Evaluation of factors controlling glucose tolerance in patients with HCV infection before and after 4 months therapy with interferon-alpha

Background Epidemiological data suggest that chronic hepatitis C virus (HCV ) infection may contribute to the development of diabetes mellitus. Therapy of HCV infection with recombinant interferon-alpha (r-IFN-alpha) can also impair of glucose metabolism. Methods To investigate the impact of HCV infection and the therapy with r-I FN-alpha on glucose metabolism we measured insulin sensitivity, glucose eff ectiveness, and first and second phase insulin secretion, using the minimal modelling analysis of frequently sampled intravenous glucose tolerance tes ts in 13 nondiabetic patients with HCV-induced liver disease before and aft er therapy with r-INF-alpha (6 x 10(6) U, subcutaneously, three times a wee k over 4 months). Liver biopsy was performed to evaluate and score liver fi brosis as a marker of HCV-induced cell injury. Results Insulin sensitivity (r = -0.59, P < 0.05) and first phase insulin s ecretion (r = -0.66, P < 0.03) were negatively related to the fibrosis scor e. Insulin sensitivity rose from 1.96 (SEM 0.37, n = 8) to 5.69 (SEM 0.99, n = 8) 10(-4) min(-1) per mu U mL(-1) (P < 0.01) in responders and from 2.5 1 (SEM 0.61, n = 5) to 6.95 (SEM 1.99, n = 5) in nonresponders after 4 mont hs r-INF-alpha therapy. Fasting free fatty acids decreased significantly to about 50% (P < 0.01) in patients with and without therapy response after 4 months, whereas first phase insulin secretion did not change. Conclusions HCV-induced liver injury is related to the deterioration of ins ulin sensitivity and first phase insulin response, thus impairing glucose h omeostasis in these HCV-infected patients. The administration of r-INF-alph a three times a week over 4 months is not associated with an impairment of glucose homeostasis.