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

Response to Skowroński et al.

We agree with Skowroński et al. (1) that the type of diabetes manifested by patients with HCV chronic infection (HCV⁺) may not be classical type 2 diabetes, and the phenotypic characterization of our patients shows just that. The labeling of HCV⁺ patients as type 2 diabetes is purely conventional and possibly inaccurate: the lines separating type 1 diabetes, from latent autoimmune diabetes in adults and from type 2 diabetes, are fading away as new pathogenetic information is obtained (2).

HCV chronic infection may be responsible for a constellation of extrahepatic immune-mediated manifestations (3). HCV lymphotropism may trigger lymphocyte expansion followed by the production of different autoantibodies (3). For example, we have previously reported (4) on 229 HCV-related mixed cryoglobulinemia (MC-HCV⁺) patients without cirrhosis. We found that 1) the prevalence of type 2 diabetes was significantly higher in MC-HCV⁺ patients without cirrhosis than in control subjects (14.4 vs. 6.9%), 2) MC-HCV⁺ patients with type 2 diabetes were leaner than type 2 diabetic control subjects (24.2 vs. 30.4 kg/m²) and showed significantly lower LDL cholesterol and systolic and diastolic blood pressure, and 3) MC-HCV⁺ patients with type 2 diabetes had non–organ-specific autoantibodies more frequently (34 vs. 18%) than nondiabetic MC-HCV⁺ patients. Thus, in HCV chronic infection, the clinical phenotype of diabetes has been found to be similar across three studies (1,4,5) and different from classical type 2 diabetes. An immune-mediated mechanism for MC-HCV⁺–associated diabetes has been postulated (4), and a similar pathogenesis might be involved in the diabetes of HCV⁺ patients. This hypothesis is strengthened by the finding that autoimmune phenomena in type 2 diabetic patients are more common than previously thought (6). Since the prevalence of classic β-cell autoimmune markers in HCV⁺ patients has not been found to be increased (1), other immune phenomena might be involved, and viral damage to the β-cells may occur by a direct mechanism (7).