Cortisol, obesity, and the metabolic syndrome: a cross-sectional study of obese subjects and review of the literature

Abstract

Objective: Circulating cortisol and psychosocial stress may contribute to the pathogenesis of obesity and metabolic syndrome (MS). To evaluate these relationships, a cross-sectional study of 369 overweight and obese subjects and 60 healthy volunteers was performed and reviewed the previous literature.

Design and methods: Overweight and obese subjects had at least two other features of Cushing's syndrome. They underwent measurements representing cortisol dynamics (24 h urine cortisol excretion (UFC), bedtime salivary cortisol, 1 mg dexamethasone suppression test) and metabolic parameters (BMI, blood pressure (BP); fasting serum triglycerides, HDL, insulin, and glucose). Subjects also completed the Perceived Stress Scale (PSS). UFC, salivary cortisol, and weight from 60 healthy volunteers were analyzed.

Results: No subject had Cushing's syndrome. UFC and dexamethasone responses were not associated with BMI or weight. However, salivary cortisol showed a trend to increase as BMI increased (P < 0.0001), and correlated with waist circumference (WC) in men (rs = 0.28, P = 0.02) and systolic BP in women (rs = 0.24, P = 0.0008). Post-dexamethasone cortisol levels were weak to moderately correlated with fasting insulin (rs = -0.31, P = 0.01) and HOMA-IR (rs = -0.31, P = 0.01) in men and systolic (rs = 0.18, P = 0.02) and diastolic BP (rs = 0.20, P = 0.009) in women. PSS results were higher in obese subjects than controls, but were not associated with cortisol or metabolic parameters. As expected, WC correlated with fasting insulin, HOMA-IR, and systolic BP (adjusted for BMI and gender; P < 0.01). Literature showed inconsistent relationships between cortisol and metabolic parameters.

Conclusion: Taken together, these data do not support a strong relationship between systemic cortisol or stress and obesity or MS.

Figure 1

24 h urine free cortisol (UFC) versus BMI in individual subjects (healthy volunteers and overweight and obese study group). The solid line represents the upper reference limit.

Figure 2

Salivary cortisol (log scale) versus BMI in individual subjects (healthy volunteers and overweight and obese study group). The solid line represents the upper reference limit.

Figure 3

Figure 3a. 24 h urine free cortisol (UFC) levels in subjects with and without metabolic syndrome (MS; using modified ATP III criteria). Unfilled circles (○) represent individuals without MS and filled circles (●) represent those with MS. Upper reference limit (solid line) for UFC is 45 ug/24 h (124 nmol/24 h). Figure 3b. Salivary cortisol levels in subjects with and without MS (using modified ATP III criteria for metabolic syndrome). Unfilled circles (○) represent individuals without MS and filled circles (●) represent those with MS. Upper reference limit (solid line) for salivary cortisol is < 100 ng/dl (2.8 nmol/l). Two patients’ salivary cortisol levels of 1300 and 643 ng/dl are not shown.

Figure 3

Figure 3a. 24 h urine free cortisol (UFC) levels in subjects with and without metabolic syndrome (MS; using modified ATP III criteria). Unfilled circles (○) represent individuals without MS and filled circles (●) represent those with MS. Upper reference limit (solid line) for UFC is 45 ug/24 h (124 nmol/24 h). Figure 3b. Salivary cortisol levels in subjects with and without MS (using modified ATP III criteria for metabolic syndrome). Unfilled circles (○) represent individuals without MS and filled circles (●) represent those with MS. Upper reference limit (solid line) for salivary cortisol is < 100 ng/dl (2.8 nmol/l). Two patients’ salivary cortisol levels of 1300 and 643 ng/dl are not shown.

Figure 4

Median Perceived Stress Scale scores (PSS) in women and men with (gray bar), without (white bar) metabolic syndrome (using modified ATP III criteria), and the total group (gradient bar); Error bars represent inter-quartile range (IQR; 25^th percentile, 75^th percentile); *P< 0.05, PSS in women with vs. without metabolic syndrome; **P = 0.005, PSS in women vs. men.