Impaired insulin sensitivity as an underlying mechanism linking hepatitis C and posttransplant diabetes mellitus in kidney recipients

Aim of this study was to investigate the mechanism/s associating hepatitis C virus (HCV) infection and posttransplant diabetes mellitus in kidney recipients. Twenty HCV-positive and 22 HCV-negative kidney recipients, 14 HCV-positive nontransplant patients and 24 HCV-negative nontransplant (healthy) subjects were analyzed. A 3-h intravenous glucose tolerance test was performed; peripheral insulin sensitivity was assessed by minimal modeling. Pancreatic insulin secretion, hepatic insulin uptake, pancreatic antibodies and proinflammatory cytokines in serum (tumor necrosis factor-alpha, intereukin-6, high-sensitive C-reactive protein) were also assessed. HCV-positive recipients showed a significantly lower insulin sensitivity as compared to HCV-negative recipients (3.0 +/- 2.1 vs. 4.9 +/- 3.0 min(-1).microU.mL(- 1).10(4), p = 0.02), however, insulin secretion and hepatic insulin uptake were not significantly different. Pancreatic antibodies were negative in all. HCV status was an independent predictor of impaired insulin sensitivity (multivariate analysis, p = 0.008). The decrease of insulin sensitivity due to HCV was comparable for transplant and non-transplant subjects. No significant correlation was found between any of the cytokines and insulin sensitivity. Our results suggest that impaired peripheral insulin sensitivity is associated with HCV infection irrespective of the transplant status, and is the most likely pathogenic mechanism involved in the development of type 2 diabetes mellitus associated with HCV infection.