Although chronic psychological stress (e.g. depression) and physiological stress (e.g. sleep disordered breathing) are associated with the risk of both type 2 diabetes and cardiovascular disease, the mechanism remains unclear. Neuroendocrine changes induced by these stressors, specifically activation of the hypothalamic-pituitary-adrenal (HPA) axis, might provide a unifying explanation. We hypothesize that salivary cortisol represents a feasible approach for assessment of HPA axis activity in large-scale epidemiological cohort and intervention studies, that increased activity of the HPA axis is positively associated risk factors for type 2 diabetes and cardiovascular disease, and that this is the mechanism by which chronic psychological and physiological stressors lead to these outcomes. To test these hypotheses, we propose a study with the following specific aims: 1.) Confirm findings from our preliminary data that 8 am salivary cortisol is an acceptable measure of HPA axis activity such that it can be substituted for 24-hour urine free cortisol (UFC) in assessing glucocorticoid exposure. 2.) Determine the cross-sectional association of HPA axis activity to measures of psychological stress, metabolic risk factors, and sleep disordered breathing, as a measure of physiological stress. 3.) Determine the effect of moderate exercise on HPA axis activity and to determine whether the beneficial effects of exercise on blood pressure, cardiac and peripheral vascular function, physical fitness, body composition, lipids, and glycemic control are mediated by changes in cortisol levels and/or cortisol variability after 6 months. To accomplish these aims, we will exploit existing research infrastructure at Hopkins including the Inpatient GCRC (which is already supporting a pilot study of psychological stress, HPA axis activity, and metabolic risk factors in African-American women) and we will also incorporate salivary cortisol assays into 3 on-going NIH-funded Hopkins studies: a population-based study of carotid atherosclerosis, a study of sleep disordered breathing, and an exercise intervention study.
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