Increased serum interleukin-18 concentration is associated with hypoadiponectinemia in obesity, independently of insulin resistance.

OBJECTIVE: Interleukin-18 (IL-18) is a cytokine with proinflammatory and proatherogenic properties, which might be associated with the development of insulin resistance. In contrast, adiponectin, a protein secreted by adipose tissue, might exert insulin-sensitizing and antiatherogenic effects. The aim of the present study was to analyze the association between serum IL-18 and adiponectin in lean and obese subjects, in relation to insulin resistance.
DESIGN: Cross-sectional study.
SUBJECTS: One hundred and thirty individuals, 62 lean (body mass index (BMI)<25 kg/m(2), 30 men and 32 women) and 68 with overweight or obesity (BMI>25 kg/m(2), 24 men and 44 women), with normal glucose tolerance and without concomitant diseases. MEASUREMENTS: Oral glucose tolerance test, euglycemic hyperinsulinemic clamp, serum concentrations of IL-18, IL-6, soluble tumor necrosis factor-alpha receptors and adiponectin.
RESULTS: Obese subjects had lower insulin sensitivity (M value, P=0.00029) and serum adiponectin (P=0.01) and higher levels of serum IL-18 (P=0.00055). Circulating IL-18 was negatively related to adiponectin (r=-0.31, P=0.00027) and insulin sensitivity (r=-0.33, P=0.00012). Subgroup analysis revealed that these associations were present in the obese (adiponectin, r=-0.38, P=0.0014; M, r=-0.29, P=0.016), but not in lean individuals (r=-0.17, P=0.18 and r=-0.20, P=0.12, respectively). Association of IL-18 with adiponectin remained significant after adjustment for other estimated parameters, including insulin sensitivity. Also, relationship between IL-18 and insulin sensitivity was independent of other estimated parameters.
CONCLUSION: Serum IL-18 is inversely related to serum adiponectin, independently of insulin resistance. The relationships of IL-18 with adiponectin and insulin sensitivity are influenced by the presence of overweight/obesity.