Humans

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 analyses.