Chronic stress at work and the metabolic syndrome: prospective study

Central Obesity and Weight Gain May Confound the Relationship Between Chronic Stress at Work and the Metabolic Syndrome

10 March 2006

Chandola and colleagues (1) have amassed an intriguing dataset to permit hypotheses to be generated around the relationships between occupational grade, work stress and cardiovascular disease. They have, however, fallen into the trap of confusing a clinical clustering of risk factors, the Metabolic Syndrome, with a physiological construct.

The associations between dyslipidaemia, hypertension, glucose intolerance and central obesity have been recognised for decades. In 1988, Reaven proposed insulin resistance as an underlying mechanism for this clustering, which he termed Syndrome X (2). However he excluded obesity from the component parts of this Syndrome because, as he has recently pointed out (3), it is not a consequence of insulin resistance, but only increases its likelihood. The definition of Metabolic Syndrome employed by Chandola et al is that of the NCEP-ATP III (4), a Panel concerned with clinical identification of subjects at high cardiovascular risk. The Panel report notes that excess body fat (particularly abdominal obesity) and physical inactivity are important determinants of the cluster, and major targets of treatment. There is, then, a danger of confusing aetiology with outcome by the inclusion of abdominal obesity as one of the three risk factors used to define the presence of the Metabolic Syndrome.

Previous studies from Brunner, Marmot and colleagues, based on this same Whitehall II cohort, have shown cross-sectional relationships between employment grade and central obesity (5), and longitudinal relationships between work stress and weight gain over a five year follow-up (6). It seems likely, then, that at least some of the work stress-Metabolic Syndrome relationship in the current study is simply the consequence of greater weight gain in people subject to chronic work stress.

The Whitehall II study nevertheless provides a potentially valuable resource for a more rigorous exploration of mechanisms. The dominant paradigm to explain the Metabolic Syndrome is that of low-grade inflammation (7), consequent upon generation of adipocytokines, particularly from visceral fat (8), which may also account for both insulin resistance and vascular disease (9). While longitudinal changes in body-mass index are likely to represent the consequences of positive energy balance (greater calorie intake or reduced physical activity), the relationship between employment grade or work stress and central distribution of fat is more intriguing. Thus, while in part this may be consequent upon differences in physical activity or in smoking, the potential role of the hypothalamo-pituitary-adrenal (HPA) axis is worth exploring. More sophisticated modelling might permit testing the role of adipose tissue-generated cytokines in activating this HPA axis (10), and in the autonomic nervous system changes which this group has also linked to the Metabolic Syndrome (11). However, any independent relationship of employment grade or work stress with components of the Metabolic Syndrome other than obesity will require rigorous adjustment for the confounding influence of body fat mass.

References

1. Chandola T, Brunner E and Marmot M. Chronic stress at work and the metabolic syndrome: prospective study. BMJ 2006; 332: 521-525.

2. Reaven GM. Role of insulin resistance in human disease. Diabetes 1988; 37: 1595-1607.

3. Reaven G. Insulin resistance, type 2 diabetes mellitus and cardiovascular disease – the end of the beginning. Circulation 2005; 112: 3030-3032.

4. Expert Panel on Detection, Evaluation and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III). Executive Summary of the Third Report of the National Cholesterol Education Program (NCEP). JAMA 2001; 285: 2486-2497.

5. Brunner EJ, Marmot MG, Nanchahal K, Shipley MJ, Stansfield SA, Juneja M and Alberti KGMM. Social inequality in coronary risk: central obesity and the metabolic syndrome. Evidence from the Whitehall II study. Diabeteologia 1997; 40: 1341-1349.

6. Kivimäki M, Head J, Ferrie JE, Shipley MJ, Brunner E, Vahtera J and Marmot MG. Work stress, weight gain and weight loss: evidence for bidirectional effects of job strain on body mass index in the Whitehall II study. Int J Obes advance online publication, 17 January 2006; doi:10.1038/sj.ijo.0803229.

7. Cai D, Yuan M, Frantz DF, Melendez PA, Hansen L, Lee J and Shoelson SE.Local and systemic insulin resistance resulting from hepatic activation of IKK-β and NF-κβ. Nature Medicine 2005; 11: 183-190.

8. De Luca C and Olefsky JM. Stressed out about obesity and insulin resistance. Nature Medicine 2006; 12: 41-42.

9. Yudkin JS, Stehouwer CDA, Emeis JJ and Coppack SW. C-reactive protein in healthy subjects: association with obesity, insulin resistance, and endothelial dysfunction. Arterioscleros Thromb Vasc Biol 1999; 19: 972-978.

10. Yudkin JS, Kumari M, Humphries S and Mohamed-Ali V on behalf of the University College London Interleukin-6 Group. Inflammation, obesity, stress and coronary heart disease: is interleukin-6 the link? Atherosclerosis 2000; 148: 209-214.

11. Hemingway H, Shipley M, Brunner E, Britton A, Malik M and Marmot M. Does autonomic function link social position to coronary risk? Circulation 2005; 111: 3071-3077.

Competing interests: None declared

Competing interests: None declared

John S Yudkin, Professor of Medicine

University College London, Holborn Union Building, Archway Campus, Highgate Hill, London N19 5LW

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