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

• Published in: Virologica Sinica Vol. 39; no. 4; pp. 667 - 674
• Main Authors: Chen, Jizheng, Qiu, Pan, Zhao, Tingfeng, Jiang, Haowei, Tursun, Kebinur, Ksimu, Sulaiman, Chen, Xinwen, Wang, Qian
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.08.2024; KeAi Publishing Communications Ltd; Wuhan Institute of Virology, Chinese Academy of Sciences
• Subjects: Adult; Aged; Antiviral agents; Antiviral Agents - therapeutic use; Antiviral drugs; Beta cell (β-cell); Beta cells; Blood Glucose - analysis; Body mass index; Chronic infection; Diabetes; Diabetes mellitus (non-insulin dependent); Diabetes Mellitus, Type 2 - complications; Diabetes Mellitus, Type 2 - drug therapy; Eradication; Fasting; Female; Genotype & phenotype; Glucose; Glucose tolerance; Glucose Tolerance Test; Hepatitis C; Hepatitis C virus (HCV); Hepatitis C, Chronic - complications; Hepatitis C, Chronic - drug therapy; Hepatitis C, Chronic - virology; Humans; Infections; Insulin - therapeutic use; Insulin Resistance; Insulin secretion; Insulin-Secreting Cells - drug effects; Insulin-Secreting Cells - virology; Interferon; Liver cirrhosis; Liver diseases; Male; Metabolism; Middle Aged; Patients; Peptides; Plasma; Prediabetic State - drug therapy; Prediabetic State - virology; Ribavirin; Ribavirin - therapeutic use; Sensitivity analysis; Sustained Virologic Response; Thyroid gland; Type 2 diabetes (T2DM); Ultrasonic imaging; Hepatitis C virus (HCV); Type 2 diabetes (T2DM); Beta cell (β-cell); Insulin secretion
• ISSN: 1995-820X; 1674-0769; 1995-820X
• DOI: 10.1016/j.virs.2024.06.007

The association between chronic HCV infection and type 2 diabetes mellitus (T2DM) has been established; however, there is limited research on β-cell function particularly in the pre-diabetic population. Here, we evaluated indices of β-cell function and insulin sensitivity across the spectrum from normal glucose tolerance to T2DM in individuals with and without chronic hepatitis C (CHC), and the effects of antiviral treatments on these variables. A total of 153 non-cirrhotic, 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 evaluate β-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 HCV-uninfected individuals. Viral eradication through DAA or IFN/RBV therapy demonstrated positive impacts on insulin sensitivity and β-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 of β-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. •β-Cell dysfunction is observed in people with chronic HCV, even in CHC patients with pre-diabetes.•β-Cell dysfunction is observed in the absence of advanced liver disease from HCV.•HCV therapy resulting in SVR substantially improves insulin secretion and improves glycemic control.•Improvements in metabolic health with HCV treatment support efforts at screening and treatment of chronic HCV.