Measures of insulin resistance and beta cell function before and after treatment of HCV infection

The association between chronic HCV infection and type 2 diabetes mellitus(T2DM)has been established;however,there is limited research onβ-cell function particularly in the pre-diabetic population.Here,we evaluated indices ofβ-cell function and insulin sensitivity across the spectrum from normal glucose tolerance to T2DMin individuals with and without chronic hepatitis C(CHC),and the effects of antiviral treatments on these variables.A total of 153 noncirrhotic,non-fibrotic CHC patients with a BMI<25 were enrolled in the study.Among them,119 were successfully treated with either direct acting antiviral(DAA)drugs or pegylated interferon/ribavirin(IFN/RBV)anti-HCV therapy.Fasting state-and oral glucose tolerance test(OGTT)-derived indexes were used to evaluateβ-cell function and insulin sensitivity.Among all subjects,19(13%)had T2DM and 21%exhibited pre-diabetes including 8%isolated impaired fasting glucose(IFG)and 13%combined IFG and impaired glucose tolerance(IGT).Early and total insulin secretion adjusted for the degree of insulin resistance were decreased in pre-diabetic CHC patients compared to HCVuninfected individuals.Viral eradication through DAA or IFN/RBV therapy demonstrated positive impacts on insulin sensitivity andβ-cell function in CHC patients who achieved sustained virologic response(SVR),regardless of fasting or OGTT state.These findings emphasize the role of HCV in the development ofβ-cell dysfunction,while also suggesting that viral eradication can improve insulin secretion,reverse insulin resistance,and ameliorate glycemic control.These results have important implications for managing pre-diabetic CHC patients and could prevent diabetes-related clinical manifestations and complications.