Background: It has been shown previously that morning cortisol levels decline after oral glucose, but no report has been published regarding the changes in serum cortisol in relation to insulin sensitivity or degree of obesity.
Subjects and design: We studied the effects of oral glucose during a standard oral glucose tolerance test on cortisol levels in 7 obese subjects (body mass index (BMI) 29.7 +/- 3.3 kg/m2) and in 8 control subjects (BMI 24.9 +/- 3.2 kg/m2). Cortisol concentrations were normalized to time 0 because of wide between subject variation. On another day, a frequently sampled intravenous glucose tolerance test with minimal model analysis was performed, obtaining the insulin sensitivity index (SI). Anthropometric measurements included different skinfolds and bioelectric impedance.
Results: The waist-to-hip ratio (WHR) was similar between the 2 groups, but abdominal skinfold was significantly higher in the obese group (OG) (158.8 +/- 42.9 vs. 113.6 +/- 27.7, P = 0.03). Fat mass, percentage of fat mass, triceps and subscapular skinfolds, systolic and diastolic blood pressure, VLDL-cholesterol, total triglycerides and VLDL-triglycerides were slightly higher in the obese group (OG). Area under the curve for glucose (AUCg) after OGTT was also significantly higher in OG (9.9 +/- 2.4 vs. 7.1 +/- 0.5 mmol/l, P = 0.02) in contrast to area under the curve for insulin (102 +/- 60 vs. 73.8 +/- 26.7 mU/l, P = NS), or glucose effectiveness (0.015 +/- 0.004 vs. 0.015 +/- 0.009 min-1, P = NS). Subjects with the highest WHR of both groups exhibited a greater cortisol suppression (56 +/- 0.09 vs. 41 +/- 0.17, P = 0.05). Normalized serum cortisol after OGTT was significantly lower from minute 60 to 120 in the OG (P = 0.001, 0.003 and 0.01 at 60, 90 and 120 minutes, respectively). The maximal cortisol suppression was 59.2% in the OG in comparison with 43% in the control group (P = 0.027). This maximal cortisol suppression correlated weakly with the maximal insulin response after oral glucose (r = 0.49, P = 0.07). In a multiple linear regression analysis, with maximal cortisol suppression as dependent variable, both BMI (P = 0.03) and SI (0.02) contributed to the variance of maximal cortisol suppression (R2 = 0.40).
Conclusion: We show that differences in cortisol decline are at least partially attributed to differences in insulin sensitivity and to differences in abdominal fat. This abdominal-related decrease of cortisol might support the concept that the increased visceral adipose tissue mass with a high density of glucocorticoid receptors enhances the metabolism of cortisol. Perhaps the subjects with higher abdominal fat or insulin resistance are prone to lower cortisol levels after carbohydrate-rich intakes in the morning. These lower cortisol levels, behaving as a positive feed-back signal, might generate higher ACTH and cortisol responses after protein-rich meals at mid-day.