Metabolic syndrome: To be or not to be?

The metabolic syndrome (MetS), a constellation of cardiovascular risk factors, has become one of the major public-health challenges worldwide (1). The MetS was first described by Kylin in the 1920s as the clustering of hypertension, hyperglycaemia and gout (2). Gerald Reaven was the first investigator establishing the significance of this syndrome (‘Syndrome X’) in his Banting lecture in 1988 (3). According to Reaven the primary value of his syndrome (also called ‘the insulin resistance syndrome’) was to provide a conceptual framework with which to place apparently unrelated biological events into a pathophysiological construct. About 10 years later the concept took another turn when the MetS was introduced as a diagnostic category by the definitions of the World Health Organization (WHO), the European Group for the Study of Insulin Resistance (EGIR), and the National Cholesterol Education Program – Third Adult Treatment Panel (NCEP ATP III) (4–6). Recently the International Diabetes Federation (IDF) presented new criteria for the MetS (7), and also the NCEP ATP III updated its definition (8). The starting point for the IDF definition was a need for one simple definition/diagnostic tool for clinical practice which could be used in any country by any physician to identify patients at considerably increased risk of developing cardiovascular disease and/or type 2 diabetes. All definitions of the MetS include the following components: obesity, insulin resistance or raised blood glucose, dyslipidaemia and elevated blood pressure. According to the WHO and EGIR criteria, insulin resistance was thought to be the driving force for the syndrome, whereas NCEP ATPIII introduced the significance of central obesity (large waist circumference) for cardiovascular risk factor clustering. According to the new IDF definition of the MetS, central obesity is a prerequisite for the syndrome (7). The rationale for this requirement is that central obesity is more strongly associated with the other MetS features than is any other parameter (9). Furthermore, central obesity is highly correlated with insulin resistance. Recommended cut-off points for waist circumference vary for different ethnic groups. In contrast, when the American Heart Association recently updated the NCEP ATP III criteria, no single risk factor was a requirement for the clinical diagnosis of this syndrome (8). There is no evidence or consensus on what is the predominant underlying cause (or causes) of the MetS. Insulin resistance and abdominal obesity have been assumed to be underlying causes for this syndrome, but there are no convincing data to show which one of these two (or neither) is the primary abnormality. Insulin resistance is present in the majority of subjects with the MetS, and it strongly associates with a number of other components, although the association with hypertension is weak. Therefore, the selection of abdominal obesity as a primary candidate for the MetS in the IDF definition is based more on clinical utility than on research evidence. Although none of the definitions of the MetS includes markers of thrombosis or inflammation, it is generally believed that the prothrombotic and proinflammatory state are characteristic features of the MetS (8). About the same time as the IDF presented a new definition of the MetS this year, the American Diabetes Association and the European Association