The American Diabetes Association criteria of fasting glucose ≥7.0 mmol/L was used to defined diabetes.24 Subjects with hepatitis B virus Selleck INCB018424 or human immunodeficiency virus coinfection or other causes of liver disease, presence of clinical, histologic, or known diagnosis of cirrhosis or evidence of decompensated liver disease, prior treatment for HCV, steroid or anabolic drug therapy, or those with medical conditions that impaired their ability to participate in the study were excluded. Each subject provided written informed consent prior to enrollment. This study was

approved by the UCSF Internal Review Board, the UCSF Committee on Human Research and SFGH Data LDE225 research buy Governance Committee. Subjects underwent a medical

interview, physical examination including anthropometric measurements, and fasting laboratory evaluation at the screening visit. Seventy-six (88%) subjects underwent a liver biopsy and 89% of those had stage ≤2 fibrosis. Subjects were admitted to the UCSF Clinical and Translational Science Institute-Clinical Research Center (CRC) at SFGH for study tests. A 75-g oral glucose tolerance test (OGTT) was performed at the CRC after an overnight 12-hour fast. Venous blood samples of plasma glucose and insulin were collected at 0, 30, MCE 60, 120, and 180 minutes after an oral ingestion of 75-g glucose load. After another

overnight 12-hour fast, each subject underwent the modified insulin-suppression test.23, 25 The infusion study consisted of two 120-minute periods. During both periods, octreotide was infused at a rate of 0.27 μg m−2 minute−1 to suppress endogenous insulin secretion. Insulin and glucose were infused at rates of 6 mU m−2 minute−1 and 50 mg m−2 minute−1, respectively during the low-dose period to simulate basal conditions and at rates of 32 mU m−2 minute−1 and 267 mg m−2 minute−1, respectively, during the high-dose period in order to achieve physiologic hyperinsulinemia. Blood was drawn for plasma glucose and insulin measurement at 0, 90, 100, 110, 120, 210, 220, 230, and 240 minutes. The four values obtained from 210-240 minutes were averaged to represent the steady-state plasma glucose (SSPG) and the steady-state plasma insulin concentrations (SSPI). Because SSPI concentrations are similar in all patients given identical infusion rates of insulin, the SSPG concentration is a direct measure of the ability of insulin to mediate the disposal of infused glucose load. Higher SSPG concentrations therefore represent higher degrees of insulin resistance. Plasma glucose concentrations were measured by glucose oxidase method (with the YSI 2300 STAT-Plus Analyzer, Yellow Springs, OH).