Comment on the provisional report from the WHO consultation

The recent provisional report on the de®nition, diagnosis and classi®cation from the WHO described `the metabolic syndrome' as a `major classi®cation, diagnostic and therapeutic challenge'±andweagree[1].Ade®nitionissorelyneededforthe syndrome, as to date each publication describing the syndrome usesitsownde®nitionofacomponent,anditsowncombination and number of components to constitute the syndrome. If identi®cation of the syndrome is aimed at prevention or a speci®c treatment of insulin resistance, a clear de®nition needs to be provided, and the risk associated with the syndrome evaluated in prospective studies. Our basic premise for the de®nition is that it is a syndrome of mild anomalies which, in combination, increase cardiovascular risk. We suggest that because the syndrome includes nonmetabolic features, a more appropriate name would be the `insulin resistance syndrome'. We also challenge the de®nition proposed,namely,atleastoneofimpairedglucoseregulationor 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 de®ned by the WHO, requires a clamp study to be performed. As this de®nition 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 de®ned 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 de®nition is found to be useful in clinical practice, the standardization of insulin assays will be mandatory. The de®nition 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 de®ned by the presence of insulin resistance or fasting hyperinsulinaemia (the highest 25%) and two of hyperglycaemia (fasting plasma glucose > 6.1 mmol/l, but nondiabetic); hypertension (systolic/diastolic blood pressures > 140/ 90 mmHg or treated for hypertension); dyslipidaemia (triglycerides > 2.0 mmol/l or HDL-cholesterol < 1.0 mmol/l or treated for dyslipidaemia); central obesity (waist circumference > 94 cm in men and > 80 cm in women). All of these criteria must be measured before it is possible to evaluate the presence of the syndrome. Hyperglycaemia should be de®ned at fasting (fasting plasma glucose > 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 European 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 (180 mg/dl) and/or a HDL-cholesterol < 1.0 mmol/l (40 mg/dl) were `markers of increased coronary heart disease risk'. For central obesity the proposed criteria used the waist-tohip 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 de®nition of the syndrome. The ®nal statement of the WHO consultation was that other components `have been described (e.g. hyperuricaemia, coagulationdisorders, raisedPAI-1)but that theyarenotnecessary fortherecognitionofthecondition'.Forpracticalpurposes,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 de®nition is simple, it could be used in most epidemiological studies; it would at long last enable comparisons between studies, of the frequency and of the risk associated with the insulin resistance syndrome.