Hepatitis C Virus Infection: Evidence for an Association With Type 2 Diabetes

Response to Antonelli et al.

Antonelli et al. (1) classified diabetes associated with hepatitis C virus (HCV) infection as type 2. However, these patients show slightly different phenotype than typical type 2 diabetic subjects. Of interest, in our study, HCV diabetic patients presented similar intermediate clinical phenotype with significantly lower BMI (26.5 ± 4.8 vs. 30.9 ± 6.3 kg/m²), systolic (133.9 ± 14.0 vs. 142.9 ± 25.6 mmHg) and diastolic (84.4 ± 10.2 vs. 88.1 ± 16.0 mmHg) blood pressure, LDL cholesterol (1.9 ± 0.5 vs. 2.7 ± 0.8 mmol/l), and triglycerides (1.4 ± 0.8 vs. 2.6 ± 1.9 mmol/l). Furthermore, these patients showed lower C-reactive protein concentration (1.53 ± 1.23 vs. 3.54 ± 2.53 mg/l).

There is a groundswell of data now to link HCV infection with diabetes. However, serious doubt concerning the true character of diabetes in HCV patients must be emphasized. An autoimmune basis of the HCV-diabetes link is unlikely because no increased prevalence of β-cell autoimmune markers in HCV patients has been found (2). Nonetheless, there is a report of type 1 diabetes 1 year after blood transfusion–related HCV infection (3). Additionally, diabetic HCV patients with mixed cryoglobulinemia are more likely to carry non–organ-specific autoantibodies (4). Interestingly, there is evidence to support the hypothesis that HCV directly damages β-cells or disturbs their function, which ultimately leads to diabetes (5). Finally, there is no question that HCV, by itself, can induce insulin resistance, disturbing the insulin signaling pathway by the function of HCV core protein (6). Moreover, a crucial association between diabetes and the stage of fibrosis in HCV patients, independent of obesity and steatosis, on liver biopsy has also been demonstrated (6).

Diabetes in HCV patients has a unique and complex pathogenesis. Although both insulin resistance and β-cell dysfunction are responsible for the diabetes-HCV association, the specific nature of that link casts doubt on diagnosis of type 2 diabetes in these patients.