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Adrenocortical, Autonomic, and Inflammatory Causes of the Metabolic Syndrome: Nested Case-Control Study
Open accessAbstract
Background— The causes of metabolic syndrome (MS), which may be a precursor of coronary disease, are uncertain. We hypothesize that disturbances in neuroendocrine and cardiac autonomic activity (CAA) contribute to development of MS. We examine reversibility and the power of psychosocial and behavioral factors to explain the neuroendocrine adaptations that accompany MS. Methods and Results— This was a double-blind case-control study of working men aged 45 to 63 years drawn from the Whitehall II cohort. MS cases (n=30) were compared with healthy controls (n=153). Cortisol secretion, sensitivity, and 24-hour cortisol metabolite and catecholamine output were measured over 2 days. CAA was obtained from power spectral analysis of heart rate variability (HRV) recordings. Twenty-four-hour cortisol metabolite and normetanephrine (3-methoxynorepinephrine) outputs were higher among cases than controls (+ 0.49, +0.45 SD, respectively). HRV and total power were lower among cases (both −0.72 SD). Serum interleukin-6, plasma C-reactive protein, and viscosity were higher among cases (+0.89, +0.51, and +0.72 SD). Lower HRV was associated with higher normetanephrine output ( r =−0.19; P =0.03). Among former cases (MS 5 years previously, n=23), cortisol output, heart rate, and interleukin-6 were at the level of controls. Psychosocial factors accounted for 37% of the link between MS and normetanephrine output, and 7% to 19% for CAA. Health-related behaviors accounted for 5% to 18% of neuroendocrine differences. Conclusions— Neuroendocrine stress axes are activated in MS. There is relative cardiac sympathetic predominance. The neuroendocrine changes may be reversible. This case-control study provides the first evidence that chronic stress may be a cause of MS. Confirmatory prospective studies are required.
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“For instance, indices such as heart rate variability 27,28 and urinary normetanephrine 28 have suggested an increased sympathetic drive and its effects in MS patients.”
From Sympathetic Neural Activation in Nondiabetic Metabolic Syndrome and Its Further Augmentation by Hypertension (2004) · cites this paper as [27]
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Metadata
- Authors
- Brunner, E. J., Hemingway, H., Walker, B. R., Page, M., Clarke, P., Juneja, M., Shipley, M. J., Kumari, M., Andrew, R., Seckl, J. R., Papadopoulos, A., Checkley, S., Rumley, A., Lowe, G. D. O., Stansfeld, S. A., & Marmot, M. G.
- Affiliations
- Queen Mary University of London (GB)
- From the International Centre for Health and Society, Department of Epidemiology and Public Health, University College London, England; Endocrinology Unit (B.R.W., R.A., J.R.S.), Western General Hospital, University of Edinburgh, Scotland; Institute of Psychiatry (A.P., S.C.), Bethlem Royal Hospital, London, England; Department of Medicine (A.R., G.D.O.L.), Royal Infirmary, University of Glasgow, Scotland; and Department of Community Psychiatry (S.A.S.), Queen Mary and Westfield College, London,...
- ORCID
- Venue
- Circulation
- Published
- 2002-11-19
- Volume
- 106
- Issue
- 21
- Pages
- 2659-2665
- ISSN
- 0009-7322 (ISSN-L)
- 1524-4539
- OpenAlex
- W2104706609
- Cited by
- 539
- References
- 34
- Citations by year
- 2026: 3 · 2025: 12 · 2024: 9 · 2023: 14 · 2022: 6 · 2021: 18 · 2020: 9 · 2019: 10 · 2018: 18 · 2017: 19 · 2016: 31 · 2015: 20 · 2014: 22 · 2013: 33 · 2012: 29
- FWCI
- 11.28
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Circulation (publishedVersion)
- PubMed (publishedVersion)
- UCL Discovery (University College London) (submittedVersion)
- LSHTM Research Online (London School of Hygiene and Tropical Medicine) (submittedVersion)
- Funders
- John D. and Catherine T. MacArthur Foundation (HS06516)
- British Heart Foundation (HS06516)
- European Science Foundation
- Health and Safety Executive
- National Institutes of Health
- Agency for Healthcare Research and Quality (HS06516)
- Medical Research Council (HS06516)
- National Institute on Aging (AG 13196)
- National Heart, Lung, and Blood Institute (HS06516, HL36310, R01HL036310)
- Topics
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Heart Rate Variability and Autonomic Control
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adipokines, Inflammation, and Metabolic Diseases
- Keywords
- metabolic syndrome, neuroendocrine stress response, cardiac autonomic activity, heart rate variability, cortisol secretion, normetanephrine, interleukin-6, C-reactive protein, chronic stress, psychosocial factors, health behavior, reversibility, coronary disease risk
- MeSH terms
- Adrenal Cortex, Autonomic Nervous System, Blood Viscosity, C-Reactive Protein, Catecholamines, Double-Blind Method, Heart Rate, Humans, Hydrocortisone, Inflammation, Male, Middle Aged, Neurosecretory Systems, Normetanephrine, Psychology, Stress, Physiological, Cohort Studies, Interleukin-6, Case-Control Studies, Coronary Restenosis, Metabolic Syndrome
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