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) capacity have been found to correlate with plasma free fatty acid (FFA) concentration. OBJECTIVE: To examine the changes in CBG binding with varying degrees of insulin resistance and plasma FFA levels. SUBJECTS AND METHODS: Anthropometric parameters, serum cortisol levels, plasma CBG, CBG binding and insulin sensitivity (using the frequently sampled intravenous glucose tolerance test with minimal model analysis) were measured in a group of 38 healthy subjects (19 men, mean age 36.2 ± 1.9; body mass 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 syndrome, 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(l), r=-0.58, P=0.008). Free cortisol (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 men, CBG binding was not associated with MBG, fasting insulin, plasma triglycerides, VLDL- triglycerides, FFA, uric acid or S(l) (all P = NS) in women. Serum free cortisol, however, correlated positively with WHR (r=0.62, P=0.02) and negatively with S(l) (r=-0.68, P=0.01) in obese women. A multiple linear regression to predict CBG binding was constructed, with plasma CBG concentration and insulin sensitivity as independent variables. In this model, only S(l) 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(l) (P=0.04) and FFA levels (P=0.039) contributed to 66% of the variance of CBG binding in men. In women, both plasma CBG concentration (P=0.0005) and insulin sensitivity (P=0.047) entered the equation at a statistically significant level, contributing to 60% of the variance in CBG binding. When plasma FFA levels were added to the model, only plasma CBG concentration (P=0.043) was found to significantly contribute to 38% of the variance in CBG binding. The latter finding suggests that FFA levels constituted a confounding variable in the association between S, and CBG binding in women. CONCLUSIONS: Both plasma free fatty acid and insulin sensitivity influence cortisol binding globulin binding capacity in men. Whether cortisol binding globulin binding is a factor implicated in the pathophysiology of insulin resistance or represents an adaptative tool in this situation awaits further studies.