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The aim of the study was to determine the association of high sensitivity C-reactive protein (hs-CRP) with body fat, diabetes and coronary artery disease (CAD) in an urban south Indian population. The study was conducted on 150 subjects selected from the Chennai Urban Rural Epidemiology Study (CURES), an ongoing population-based study on a representative population of Chennai (formerly Madras). Group 1 comprised of non-diabetic subjects without CAD ( n = 50). Type 2 diabetic subjects without CAD formed Group 2 ( n = 50); Group 3 comprised of Type 2 diabetic subjects with CAD ( n = 50). CAD was diagnosed based on electrocardiographic (ECG) changes suggestive of ST segment depression and/or Q wave changes using appropriate Minnesota codes. All study subjects were non-smokers, and had no infectious or inflammatory diseases. The plasma levels of hs-CRP were measured using a highly sensitive nephelometric assay. Body fat was calculated using Siri's formula using skin fold measurements. Diabetic subjects with (2.89 mg/l) and without (2.25 mg/l) CAD had significantly higher hs-CRP levels compared with non-diabetic subjects without CAD (0.99 mg/l, P < 0.001). hs-CRP values increased with increases in tertiles of body fat ( anova P < 0.001) and HbA1c ( anova P < 0.001). Multiple logistic regression analysis revealed hs-CRP to be strongly associated with CAD (OR: 1.649, P = 0.040) and diabetes (OR: 2.264, P = 0.008) even after adjusting for age and gender. Regression analysis also revealed body fat to be strongly associated with diabetes and CAD even after adjusting for age and gender ( P < 0.001). hs-CRP influenced this association for diabetes but not for CAD. hs-CRP showed a strong association with CAD and diabetes, even after adjusting for age and gender. The association of body fat with diabetes seems to be mediated through hs-CRP. However, hs-CRP does not appear to mediate the relationship between body fat and CAD. Diabet. Med. 22, 863 –870 (2005) [ABSTRACT FROM AUTHOR]