Association of Hepatitis C and Diabetes Mellitus

TO THE EDITOR:

The report by Mehta and colleagues (1) on the association between HCV infection and type 2 diabetes mellitus is intriguing. In the accompanying editorial, Alexander states that “a clear biological link … is not obvious” and summarizes the possible biological mechanisms that may be responsible for the observed link (2). One possibility that was not highlighted is the association between hepatitis C and iron overload, which may partly explain the observed findings (3). Of importance, in a different analysis of NHANES III data, Ford and Cogswell found a significant association between elevated serum ferritin level and newly diagnosed diabetes (4). To determine whether ferritin was associated with type 2 diabetes mellitus and HCV, I performed a descriptive analysis of the same NHANES III data set. Persons in NHANES III with antibodies to hepatitis C had a higher mean (±SE) serum ferritin level (202.7± 12.7 µ/L vs. 132.9±1.1 µ/L; P< 0.001) (values are adjusted for unequal variance). In a subset of persons with antibodies to HCV, those with type 2 diabetes mellitus had a mean ferritin level of 329.3±74.0 µ/L, compared with 187.5±10.9 µ/L in those without (P = 0.06). When survey statistical methods were used to account for the complex design of NHANES (5), the estimated population mean was 356.8 µ/L (95% CI, 245.6 to 468.0 µ/L) for HCV-infected patients with diabetes and 202.7 µ/L (CI, 169.9 to 235.4 |gmg/L) for HCV-infected patients without diabetes. Given these differences, it would be interesting to know the possible effect of serum ferritin level on the results of Mehta and colleagues' multivariable model of HCV infection and type 2 diabetes mellitus. Whether serum ferritin is a confounder, a marker of disease severity, or a part of the causal pathway of diabetes among HCV-infected persons is a subject for further research.