Psychoneuroendocrine aspects on the metabolic syndrome. A population-based study of middle-aged men

Abstract

Background: Abdominal obesity is associated with prevalent and serious diseases. The causes of abdominal obesity are most likely to be both genetic and environmental. Among the latter factors a hypersensitive hypothalamic-pituitary-adrenal (HPA) axis followed by an inadequate cortisol secretion has been suggested.Aims: To investigate the effect of psychological distress on abdominal obesity and the regulation of cortisol secretion. Furthermore, to examine the peripheral consequences of an inadequate cortisol secretion, by means of newly developed techniques for the assessment of cortisol, and to evaluate the impact of the HPA axis activity on established risk factors for cardiovascular disease (CVD), Type 2 diabetes mellitus and stroke.Subjects and Methods: A population of 1302 men born 1944 was selected from the city of Göteborg, Sweden. They were providing responses to a questionnaire and self-measurements of height, weight, and circumferences over the waist and hips. Subgroups of the waist/hip circumference ratio (WHR) (n=284) were then invited for an examination including measurements of anthropometry (body mass index, BMI, kg/m2, WHR and abdominal sagittal diameter, D), hormones (testosterone and insulin-like growth factor I, IGF-I), metabolism (overnight fasting values of insulin, glucose, triglycerides, total-, LDL- and HDL-cholesterol), and circulation (systolic and diastolic blood pressures and heart rate). Furthermore, salivary cortisol concentrations were determined on repeated (n=7) occasions over a random working day, and perceived stress reported in parallel. A standardised lunch was used as a physiological challenge. A low dose (0.5 mg) dexamethasone suppression test was also performed.Results: The WHR showed significant and independent relationships to the use of psycho-pharmacological drugs, depressive symptoms and sleep disturbances. A blunted dexamethasone suppression of cortisol was found in a subgroup of men with anxiety and depression and elevated BMI, WHR, and D. In addition, with an inadequate cortisol secretory pattern, stress-related cortisol secretion showed strong relationships to elevated BMI, WHR and D, all metabolic measurements except HDL, which was low. Blood pressure and heart rate were elevated, and testosterone and IGF-I were low. After stimulation of cortisol secretion by food intake, positive associations were found with BMI, waist and hip circumferences, WHR and D, as well as insulin, glucose and the insulin/glucose ratio, total and LDL cholesterol, blood pressures and heart rate. Furthermore, under the influence of such an abnormal cortisol secretory pattern, the risk factors for CVD, Type 2 diabetes and stroke congregated into one distinct, strongly intercorrelated cluster. In contrast, a normal cortisol secretory pattern was associated with low values of total and LDL cholesterol as well as blood pressures, and high IGF-I. Conclusions: The results suggest that the function of the HPA axis is of fundamental importance for anthropometric, endocrine, metabolic and hemodynamic factors. When perturbed, the development of abdominal obesity, endocrine abnormalities, insulin resistance and hypertension follow, leading to serious diseases. This syndrome is based on environmental pressures in genetically vulnerable subjects.