Elsevier

The Lancet

Volume 365, Issue 9468, 16–22 April 2005, Pages 1415-1428
The Lancet

Seminar
The metabolic syndrome

https://doi.org/10.1016/S0140-6736(05)66378-7Get rights and content

Summary

The metabolic syndrome is a common metabolic disorder that results from the increasing prevalence of obesity. The disorder is defined in various ways, but in the near future a new definition(s) will be applicable worldwide. The pathophysiology seems to be largely attributable to insulin resistance with excessive flux of fatty acids implicated. A proinflammatory state probably contributes to the syndrome. The increased risk for type 2 diabetes and cardiovascular disease demands therapeutic attention for those at high risk. The fundamental approach is weight reduction and increased physical activity; however, drug treatment could be appropriate for diabetes and cardiovascular disease risk reduction.

Section snippets

Defining the metabolic syndrome

While the concept of the metabolic syndrome was accepted, and even while controversies have raged about its cause, it was not until 1998 that there was an initiative to develop an internationally recognised definition. In an attempt to achieve some agreement on definition, and to provide a tool for clinicians and researchers, a WHO consultation proposed a set of criteria.13 Subsequently, the National Cholesterol Education Program's Adult Treatment Panel III (NCEP: ATP III)14 and the European

Prevalence

Comparisons of published prevalence for different populations are difficult despite attempts to reach agreement on the definition of the metabolic syndrome.1 Many studies compare prevalences using different criteria, and perhaps their main achievement is to reinforce the need for a standardised international definition. Cameron and others1 have published a detailed review about the prevalence of the syndrome with different criteria (table 1).

Figure 1 presents studies from various countries.

Relation to predictability of diabetes and cardiovascular disease

The metabolic syndrome is associated with an increased risk of both diabetes5 and cardiovascular disease.9, 10, 28, 29 Several studies have indicated that the metabolic syndrome predicts future diabetes.30, 31 However, since impaired fasting glucose and impaired glucose tolerance are components of the NCEP:ATP-III and the WHO definitions respectively, this finding might not be a surprise.

In the DECODE study involving European men and women,32 non-diabetic people with the metabolic syndrome had

Insulin resistance

The most accepted and unifying hypothesis to describe the pathophysiology of the metabolic syndrome is insulin resistance. Insulin resistance has traditionally been defined with a glucocentric view—ie, when a defect in insulin action results in fasting hyperinsulinaemia to maintain euglycaemia. Yet, even before fasting hyperinsulinaemia develops, postprandial hyperinsulinaemia exists.

A major contributor to the development of insulin resistance is an overabundance of circulating fatty acids.

Beyond insulin resistance

Despite the substantial amount of evidence in support of the notion that the metabolic syndrome is an insulin resistance syndrome, quantification of insulin action in vivo is not always strongly related to the presence of the syndrome.111 Several key questions are raised. First, if the metabolic syndrome is a consequence of only insulin resistance, is the definition appropriately constructed? Second, is it possible that the current components and their relation to the metabolic syndrome exist

Management of metabolic syndrome

The presence of the metabolic syndrome carries increased risk for cardiovascular disease10, 118 and type 2 diabetes.117 Some affected people are at high or moderately high risk for major cardiovascular disease events in the short term (, ≤10 years); others are at less risk in the short term, but carry a fairly high long-term risk.119 In the latter group, therapeutic lifestyle modification is first-line therapy, but if 10-year risk is high, drug therapy to modify cardiovascular disease risk

Search strategy and selection criteria

We searched PubMed with the terms “metabolic syndrome”, “insulin resistance”, “coronary heart disease”, “diabetes mellitus”, “inflammation”, “hypertension”, “insulin secretion”, “CRP”, “cytokines”, and “adiponectin”.

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