Quantifying Hepatic Mitochondrial Fluxes in Humans

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 hepatic fibrosis (grade F0/F1 on FibroScan). Exclusion Criteria: * Alcohol consumption \>14 units/week for women and \>21 units/week for men. * Cirrhosis (fibrosis stage 4). * Type 1 diabetes and/or GAD positive subjects. * Subjects not drug naive or have been on metformin more than 3 months. * Presence of proliferative retinopathy. * Urine albumin excretion \> 300 mg/day. * Evidence of other forms of chronic liver disease, including alcoholic liver disease, hepatitis B and C, primary biliary cholangitis, suspected/proven liver cancer and any other liver disease other than NAFLD. * History of NY Class III-IV heart failure T2D with NASH 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% liver fat on MRI-PDFF) and moderate/severe hepatic fibrosis (grade F2/F3 on FibroScan). Exclusion Criteria: * Alcohol consumption \>14 units/week for women and \>21 units/week for men. * Cirrhosis (fibrosis stage 4). * Type 1 diabetes and/or GAD positive subjects. * Subjects not drug naive or have been on metformin more than 3 months. * Presence of proliferative retinopathy. * Urine albumin excretion \> 300 mg/day. * Evidence of other forms of chronic liver disease, including alcoholic liver disease, hepatitis B and C, primary biliary cholangitis, suspected/proven liver cancer and any other liver disease other than NAFLD. * History of NY Class III-IV heart failure