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.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Mentored Patient-Oriented Research Career Development Award (K23)
Project #
1K23DK071565-01
Application #
6956626
Study Section
Diabetes, Endocrinology and Metabolic Diseases B Subcommittee (DDK)
Program Officer
Hyde, James F
Project Start
2005-07-05
Project End
2010-06-30
Budget Start
2005-07-05
Budget End
2006-06-30
Support Year
1
Fiscal Year
2005
Total Cost
$133,442
Indirect Cost
Name
Johns Hopkins University
Department
Public Health & Prev Medicine
Type
Schools of Public Health
DUNS #
001910777
City
Baltimore
State
MD
Country
United States
Zip Code
21218
Champaneri, Shivam; Xu, Xiaoqiang; Carnethon, Mercedes R et al. (2013) Diurnal salivary cortisol is associated with body mass index and waist circumference: the Multiethnic Study of Atherosclerosis. Obesity (Silver Spring) 21:E56-63
Champaneri, Shivam; Xu, Xiaoqiang; Carnethon, Mercedes R et al. (2012) Diurnal salivary cortisol and urinary catecholamines are associated with diabetes mellitus: the Multi-Ethnic Study of Atherosclerosis. Metabolism 61:986-95
Golden, Sherita Hill; Wand, Gary S; Malhotra, Saurabh et al. (2011) Reliability of hypothalamic-pituitary-adrenal axis assessment methods for use in population-based studies. Eur J Epidemiol 26:511-25
Champaneri, Shivam; Wand, Gary S; Malhotra, Saurabh S et al. (2010) Biological basis of depression in adults with diabetes. Curr Diab Rep 10:396-405
Kalyani, Rita Rastogi; Franco, Manuel; Dobs, Adrian S et al. (2009) The association of endogenous sex hormones, adiposity, and insulin resistance with incident diabetes in postmenopausal women. J Clin Endocrinol Metab 94:4127-35
Golden, Sherita Hill; Lazo, Mariana; Carnethon, Mercedes et al. (2008) Examining a bidirectional association between depressive symptoms and diabetes. JAMA 299:2751-9
Mezuk, Briana; Eaton, William W; Golden, Sherita Hill et al. (2008) The influence of educational attainment on depression and risk of type 2 diabetes. Am J Public Health 98:1480-5
Golden, Sherita Hill; Dobs, Adrian S; Vaidya, Dhananjay et al. (2007) Endogenous sex hormones and glucose tolerance status in postmenopausal women. J Clin Endocrinol Metab 92:1289-95
Golden, Sherita H; Selvin, Elizabeth; Cunningham, Kayla E (2007) Glycaemic status and cardiovascular disease in type 2 diabetes mellitus: re-visiting glycated haemoglobin targets for cardiovascular disease prevention. Diabetes Obes Metab 9:792-8
Golden, Sherita Hill; Malhotra, Saurabh; Wand, Gary S et al. (2007) Adrenal gland volume and dexamethasone-suppressed cortisol correlate with total daily salivary cortisol in African-American women. J Clin Endocrinol Metab 92:1358-63

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