Should we dump the metabolic syndrome?: Yes

Abstract

The number of people with the metabolic syndrome is rising alongside obesity. Nevertheless, Edwin Gale believes the diagnosis has little practical value. George Alberti and P Z Zimmet, however, think it increases the detection of people at high risk of diabetes and heart disease

Type 2 diabetes and lesser degrees of glucose intolerance are associated with insulin resistance, central obesity, hypertension, and dyslipidaemia. The term metabolic syndrome describes the same constellation, with or without glucose intolerance. Although these associations are well established, their pathophysiological basis remains unclear, and no unifying feature has emerged. Attempts have been made to assemble the various features of the metabolic syndrome into a single all-purpose definition, for which diagnostic, prognostic, and therapeutic value has been claimed. Diagnosis of the metabolic syndrome is redundant in those who already have diabetes and adds nothing to the management of those who do not.

Unclear definition

A cluster of clinical features constitutes a syndrome, but attempts to define the metabolic syndrome as a clinical entity have been hampered by the lack of an agreed unifying feature. The grouping was first described in patients with type 2 diabetes,¹ and the wider concept of a “metabolic” syndrome arose when Gerald Reaven suggested that the common factor was insulin resistance rather than diabetes.² Insulin resistance is, however, unsatisfactory as a core feature, for it cannot be defined or measured easily and is inconsistently related to the individual features of the syndrome.³

Expert panels have made various attempts to establish a working definition using different scoring systems.^{4 5} The endeavour was complicated by uncertainty about which associated features to include, what thresholds to set, and what exactly the experts were trying to achieve. The schemes that emerged have proved useful for statistical analysis and epidemiological comparison, but not for clinicians, who hardly ever record the diagnosis.⁶

The most recent definition, proposed by an expert committee of the International Diabetes Federation, bases the syndrome around a new core feature, central obesity, and is intended for clinical use (box).⁴ Representatives of the American Diabetes Association and the European Association for the Study of Diabetes have, however, argued that any such attempt is premature.⁵ This is not a turf war: the confrontation reflects genuine perplexity within the diabetes community. One party maintains that a working definition is needed to resolve existing confusion; the other party argues that an inadequate definition merely adds to it.

International Diabetes Federation definition of metabolic syndrome⁴

Presence of central obesity—Waist circumference varies with ethnicity (see bmj.com). If body mass index is >30 central obesity can be assumed

Plus any two of the following:

• Triglyceride concentration ≥1.7 mmol/l or specific treatment for this lipid abnormality

• High density lipoprotein cholesterol <1.03 mmol/l in men, <1.29 mmol/l in women, or specific treatment for hypercholesterolaemia

• Systolic blood pressure ≥130 mm Hg or diastolic ≥ 85 mmol/l, or treatment for hypertension

• Fasting plasma glucose ≥5.6 mmol/l or previously diagnosed glucose type 2 diabetes. If ≥5.6 mmol/l, oral glucose tolerance test is strongly recommended but is not necessary to diagnose the syndrome

The proposed definition of the metabolic syndrome embraces overt diabetes and people with established cardiovascular disease, yet also purports to predict these as outcomes.² The “now you see it, now you don’t” approach to diabetes means that it can be included when estimating the apparent health consequences of the syndrome in population studies, yet becomes an end point in predictive analyses. From a more practical point of view, energetic screening and treatment for obesity, hypertension, and dyslipidaemia already form the basis of managing diabetes. Diagnosis of the metabolic syndrome adds nothing to the understanding or clinical management of people with known diabetes and is therefore redundant. Future consideration of the syndrome should exclude diabetes and known cardiovascular disease.⁵

Clinical value

The quest for a worldwide index of the health implications of central obesity is praiseworthy but problematic, given the limitations of waist circumference as a surrogate.³ Clinical measures do not need to be perfect, but they do need to be consistent, and the relation between girth and fat distribution varies from one population to another. Different waist measures are needed for different ethnic groups, and race―for which no satisfactory definition exists―thus enters the equation (table).⁴ Use of a sliding scale for waist circumference has the further consequence that an independent yardstick―cardiovascular risk―is then needed to calibrate one population with the next. The result is a circular definition, for vascular risk defines the syndrome and the syndrome defines vascular risk.

International Diabetes Federation definitions for central obesity

Country/ethnic group	Waist circumference (cm)
	Men	Women
Europid*	≥94	≥80
South Asians†	≥90	≥80
Chinese	≥90	≥80
Japanese‡	≥85	≥90
Ethnic South/Central Americans	Use S Asian values until more specific data are available
Sub-Saharan Africans	Use European data until more specific data are available
East Mediterranean/Middle East	Use European data until more specific data are available

*The US is likely to continue to use the adult treatment panel III values (102 cm men; 88 cm women) for clinical purposes.

†Based on a Chinese, Malay, and Asian-Indian population.

‡Subsequent data analyses suggest that south Asian values should be used for Japanese populations until more data are available.

Diagnosis of the metabolic syndrome enhances prediction of diabetes and cardiovascular disease, if these are not already present, but impaired glucose tolerance alone is better than the combined features of the syndrome in predicting diabetes,^{3 4 5} and it is unsurprising that combining known cardiovascular risk factors enhances cardiovascular risk. The metabolic syndrome is consistently outperformed by scoring systems that incorporate age, sex, and smoking together with personal and family history of heart disease. These have the further advantage of treating continuous variables as continuous, whereas the metabolic syndrome treats them as dichotomous.^{3 4 5}

In sum, the metabolic syndrome is a handy clinical label that lacks a useful definition. The latest attempt is characterised by an elastic measure of the proposed unifying feature―central obesity―and has no agreed pathophysiological basis. A flourishing academic industry has been founded on a diagnostic artefact with little prognostic or therapeutic value. Reaven himself bids farewell to his syndrome, in so far as clinical value is concerned, with the words requiescat in pace (rest in peace).³ To which we may add, Amen.