In experimental models, adiponectin improves and tumor necrosis factor alpha (TNF-alpha) impairs insulin action, and the expression of these adipocytokines seems to have a reciprocal regulation. The aim was to examine whether in a cross-sectional study, associations supporting this concept may be found in 58-year-old clinically healthy men, and also the relation to C-reactive protein (CRP). In 102 men, euglycemic hyperinsulinemic clamp was used to assess glucose infusion rate (GIR). Total body fat (dual-energy x-ray absorptiometry), plasma adiponectin (radioimmunoassay), TNF-alpha, and CRP (enzyme-linked immumosorbent assay) were measured. Adiponectin correlated positively to GIR (r = 0.33, P <.001) and negatively to total fat mass (r = -0.29, P = .004), whereas TNF-a showed reverse associations (r = -0.31, P <.01, and r = 0.31, P <.01). Adiponectin and TNF-a were negatively correlated (-0.28, P = .006). An interaction term (TNF-alpha/adiponectin ratio) and body fat together explained 31.3% (P <.001) in GIR variability. The odds ratio for having insulin resistance was 9.3 (95% CI, 2.2-38.9) in subjects with TNF-alpha values above and adiponectin levels below the median, as compared to subjects with TNF-alpha values below and adiponectin levels above the median. Total fat and TNF-alpha, but not adiponectin, were significantly associated with log CRP (R-2 = 20%, P <.001). In conclusion, this study in man showed that plasma adiponectin and TNF-alpha were independently and reversely associated with insulin resistance. C-reactive protein levels were related to TNF-alpha and obesity. (c) 2005 Elsevier Inc. All rights reserved.