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The aim of this study was to describe the association between hepatitis C virus (HCV) infection and type 2 diabetes among a group of American-Indian women who were screened for both conditions.The study population was a convenience sample of women who were receiving prenatal care. All women were systematically screened for both HCV and diabetes.A total of 426 women were included in the sample. HCV infection was detected in 13 (3.1% [95% CI 1.7-5.0]) and type 2 diabetes in 22 (5.2%, [3.3-7.6]) women. Women diagnosed with type 2 diabetes were more obese and had higher serum alanine aminotransferase activity compared with women without diabetes. Four of 13 (30.8% [10.6-58.7]) HCV-infected women and 18 of 413 (4.4% [2.7-6.7]) women without evidence of HCV infection had type 2 diabetes. (odds ratio 9.8 [95% CI 2.4-34.0], Fisher's exact test P = 0.003). In a logistic regression model, increasing age (10-year increments), obesity (by standard deviations from the mean BMI), and positive HCV status were each independently related to the diagnosis of diabetes.Among American-Indian women, type 2 diabetes is more common in those with than in those without HCV infection. This association and its potential mechanisms may have clinical implications. Investigation into the mechanisms linking HCV infection to the expression of type 2 diabetes may also help to define processes that promote the development of type 2 diabetes in susceptible individuals.