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