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Background The association between hepatitis C virus ( HCV) infection and the occurrence of type II diabetes remains controversial. Prospective studies are needed to assess its causal temporality. Methods A cohort of 21 559 adults enrolled from seven townships in Taiwan during 1991-1992 and followed till the end of 2010. Incident diabetes over a study time period from 2000 to 2010 was ascertained through computerized linkage with the National Health Insurance database and the National Death Certification profiles. Cox's proportional hazards models were used to estimate hazard ratios ( HRs) with 95% confidence intervals ( CIs). Antibodies against HCV (anti- HCV) were tested for all participants, and serum HCV RNA levels were measured for anti- HCV seropositives. Results During 180 244 person-years of follow-up, there were 1917 incident diabetes cases recorded. The cumulative risk for diabetes was 10.9% for anti- HCV seronegatives and 16.7% for anti- HCV seropositives respectively. The HR for diabetes of anti- HCV seropositivity was 1.53 (95% CI: 1.29-1.81) compared with anti- HCV seronegatives after adjustment for risk predictors. The adjusted HRs were 1.63 (1.31-2.02) for anti- HCV seropositives with positive HCV RNA compared to anti- HCV seronegatives ( P<.001). Conclusion Chronic HCV infection was associated with an increased risk for diabetes after adjustment for other risk predictors. [ABSTRACT FROM AUTHOR]