We read with interest the article by Lecube et al. (1), which indicated that tumor necrosis factor (TNF)-α is a mechanism by which hepatitis C virus (HCV)-infected patients are more prone to develop type 2 diabetes than patients with other chronic liver diseases. The mechanisms of the development of insulin resistance in patients with chronic HCV infection are not well understood. Insulin resistance in HCV-infected patients occurs already at an early stage in the course of HCV infection (2). Furthermore, although steatosis was more severe in patients infected with genotype 3, insulin resistance was associated with steatosis only in patients infected with genotype 1 (3).
Recently, we investigated the role of adipocytokines in HCV-related steatosis (4). Seventy-one chronic HCV patients were studied to assess the effects of adipocytokines on steatosis. We used an enzyme-linked immunosorbent assay to determine serum TNF receptors (TNF-R) I and II concentrations. Based on the findings in the study by Lecube et al. (1), we investigated whether plasma TNF-RI and TNF-RII concentrations were associated with parameters of insulin resistance in the 68 noncirrhotic subjects of this group of patients. Genotype distributions were as follows: genotype non-3, n = 55; genotype 3, n = 13.
TNF-RII and TNF-RI concentrations were correlated with homeostasis model assessment (r = 0.26, P = 0.02 and r = 0.20, P = 0.09, respectively). Homeostasis model assessment was significantly different in patients with genotype 3 than in patients with genotype non-3 (1.13 vs. 2.46; P = 0.01). There were no significant differences between the two groups for age, BMI, TNF-RI, and TNF-RII concentrations (genotype 3 versus non-3: TNF-RI = 1.64 vs 1.48 pg/ml, P = 0.32; TNF-RII = 3.79 vs. 3.41 pg/ml, P = 0.39).
Our results suggest that the HCV genotype must be included in further study evaluating insulin resistance in HCV-infected patients. Moreover, the lack of difference of TNF-R concentrations between subjects with HCV genotype 3 and non-3, despite a significant difference for homeostasis model assessment level, suggests that factors other than TNF-α could be implicated in the development of insulin resistance during HCV chronic infection.
