Should we dump the metabolic syndrome? No

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

The clustering of several disorders associated with increased risk of cardiovascular disease has been recognised for over 80 years,¹making claims that the drug industry invented the syndrome lack credibility. However, the modern concept of the metabolic syndrome started in 1988 with Reaven describing the clustering of insulin resistance, hyperinsulinaemia, glucose intolerance, hypertension, raised triglyceride concentration, and low high density lipoprotein cholesterol concentration.² Over the next decade other features, most notably central obesity, were found to be associated with this cluster. There was little argument about the existence of the clustering but confusion about its diagnosis. Different criteria abounded, the most widely used coming from the World Health Organization³ and the National Cholesterol Education Programme (adult treatment panel III).⁴ The International Diabetes Federation then brought the various groups together recommending a diagnostic set⁵ which was similar to the updated version of adult treatment panel III.⁶

Recognising that the syndrome provides a simple public health strategy to define those at higher risk, the federation’s definition provided a stepwise approach to risk with measurement of waist as a simple initial screening test followed by assessment of the other four components (hyperglycaemia, hypertension, raised triglyceride concentration, low high density lipoprotein cholesterol concentration). Several other factors are associated with this cluster but the federation felt that a practical set of measurements was needed that could be used in most primary care and hospital settings worldwide. Thus it did not include insulin resistance because it cannot easily be measured. The syndrome is becoming increasingly prevalent because of the current epidemic of obesity and sedentary lifestyle.^{7 8} It highlights the form of obesity that is associated with increased risk of diabetes and cardiovascular disease and pinpoints those at risk allowing targeted therapy.

Importance of a name

Recently the American Diabetes Association and the European Association for the Study of Diabetes questioned both the existence and usefulness of the metabolic syndrome.⁹ It was a comprehensive and thought provoking review which may have heightened interest in the syndrome but missed the point.

The review started by asking whether it was a syndrome at all. At its simplest syndrome means a collection of things. Our definition of metabolic syndrome is stronger: a cluster of inter-related risk factors for cardiovascular disease and diabetes with association greater than by chance alone. This has been shown repeatedly.^{10 11} Although the aetiology of the syndrome is uncertain, strong hypotheses implicate central adiposity, insulin resistance, and low grade inflammation.¹⁰ Aetiology is unknown for many other conditions whose existence is accepted, including type 2 diabetes. The syndrome is not attempting to create a new disease but to identify a risk state, like pre-diabetes (which was created by the American Diabetes Association) or dyslipidaemia.

Identifying risk

Although the syndrome has had several definitions during its evolution, today there are two main closely related definitions, as described above.^{5 6} Both use specific cut-off points for continuous variables, which allows them to be used in all clinical settings. The use of cut-off points is common throughout medicine where yes or no answers are the norm, including in the diagnosis of hypertension or diabetes. The decision to use different waist cut-off values for different ethnic groups is supported by available data that relate waist circumference to risk of diabetes and cardiovascular disease. For example, the prevalence of type 2 diabetes is consistently higher among Asians than Europids at any level of excess abdominal fat.^{4 12}

The syndrome is not intended to give an absolute risk of cardiovascular disease or diabetes but to highlight people at increased relative risk on whom doctors can then focus. Absolute risk would require information on other factors such as low density lipoprotein cholesterol concentration, family history, age, and smoking. The question also arises whether the risk associated with the syndrome is greater than the sum of the parts. The evidence is equivocal, but again it is irrelevant – risk increases with the number of abnormal components.

We believe the syndrome has clinical value. In the specialised academic world of the syndrome’s critics, every person may automatically have all known risk factors checked routinely but in the “real world” of primary health care, this definition helps identify people at high risk without the need for sophisticated technology. The federation’s recommendations provide a simple approach that will allow the identification of most people who are at risk. Other measurements can then be made and preventive steps taken to reduce the long term burden of disease. Although lifestyle measures are of prime importance, sometimes drug treatment is needed.

Focus on the syndrome has also brought diabetologists and cardiologists together, ensuring much better appreciation of risk of diabetes among cardiologists and cardiovascular disease among diabetologists. This results in better management of people with type 2 diabetes, given that over 70% of them may die from cardiovascular disease. The most important outcome is that clinicians are focused on high risk patients. The increased prevalence of the underlying causes of the metabolic syndrome (obesity and sedentary lifestyle) portends an enormous increase in cardiovascular disease and type 2 diabetes worldwide.⁴ The diagnosis of the metabolic syndrome provides a focus on the cluster of cardiovascular disease and diabetes risk factors that require attention and emphasises the multifactorial nature of the risk for these diseases. As such, the syndrome continues to have an important role in both public health and individual care.