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

Abstract

Circulating cortisol and psychosocial stress may contribute to the pathogenesis of obesity and metabolic syndrome. To evaluate these relationships, we performed a cross-sectional study of 369 overweight and obese subjects and 60 healthy volunteers and reviewed the previous literature. Overweight and obese subjects had at least two other features of Cushing’s syndrome. They underwent measurements representing cortisol dynamics (24h 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. 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. Taken together, these data do not support a strong relationship between systemic cortisol or stress and obesity or metabolic syndrome.

Hypothalamic-pituitary-adrenal axis dysregulation and cortisol activity in obesity: A systematic review

“…Despite these findings however, another study found that after 1.0 mg of dexamethasone, cortisol concentrations in serum were not associated with BMI (Abraham et al, 2013), and similarly, a sample of females found no relationship with any obesity measure and inhibition of cortisol secretion after 1.0 mg dexamethasone administration (Mårin et al, 1992). This study, however, did not measure or account for abdominal measures of obesity.…”

“…Given the strong pattern of findings and the fact that some of the literature has attempted to examine generalized and abdominal obesity independently, the GRADE rating of the the strength of this evidence would be "moderate-to-high." This consistent pattern of findings is of marked importance in this population as obese individuals tend to experience more repeated stressors (Abraham et al, 2013;Nyberg et al, 2012). In light of this evidence, high prevalence of life stressors paired with an overactive cortisol response may in fact perpetuate obesity and HPA-related diseases.…”

“…Using a single-time point proxy, a study of obese men found that plasma cortisol at 1230 h was inversely related to BMI (Rask et al, 2001), perhaps suggesting more marked flattening of the slope at higher BMIs. Another study found a strong relationship wherein salivary cortisol output at bedtime tended to increase with BMI, indicating that a negative diurnal rhythm was not allowing for cortisol to reach a sufficiently low point at the end of the day (Abraham et al, 2013). This measure correlated with waist circumference, but only in men, and in line with the majority of the existing literature, the study did not analyze obesity types individually.…”

“…In a meta-analysis of 13 studies including over 160,000 workers, job strain was found to be positively related to body mass index (BMI) both cross-sectionally and longitudinally (Nyberg et al, 2012). This is particularly relevant to obesity, as recent findings show that that obese individuals tended to report higher perceived stress (Abraham et al, 2013). Physiologically, increased cortisol concentrations have been causally linked to fat accumulation and weight gain, as glucocorticoids promote conversion of preadipocytes to mature adipocytes (for a review, see Peckett et al, 2011).…”

Metabolic and Hormonal Response to a Feed‐challenge Test in Lean and Overweight Dogs

“…Similarly, night‐time urine cortisol was higher in obese human patients than in normal weight controls 13. Although a hypothetical role of glucocorticoids in human obesity has been suggested,13 the role is debated with inconclusive results regarding the assumed positive relationship between cortisol secretion and body fat content 39. Increased sensitivity along the hypothalamic‐pituitary‐adrenal axis as well as peripheral alterations of cortisol metabolism could play a role in the pathophysiology of abdominal obesity 13.…”