It has been suggested that a low grade inflammatory state could predispose for developing
insulin resistance and contribute to the development of
obesity and
type 2 diabetes.
Corticosteroid-binding globulin (
CBG), the main
plasma protein transport for
cortisol, has been shown to be negatively regulated by
insulin and
IL-6, at least in vitro, suggesting that
insulin resistance and
inflammation may both contribute to decreasing
CBG levels. In the present study we measured
CBG concentrations in a human healthy population and investigated the relationships of
CBG with anthropometric and
biochemical markers for
inflammation and/or
insulin resistance. The data showed that the mean serum
CBG level was significantly lower in males (n = 151) than in females (n = 113; 32.5 +/- 9.1 vs. 39.2 +/- 13.9 mg/liter; P < 0.0001). In both sexes serum
CBG levels were correlated negatively with age (r = -0.12; P = 0.04), body mass index (r = -0.31; P < 0.0001), waist to hip ratio (WHR; r = -0.39; P < 0.0001), systolic (r = -0.15; P < 0.01) and diastolic (r = -0.15; P = 0.01) blood pressures, and HOMA, an index of
insulin resistance (r = -0.12; P = 0.04). In addition, the
CBG concentration was negatively associated with serum
IL-6 concentrations (r = -0.23; P = 0.017) and with the soluble fraction of
TNFalpha receptors, soluble
TNF receptor 1 (sTNFR1; r = -0.35; P < 0.0001), and sTNFR2 (r = -0.56; P < 0.0001) in women. A stepwise regression analysis using
CBG as an independent variable showed that sex (P < 0.00001), body mass index (P = 0.0002), and HOMA (P = 0.0005), but not systolic blood pressure, diastolic blood pressure,
IL-6, sTNFR1, or sTNFR2, constituted significant independent factors that explained 21% of the
CBG variance (14%, 2%, and 5%, respectively). In a subsample of 120 men and 68 women, fasting serum free
cortisol (calculated as the ratio fasting
cortisol/
CBG) was significantly associated with WHR (r = 0.24; P = 0.001), systolic (r = 0.18; P = 0.01) and diastolic (r = 0.19; P = 0.007) blood pressures, and HOMA value (r = 0.20; P = 0.005), but not with BMI or age. BMI (P < 0.0001), free
cortisol (P = 0.003), and
CBG (P = 0.009), but not WHR and age, contributed to 20%, 6%, and 8%, respectively, of HOMA variance in women in a multiple regression analysis. In this model only BMI (P < 0.0001) independently contributed to HOMA variance in men. These findings support the hypothesis that the
CBG level is an interesting
indicator for both
insulin resistance and low grade
inflammation. Whether the decrease in
CBG levels is genetic by nature or directly associated to increased
insulin and/or
IL-6 merits further investigation. Nevertheless, because
CBG has been shown to be expressed by the adipose tissue, decreased
CBG could create locally increased
cortisol disposal, with no change in circulating
cortisol, and facilitate fat accumulation,
insulin resistance, and
type 2 diabetes.