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Background: Highly sensitive C-reactive protein (hs-CRP) levels are significant predictors of subsequent diabetes and metabolic syndrome (MS). Owing the strong correlations between components of the MS and obesity with hs-CRP levels, previous studies about the associations of hs-CRP with insulin resistance might have been confounded by the inclusion of overweight or dysmetabolic subjects., Design: Our aim was to evaluate the associations between hs-CRP levels and fasting insulin and insulin resistance (evaluated by the Homeostasis Model Assessment: HOMA IR) in a subgroup of subjects with normal body mass index (BMI) and without any metabolic abnormalities. Out of a cohort of 1658 middle-aged subjects, representative of the local sanitary districts of the province of Asti (north-western Italy) enrolled for metabolic screening: 241 (14.5%) showed normal BMI, glucose tolerance, blood pressure and waist values and no dyslipidaemia., Results: In this subgroup of subjects, those with hs-CRP levels > or = 3 mg L(-1) showed significantly higher median insulin and HOMA-IR values (respectively: 20.4 vs. 6.0 pmol L(-1), and 0.8 vs. 0.2 microU mL(-1)x mmol L(-1)). In a multiple regression model, insulin and insulin resistance remained significantly and independently related to hs-CRP levels, after adjustments for age, sex, BMI, waist, alcohol consumption, level of physical activity and smoking habits. Very few individuals within lower fasting insulin quartiles showed hs-CRP values > or = 3 mg L(-1) when compared with approximately 60% of those within the highest quartile., Conclusions: The novel finding is that a state of low-grade systemic inflammation is present in normal BMI subjects who show subclinical insulin resistance but no other metabolic abnormalities.