Does C-reactive protein identify a subclinical metabolic disease in healthy subjects?

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 ≥ 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 µU mL−1× 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 ≥ 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.