Aggregation of risk factors: the metabolic syndrome

The metabolic syndrome refers to an aggregation of atherogenic risk factors including dyslipidemia, hypertension, hyperglycemia and the presence of prothrombotic and inflammatory risk markers. The syndrome may represent the metabolic complications of abdominal obesity, with insulin resistance playing a major role. Individuals with the metabolic syndrome are at increased risk for type 2 diabetes mellitus. It has been suggested that the CHD risk of persons with the metabolic syndrome should be regarded as being greater than that calculated purely on the basis of, for example, the PROCAM score. Unfortunately, three sets of criteria for diagnosing the metabolic syndrome are in common use (WHO 1999 [insulin resistance], ATP III 2003 [environment], IDF 2005 [obesity]). These were proposed by the Third Adult Treatment Panel of the U.S. National Cholesterol Education Program (NCEP ATP), the World Health Organization (WHO) and the International Diabetes Federation (IDF). While showing a large degree of overlap, these criteria differ in the following important respects:

The NCEP ATP criteria emphasize environmental causes and suggest that abdominal obesity is a consequence of an energy-rich diet and a sedentary lifestyle. Recently, these criteria suggested lowering the threshold for normal fasting plasma glucose to 100 mg/dL (5.5 mmol/L). These criteria are widely used in the U.S. and Europe.

The WHO criteria emphasize the presence of insulin resistance and, in some subjects, require the measurement of fasting plasma insulin and formal assessment of insulin resistance using the homeostasis model assessment (HOMA) index. For these reasons these criteria are less frequently used in clinical practice.

The IDF emphasizes the presence of an elevated waist circumference as a mandatory clinical criterion of the metabolic syndrome. Population-specific waist circumference cutoffs to define abdominal obesity were proposed, although these have not been validated against clinical endpoints.

Recently, there has been much discussion on the usefulness of the metabolic syndrome as a nosologic entity, with some claiming that “diagnosis of the metabolic syndrome is redundant in those who already have diabetes and adds nothing to the management of those who do not¹. However, the term is still in common usage and is therefore discussed here at some length.

1. Gale, A.M., Albertik, K.G.M.M., Zimmet, P.Z. Should we dump the metabolic syndrome? Br Med J 2008; 336: 640-641.