The insulin resistance syndrome and the binding capacity of cortisol binding globulin (CBG) in men and women

BACKGROUND Both insulin resistance and cortisol binding globulin (CBG) capa city have been found to correlate with plasma free fatty acid (FFA) concent ration. OBJECTIVE To examine the changes in CBG binding with varying degrees of ins ulin resistance and plasma FFA levels. SUBJECTS AND METHODS Anthropometric parameters, serum cortisol levels, plas ma CBG, CBG binding and insulin sensitivity (using the frequently sampled i ntravenous glucose tolerance test with minimal model analysis) were measure d in a group of 38 healthy subjects (19 men, mean age 36.2 +/- 1.9; body ma ss index (BMI) 28.8 +/- 1.2, range 22.2-35.7), and 19 women, age 34.9 +/- 1 .4; BMI 28.1 +/- 0.8, range 19-37.9)]. RESULTS Plasma CBG levels did not differ between men and women. In men, CBG binding was associated with several parameters of the insulin resistance s yndrome, including area under the curve for glucose during an oral glucose tolerance test (MBG, r = 0.45, P = 0.04), fasting insulin (r = 0.66, P = 0. 002), plasma triglycerides (r = 0.75, P < 0.0001), VLDL-triglycerides (r = 0.59, P = 0.007), fasting FFA (r = 0.72, P = 0.002), uric acid (r = 0.57 (P = 0.01) and insulin sensitivity (S-I, r = - 0.58, P = 0.008). Free cortiso l (estimated as the ratio of cortisol to CBG) was not associated with waist -to-hip ratio (WHR) or parameters of insulin sensitivity. In contrast to me n, CBG binding was not associated with MBG, fasting insulin, plasma triglyc erides, VLDL-triglycerides, FFA, uric acid or S-I (all P = NS) in women. Se rum free cortisol, however, correlated positively with WHR (r = 0.62, P = 0 .02) and negatively with S-I (r = - 0.68, P = 0.01) in obese women. A multi ple linear regression to predict CBG binding was constructed, with plasma C BG concentration and insulin sensitivity as independent variables. In this model, only S-I entered the equation at a statistically significant level ( P = 0.0012) contributing to 52% of the variance in CBG binding in men. When plasma FFA levels were added to the model, both S-I (P = 0.04) and FFA lev els (P = 0.039) contributed to 66% of the variance of CBG binding in men. I n women, both plasma CBG concentration (P = 0.0005) and insulin sensitivity (P = 0.047) entered the equation at a statistically significant level, con tributing to 60% of the variance in CBG binding. When plasma FFA levels wer e added to the model, only plasma CBG concentration (P = 0.043) was found t o significantly contribute to 38% of the variance in CBG binding. The latte r finding suggests that FFA levels constituted a confounding variable in th e association between S-I and CBG binding in women. CONCLUSIONS Both plasma free fatty acid and insulin sensitivity influence c ortisol binding globulin binding capacity in men. Whether cortisol binding globulin binding is a factor implicated in the pathophysiology of insulin r esistance or represents an adaptative tool in this situation awaits further studies.