C‐reactive protein and tumor necrosis factor‐alpha in relation to insulin‐mediated glucose uptake, smoking and atherosclerosis

Abstract

Objectives. To examine the hypothesis that serum concentration of C‐reactive protein (CRP) is inversely associated with insulin sensitivity and obesity, and that this may by mediated by tumor necrosis factor‐α (TNFα) and interleukin‐6 (IL‐6). Material and methods. Cross‐sectional, one‐center study of a population‐based sample of 58‐year‐old Swedish men (n = 98). Exclusion criteria were cardiovascular disease, clinical diabetes mellitus and/or continuous cardiovascular medication. Glucose infusion‐rate (euglycemic hyperinsulinemic clamp), adjusted for fat‐free mass, which together with total body fat was measured by dual‐energy X‐ray absorptiometry. Serum concentrations of CRP, TNFα, soluble TNFα receptor 2 (sTNFAR2), IL‐6 determined by ELISA. Ultrasound was used to measure intima‐media thickness (IMT) in both common carotid arteries, carotid bulbs and in the right femoral artery. Results. CRP was inversely associated with insulin sensitivity (r = −0.28, p<0.01) and with total body fat (r = 0.31, p<0.01), but not independently of the TNFα and sTNFAR2 product. Serum CRP, TNFα, sTNFAR2, but not IL‐6, were associated with low insulin sensitivity, total body fat, abdominal obesity, hyperinsulinemia, hypertriglyceridemia, low HDL cholesterol and small LDL particles, i.e. the metabolic syndrome. These associations were independent of smoking and carotid and femoral artery IMT. Conclusions. Serum concentrations of CRP were related to insulin sensitivity and accompanying factors constituting the metabolic syndrome. The results indicate that this association may be mediated by adipose tissue and TNFα effects, the latter measured as the product of TNFα and sTNFAR2. This was a cross‐sectional study and causality cannot be proven.

• Atherosclerosis
• C‐reactive protein
• dyslipidemia
• insulin resistance
• interleukin‐6
• tumor necrosis factor‐alpha
• ultrasound

Acknowledgements

We thank Dr. Lena Bokemark, for assistance with screening of study subjects, and laboratory technologists Caroline Schmidt, Aira Lidell and Carita Fagerlund, for excellent research assistance. The work was supported by grants from the Swedish Heart‐Lung Foundation, the Swedish Medical Research Council (12270,10880), Astra Zeneca Mölndal, Sweden. Conflicts of interest: None.