Correlation of Serum Leptin Levels With Insulin Sensitivity in Patients With Chronic Hepatitis-C Infection

Diabetes is a less-recognized association of hepatitis-C virus (HCV) infection, although several recent studies provide data linking HCV infection and diabetes (1–5). To investigate whether patients with chronic HCV infection without evidence of cirrhosis have an increased risk of diabetes, we conducted a case-control study in 44 consecutive eligible patients with HCV infection and no clinical or histological evidence of cirrhosis and in 20 control subjects without liver disease who were matched by age, sex, and BMI. All 44 patients with chronic HCV infection had biochemical evidence of ongoing inflamation with elevated alanine aminotransferase activity and histologic confirmation. There was no evidence of decompensated liver disease. No patient received any antiviral, immunomodulatory, or immunosuppressive therapy. Immunoreactive insulin was determined by double-antibody radiomimmunosassay (Coat-a-count; Diagnostic Products, Los Angeles, CA). Serum leptin level was determined by the quantitative sandwich enzyme immunoassay technique (Quantikine R & D Human Leptin Immunoassay Systems). Insulin sensitivity was assessed by homeostasis model assessment (HOMA)-estimated insulin sensitivity with the formula that was defined by Matthews et al. (6).

The fasting serum insulin levels were significiantly elevated in patients with chronic HCV infection compared with control subjects (22.5 ± 7.9 vs. 9.0 ± 2.8, P < 0.001). Serum leptin levels were also significiantly elevated in patients with chronic HCV infection compared with control subjects (11.8 ± 4.3 vs. 6.0 ± 3.6, P < 0.001). Fasting serum leptin and insulin levels and HOMA-estimated insulin sensitivity were correlated in the whole group. There was a significant positive correlation between serum leptin and insulin (r = 0.43, P < 0,001) and between leptin and HOMA-estimated insulin sensitivity (r = 0.42, P < 0,01). Mehta et al. (5) reported the analysis of HCV infection and type 2 diabetes in the Third National Health and Nutrition Examination Survey. They reported that patients with HCV infection were more than three times as likely to have type 2 diabetes than those without HCV infection.

In conclusion, our study results suggest that HCV infection may serve as an additional risk factor for the development of type 2 diabetes due to insulin resistance and hyperleptinemia. Investigators from many disciplines will need to prospectively characterize the temporal sequence of HCV infection and type 2 diabetes, define the relationship with serious liver disease, and explicate the biological mechanisms.