C-reactive protein and tumor necrosis factor-alpha in relation to insulin-mediated glucose uptake, smoking and atherosclerosis.
OBJECTIVE
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-alpha (TNFalpha) and interleukin-6 (IL-6).


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, TNFalpha, soluble TNFalpha 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 TNFalpha and sTNFAR2 product. Serum CRP, TNFalpha, 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 TNFalpha effects, the latter measured as the product of TNFalpha and sTNFAR2. This was a cross-sectional study and causality cannot be proven.
Institute of Medicine, The Sahlgrenska Academy, Göteborg University, Göteborg, Sweden.
Björn
B
Fagerberg
Carl Johan
CJ
Behre
John
J
Wikstrand
Lillemor Mattsson
LM
Hultén
Johannes
J
Hulthe
D050197:Atherosclerosis / Q000097:blood*; D002097:C-Reactive Protein / Q000378:metabolism*; D005947:Glucose / Q000378:metabolism*; D006801:Humans; D007328:Insulin / Q000502:physiology*; D007333:Insulin Resistance / Q000502:physiology; D015850:Interleukin-6 / Q000097:blood; D008297:Male; D008875:Middle Aged; D047889:Receptors, Tumor Necrosis Factor, Type II / Q000097:blood; D012907:Smoking / Q000097:blood*; D014409:Tumor Necrosis Factor-alpha / Q000097:blood*
D007328:Insulin; D015850:Interleukin-6; D047889:Receptors, Tumor Necrosis Factor, Type II; D014409:Tumor Necrosis Factor-alpha; D002097:C-Reactive Protein; D005947:Glucose