Metabolic syndrome: the dysmetabolic state of dysfunctional adipose tissue and insulin resistance
Jean-Pierre Despre´s and H. Bryan Brewer
The current world epidemic of obesity represents atremendous medical and public health challenge. Amajor consequence of obesity has been a rapid accelera-tion in the prevalence of type 2 diabetes;
however, it isnow recognized that even before the development of dia-betes, many individuals have the constellation of athero-thrombotic inﬂammatory abnormalities characteristic of type 2 diabetes.
Thus, the cluster of metabolic abnorm-alities is not the consequence of the hyperglycaemicstate of type 2 diabetes but is rather pathophysiologicallyrelated to insulin resistance, the most prevalent form of insulin resistance being present in individuals with excessvisceral as well as ectopic fat.
Thus, even in the absenceof hyperglycaemia, abdominally obese patients with anexcess of visceral and ectopic fat deposition are likelyto have the clustering of risk factors associated withinsulin resistance. In this regard, the pivotal role of insulin resistance in the pathophysiology of the clusterof risk factors was ﬁrst reported by Reaven
and desig-nated syndrome X. Since his seminal paper, numerousgroups have utilized the term insulin resistance syndromein the description of this cluster of athero-thromboticinﬂammatory abnormalities.
In 2001, the guidelinesdeveloped by the National Cholesterol EducationProgram-Adult Treatment Panel III (NCEP-ATP III) commit-tee considered abdominal obesity as central in the patho-physiological development of the insulin resistancesyndrome.
Since the measurement of insulin resistancewas not practical in the context of primary care clinicalpractice, the guidelines provided clinicians with simplediagnostic criteria, including waist circumference, trigly-cerides, high-density lipoprotein (HDL) cholesterol, bloodglucose, and blood pressure to identify patients with thecluster of risk factors, resulting in an increased risk of diabetes and cardiovascular disease (CVD). The clusterof athero-thrombotic inﬂammatory risk factors wasdesignated as the metabolic syndrome. Many groupshave confused the NCEP-ATP III ﬁve criteria to diagnosethe metabolic syndrome in the context of clinical prac-tice with the conceptual deﬁnition of the syndrome.The deﬁnition of the metabolic syndrome has a pathophy-siological basis
and places insulin resistance andabdominal obesity at the core of the cluster of abnormal-ities. The NCEP-ATP III ﬁve criteria should not be con-sidered as the deﬁnition of the metabolic syndrome butrather as simple screening tools. Reﬁning the dis-criminating capabilities of these tools is work in progress.For instance, the International Diabetes Federation (IDF)
hasplacedmoreemphasisthanNCEP-ATPIIIontheimport-ance of abdominal obesity and recognized the importantethnic differences in susceptibility to visceral adiposityand related metabolic abnormalities.
Diagnosis of the metabolic syndromein clinical practice: does it matter?
Although many studies have shown that patients meetingthe NCEP-ATP III criteria for the metabolic syndrome areat increased risk of cardiovascular events,
the jointposition paper published by the American DiabetesAssociation-European Association for the Study of Dia-betes (ADA
has appropriately pointed out thata clinical diagnosis of the metabolic syndrome is notsufﬁcient to assess CVD risk and that attention shouldbe ﬁrst paid to classical risk factors such as age, malegender, blood pressure, smoking, low-density lipoprotein(LDL) cholesterol and HDL-cholesterol, and diabetes.These two organizations have even questioned the rel-evance of a clinical diagnosis of the metabolic syndromeand emphasized that attention should be ﬁrst given toassessment and management of classical risk factors.Therefore, although our toxic lifestyle characterizedby lack of physical activity and an energy-dense diethas led to an epidemic of abdominal obesity and of themetabolic syndrome,
whether its diagnosis in clinical
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European Heart Journal Supplements (2008)
(Supplement B), B1