The association of cortisol excretion with weight and metabolic parameters in nondiabetic patients with morbid obesity

Introduction: Cortisol is involved in the regulation of gluconeogenesis and glucose utilization. In morbid obesity (MO), the association of cortisol excretion with metabolic parameters is not well-characterized. In our study, we evaluated cortisol excretion in nondiabetic subjects with MO and its effect on glucose metabolism. Methods: We included 1,249 nondiabetic patients with MO (79.8% females, mean BMI 44.9 ± 6.5 kg/m2, mean age 38 ± 11 years). Anthropometric data and cardiovascular risk factors were assessed, and an oral glucose tolerance test for calculation of insulin resistance was performed. Cortisol excretion was assessed on 2 consecutive days (24 h urine specimens). Results: Regarding cortisol excretion, patients were divided into 3 tertiles (urinary cortisol <=51.6, >51.6 and <117.6, and >=117.6 ?g/24 h, respectively). Patients in the highest tertile were younger (p = 0.003), more obese (BMI: p = 0.040), had lower diastolic blood pressure ([DBP]; p = 0.012), lower total (p = 0.032) and LDL cholesterol (p = 0.021), fasting (p = 0.049) and 2-h glycemia (p = 0.028), 2-h insulinemia (p = 0.020), and HbA1c (p < 0.001), and a higher estimated glomerular filtration rate (eGFR) (p < 0.001). The glucose (p < 0.001) and insulin (p = 0.011) area under the curve (AUC) were also lower. Urinary cortisol excretion adjusted for age, sex, and eGFR was positively correlated with body weight (BW, beta = 0.076, p = 0.004) and overall glucose tolerance (oral disposition index, beta = 0.090, p = 0.011), and negatively with HbA1c (beta = -0.179, p < 0.001), 2-h glycemia (beta = -0.075, p = 0.032), AUC glucose (beta = -0.103, p = 0.002), and DBP (beta = -0.139, p < 0.001). HbA1c, BW, and DBP remained significant after multivariable analysis. Discussion/Conclusion: Despite being more obese, patients with higher cortisol excretion have a more favorable metabolic profile. These results deserve further attention regarding the respective mechanisms.