Comment on the provisional report from the WHO
consultation
The recent provisional report on the definition, diagnosis and
classification from the WHO described 'the metabolic syn-
drome' as a 'major classification, diagnostic and therapeutic
challenge'-and we agree [lj.Adefinitionissorelyneededfor the
syndrome, as to date each publication describing the syndrome
uses its own definition of a component, and its own combination
and number of components to constitute the syndrome. If
identification of the syndrome is aimed at prevention or a
specific treatment of insulin resistance, a clear definition needs
to be provided, and the risk associated with the syndrome
evaluated in prospective studies. Our basic premise for the
definition is that it is a syndrome of mild anomalies which, in
combination, increase cardiovascular risk.
We suggest that because the syndrome includes non-
metabolic features, a more appropriate name would be the
'insulin resistance syndrome'. We also challenge the definition
proposed, namely, at least one of impaired glucose regulation or
insulin resistance and two or more of raised arterial pressure,
dyslipidaemia, central or overall obesity, microalbuminuria.
The syndrome was initially described with insulin resistance
as the central element [2]. We have as yet no evidence to believe
otherwise. The syndrome, as defined by the WHO, requires a
clamp study to be performed. As this definition is going to be
used mainly in epidemiology, and may in the future be used in
clinical practice, it is essential that readily available measures
are used. Given the relatively high negative correlation in
nondiabetic subjects between fasting insulin and insulin
sensitivity as measured in clamp studies [3], insulin resistant
individuals could be defined as the 25% of the population with
the highest insulin resistance or the highest fasting insulin
concentrations, providing the population under study could be
thought to be representative of the nondiabetic population.
Fasting insulin is so far the best available simple proxy for
insulin resistance but it could be replaced in the future by other
simple measurement(s) correlated with insulin resistance. As
there are different standards for assaying insulin, it is not
possible to propose a universal cut-off. If in future studies, this
definition is found to be useful in clinical practice, the
standardization of insulin assays will be mandatory.
The definition we propose is for nondiabetic individuals
only because there is no simple way to measure insulin
resistance in diabetic individuals. We suggest the syndrome is
defined by the presence of insulin resistance or fasting
hyperinsulinaemia (the highest 25%) and two of hypergly-
caemia (fasting plasma glucose & 6.1 mmol/l, but nondia-
betic); hypertension (systolic/diastolic blood pressures ^ 140/
90 mmHg or treated for hypertension); dyslipidaemia (trigly-
cerides > 2.0 mmol/l or HDL-cholesterol < 1.0 mmol/l or
treated for dyslipidaemia); central obesity (waist circumfer-
442
ence > 9 4 c m in men and s= 80cm in women). All of these
criteria must be measured before it is possible to evaluate the
presence of the syndrome. Hyperglycaemia should be defined
at fasting (fasting plasma glucose s= 6.1 mmol/l or impaired
fasting glucose) in nondiabetic individuals. Only the fasting
criteria are suggested to provide simpler criteria.
The recent report from the Second Joint Task Force of
Furopean and other Societies on Coronary Prevention [4] refer
to systolic/diastolic blood pressures of 140/90 mmHg as
being mild. The same report commented that fasting
triglycerides > 2.0 mmol/l (180mg/dl) and/or a HDL-choles-
terol < 1.0 mmol/l (40mg/dl) were 'markers of increased
coronary heart disease risk'.
For central obesity the proposed criteria used the waist-to-
hip ratio. The waist circumference is to be preferred as it is
simpler to measure and better correlated with intra-abdominal
visceral adipose tissue accumulation [5]. A recent study
provides cut-off values of 94 cm for men and 80 cm for
women as 'action levels' for prevention [6]. These limits could
be used pending further research in this area [7]. Overall
obesity, as measured by the body mass index, has not generally
been considered to be part of the syndrome and for that reason
it should be omitted.
For microalbuminuria, it has not been universally shown to
be linked with insulin concentrations [8,9], although a recent
article showed it to be linked to insulin resistance [10].
Microalbuminuria is not 'necessary for the recognition of the
condition' as stated by the WHO document and should be
omitted from the definition of the syndrome.
The final statement of the WHO consultation was that other
components 'have been described (e.g. hyperuricaemia, coa-
gulation disorders, raised PAI-1) but that they are not necessary
forthe recognition of the condition'. For practical purposes, and
so that the syndrome can be described in most epidemiological
studies and can be useful in identifying individuals at risk, it
should include a minimum number of components.
As this definition is simple, it could be used in most
epidemiological studies; it would at long last enable compar-
isons between studies, of the frequency and of the risk
associated with the insulin resistance syndrome.
B. Balkau and M. A. Charles for the European Group for
the Study of Insulin Resistance (EGIR)
European Group for the Study of Insulin Resistance,
Pisa, Italy
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