Definitions and mechanisms of the metabolic syndrome

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Purpose of review

The phenomenon of risk factor clustering is called ‘metabolic syndrome’. The metabolic syndrome is the subject of great current interest and controversy.

Recent findings

The metabolic syndrome is an aggregation of risk factors for cardiovascular disease and type 2 diabetes. Risk factor clustering does occur but its specific cause(s) remains incompletely known. Insulin resistance and obesity are often involved. Five current definitions of metabolic syndrome exist, but they do not identify equivalent phenotypes. ATP3 metabolic syndrome, the most widely promoted definition, defines a lipid-centric phenotype but is a much stronger predictor of diabetes than of cardiovascular disease. ATP3 metabolic syndrome is not uniformly associated with insulin resistance, and in the absence of insulin resistance may not be a disease risk factor. The value of metabolic syndrome beyond more sophisticated prediction rules to discriminate future diabetes or cardiovascular disease risk is unclear. Abnormal adipocyte signaling, inflammation, or endothelial dysfunction may underlie risk factor clustering, but this is also an area needing more research.


Risk factor clustering occurs and is partly driven by obesity. It is critical to question current constructs of the metabolic syndrome in order to define more clearly the underlying causes of risk factor clustering.

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