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European Heart Journal Supplements (2008) 10 (Supplement B), B1–B3

doi:10.1093/eurheartj/sum051

Metabolic syndrome: the dysmetabolic state of


dysfunctional adipose tissue and insulin resistance
Jean-Pierre Després and H. Bryan Brewer

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The current world epidemic of obesity represents a designated as the metabolic syndrome. Many groups
tremendous medical and public health challenge. A have confused the NCEP-ATP III five criteria to diagnose
major consequence of obesity has been a rapid accelera- the metabolic syndrome in the context of clinical prac-
tion in the prevalence of type 2 diabetes;1 however, it is tice with the conceptual definition of the syndrome.
now recognized that even before the development of dia- The definition of the metabolic syndrome has a pathophy-
betes, many individuals have the constellation of athero- siological basis3,8 and places insulin resistance and
thrombotic inflammatory abnormalities characteristic of abdominal obesity at the core of the cluster of abnormal-
type 2 diabetes.2 Thus, the cluster of metabolic abnorm- ities. The NCEP-ATP III five criteria should not be con-
alities is not the consequence of the hyperglycaemic sidered as the definition of the metabolic syndrome but
state of type 2 diabetes but is rather pathophysiologically rather as simple screening tools. Refining the dis-
related to insulin resistance, the most prevalent form of criminating capabilities of these tools is work in progress.
insulin resistance being present in individuals with excess For instance, the International Diabetes Federation (IDF)9
visceral as well as ectopic fat.3 Thus, even in the absence has placed more emphasis than NCEP-ATP III on the import-
of hyperglycaemia, abdominally obese patients with an ance of abdominal obesity and recognized the important
excess of visceral and ectopic fat deposition are likely ethnic differences in susceptibility to visceral adiposity
to have the clustering of risk factors associated with and related metabolic abnormalities.
insulin resistance. In this regard, the pivotal role of
insulin resistance in the pathophysiology of the cluster
of risk factors was first reported by Reaven4 and desig- Diagnosis of the metabolic syndrome
nated syndrome X. Since his seminal paper, numerous in clinical practice: does it matter?
groups have utilized the term insulin resistance syndrome
in the description of this cluster of athero-thrombotic Although many studies have shown that patients meeting
inflammatory abnormalities.5,6 In 2001, the guidelines the NCEP-ATP III criteria for the metabolic syndrome are
developed by the National Cholesterol Education at increased risk of cardiovascular events,10,11 the joint
Program-Adult Treatment Panel III (NCEP-ATP III) commit- position paper published by the American Diabetes
tee considered abdominal obesity as central in the patho- Association-European Association for the Study of Dia-
physiological development of the insulin resistance betes (ADA–EASD)12 has appropriately pointed out that
syndrome.7 Since the measurement of insulin resistance a clinical diagnosis of the metabolic syndrome is not
was not practical in the context of primary care clinical sufficient to assess CVD risk and that attention should
practice, the guidelines provided clinicians with simple be first paid to classical risk factors such as age, male
diagnostic criteria, including waist circumference, trigly- gender, blood pressure, smoking, low-density lipoprotein
cerides, high-density lipoprotein (HDL) cholesterol, blood (LDL) cholesterol and HDL-cholesterol, and diabetes.
glucose, and blood pressure to identify patients with the These two organizations have even questioned the rel-
cluster of risk factors, resulting in an increased risk of evance of a clinical diagnosis of the metabolic syndrome
diabetes and cardiovascular disease (CVD). The cluster and emphasized that attention should be first given to
of athero-thrombotic inflammatory risk factors was assessment and management of classical risk factors.
Therefore, although our toxic lifestyle characterized
The opinions expressed in this article are not necessarily those of the
by lack of physical activity and an energy-dense diet
Editors of the Eurpean Heart Journal Supplement or of the European has led to an epidemic of abdominal obesity and of the
Society of Cardiology. metabolic syndrome,3 whether its diagnosis in clinical

& The European Society of Cardiology 2008. All rights reserved. For Permissions, please e-mail: journals.permissions@oxfordjournals.org
B2 Editorial

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Figure 1 The building blocks of global cardiometabolic risk. In this model, the metabolic syndrome as its most prevalent form (visceral obesity/ectopic
fat) is one more modifiable risk factor affecting global risk of cardiovascular disease. From Després and Lemieux.3

Figure 2 Assessment and management of global cardiometabolic risk. This illustration emphasizes the notion that in addition to assessing and managing
‘traditional’ risk factors, targeting excess visceral adiposity/ectopic fat could lower the risk of CVD through its effects on several determinants of
cardiometabolic risk.

practice would lead to different therapeutic manage- inflammation (e.g. C-reactive protein), insulin resistance
ment is a question frequently raised.13 To address this (insulin), an atherogenic dyslipidaemia (apolipoprotein B
issue, additional prospective data with hard CVD end and LDL particle size), and possibly select cytokines
points and a comprehensive set of morphometric and derived from adipose tissue (e.g. adiponectin and
metabolic markers are needed to sort the key predictors interleukin-6) may be useful in risk assessment but their
of risk beyond what is currently assessed by physicians. added value in global risk assessment, is frequently
At present, there is evidence14–17 that markers of debated due to the lack of adequate data. Furthermore,
Editorial B3

there are no data available on whether visceral adiposity Cardiometabolic Risk which is supported by an unrestricted
and ectopic fat predict CVD beyond or independently grant from Sanofi-Aventis awarded to Université Laval.
from classical CVD risk factors. Studies are underway to
address these issues. Conflict of interest: none declared.
An additional limitation that has not been adequately
addressed with our current approach to diagnose the
metabolic syndrome is that it is an all or none diagnosis
(present vs. absent) rather than containing graded com-
ponents assessing severity. In addition, because of this References
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Dr. Després is the Scientific Director whereas Dr. Brewer is a risk factors in overweight patients with dyslipidemia. N Engl J Med
member of the Executive Board of the International Chair on 2005;353:2121–2134.

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