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Abstract

Potential conflict of interest: Nothing to report. This work was supported by a contract from the National Institute of Diabetes and Digestive and Kidney Diseases (HHSN276201200161U). We thank Zhao et al. for their interest in our article.1 They make two points. The first is that patients with hepatic decompensation or cirrhosis are at increased risk of diabetes. This relationship is well known and bears no relevance to our findings and conclusions in the general healthy U.S. population. The second point is that factors that we did not consider might have affected the outcomes of our analyses. They offer no hypotheses in this regard, but do point to a published report that found an association of hepatitis C virus (HCV) infection and diabetes that was revealed in multivariate analysis only when controlling for blood cholesterol and triglyceride concentrations.2 No biological reason was suggested for this finding. Nevertheless, we have now considered serum triglyceride and cholesterol concentrations in the main analysis of our article that demonstrated strong relationships of elevated alanine aminotransferase (ALT) and gamma‐glutamyl transferase (GGT) activities with diabetes that were independent of HCV infection (Fig. 2 of the article). Table 1 shows the multivariate odds ratios (ORs) for ALT and anti‐HCV with diabetes when controlling for fasting serum triglyceride and cholesterol concentrations as well as the other cofactors originally considered (age, sex, race/ethnicity, education, body mass index, elevated C‐reactive protein, smoking, alcohol use, and blood transfusion before 1992). As in the published article, an association of elevated ALT was found with diabetes regardless of anti‐HCV status. For study participants with normal ALT activity, there was no association of anti‐HCV and diabetes. Results were similar for ALT with prediabetes, GGT with diabetes and prediabetes, and when HCV RNA status was considered. Table 1 - Multivariate‐Adjusted ORs for Diabetes by HCV and ALT Status Normal ALT Elevated ALT OR 95% CI P Value OR 95% CI P Value HCV negative 1.0 — — 1.84 1.41‐2.40 <0.001 Anti‐HCV positive 0.70 0.30‐1.63 0.41 2.62 1.15‐5.97 <0.001 Abbreviation: CI, confidence interval.