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Abstract
The metabolic syndrome is a cluster of metabolic abnormalities associated with increased
risk for cardiovascular disease and type 2
diabetes. The most commonly used criteria to
define the metabolic syndrome include the presence of abdominal obesity, high blood pressure,
elevated fasting plasma glucose and dyslipidemia
(high triglyceride and/or decreased HDL cholesterol). There is great variation in the prevalence
of the metabolic syndrome worldwide, with
increasing trends related to the epidemic of obesity in most countries. Insulin resistance and a
state of chronic inflammation are also underlying
factors contributing to this syndrome. C-reactive
protein is an emerging biomarker that may be
useful for risk stratification. The presence of the
metabolic syndrome identifies those with higher
long-term cardiovascular risk and thus calls for
intensified lifestyle therapy weight loss,
increased physical activity and antiatherogenic
diet. In some patients, pharmacologic interventions may be indicated for the management of
specific components of this syndrome, mostly
depending upon the severity of the abnormality.
Further studies are needed to define treatment
algorithms for patients diagnosed with the metabolic syndrome based on a particular combination of its components.
Key words:
Metabolic syndrome, cardiovascular disease, diabetes,
insulin resistance, obesity, inflammation, mortality
Diagnostic criteria
The most commonly used diagnostic criteria
have been those of the WHO definition [10] and
the NCEP/ATP III definition [11], which was
updated in 2005 [13]. Recently the International
Diabetes Federation (IDF) published its definition of the metabolic syndrome (Table I) [14].
The latter two definitions are the more easily
applicable tools to assess the metabolic syndrome
in clinical practice.
It has been speculated that the predictive value
of the NCEP and WHO definitions may depend
on the prevalence of the core metabolic components (dyslipidemia, hypertension, obesity and
glycemia) in the population under investigation
[15]. Thus the usefulness of the NCEP vs. WHO
criteria with a differing emphasis on the components of the metabolic syndrome may vary
according to the background population to
which they are being applied. Prevalence estimates for the NCEP/ATP III definition of the
International Diabetes Monitor
Review articles
Table I: Criteria for clinical diagnosis of the metabolic syndrome.
Clinical measurea
Abdominal obesity
140/90 mmHg
or specific medication
Elevated triglyceride
<35 mg/dl (0.9 mmol/l) (M) <40 mg/dl (1.03 mmol/l) (M)
<39 mg/dl (1.0 mmol/l) (F) <50 mg/dl (1.29 mmol/l) (F)
or specific medication
(M)
WHR, Waist-hip ratio; M, male; F, female; IGT, impaired glucose tolerance; IFG, impaired fasting glucose; T2DM, type 2 diabetes.
a
3 of 5 constitute diagnosis of the metabolic syndrome.
b
WHO definition: hyperglycemia (type 2 diabetes, IGT, IFG) or insulin resistance plus two other criteria (obesity, dyslipidemia, hypertension, microalbuminuria [albumin excretion 20 g/min or albumin:creatinine ratio 30 mg/g]).
c
IDF definition: abdominal obesity (ethnicity specific) plus two other criteria.
d
Top quartile of fasting insulin in non-diabetic population.
metabolic syndrome have been reported for several countries (Fig. 1) [1631]. These differ with
respect to the sample selection, the year in which
they were conducted, the precise definition used,
and the age and sex structure of the population.
There is a wide variation of prevalence by gender
and race/ethnicity [22].
Two more criteria sets for the diagnosis of the
metabolic syndrome have been suggested by the
American Association of Clinical Endocrinologists [32] and by the European Group for the
Study of Insulin Resistance [33]. The key differences from the NCEP and IDF criteria are that
both of these criteria sets are totally founded
on insulin resistance and exclude patients
with diabetes.
The IDF clinical definition requires abdominal obesity for metabolic syndrome diagnosis, as
a good surrogate for the more cumbersome measurement of insulin resistance and to reduce the
amount of laboratory testing necessary for identification. When abdominal obesity is present,
two additional factors originally listed in the
NCEP definition and now somewhat modified
are sufficient for diagnosis. The IDF emphasized
the presence of ethnic and national differences in
the abdominal obesity threshold [14, 34]. Recent
analyses in the US population (19992002)
showed that the IDF definition leads to a higher
prevalence estimate of the metabolic syndrome
(39%) than that based on the updated NCEP
definition (34.5%) [25], particularly in Mexican
American men.
2
Review articles
Mexico (19971999)
Saudi Arabia (19952000)
Women
Men
Iran (19992001)
Turkey (2000)
USA (19992002)
Venezuela (19992001)
Portugal (2000)
USA (19881994)
Oman (2001)
Greece (2003)
Spain (20002003)
Italy (2000)
South Korea (1998)
India (2003)
Australia (19992000)
France (1996)
0
10
20
30
40
50
60
Prevalence (%)
Fig. 1: Prevalence of the metabolic syndrome in several countries according to NCEP/ATP III criteria. Data from a recent analysis
of a national survey showed a prevalence of 34% in Mexico (personal communication from Simon Barquera, MD, PhD).
drome: the effects of mild to moderate hyperglycemia, the effects of compensatory hyperinsulinemia, and the effects of unbalanced pathways
of insulin action. In insulin resistance conditions, the ability of insulin to augment glucose
uptake and inhibit hepatic glucose production is
impaired. The resultant hyperglycemia presents
a stimulus to the -cells, which secrete large
amounts of insulin after meals. In individuals
in whom -cell dysfunction occurs, glucose
intolerance and type 2 diabetes may develop,
and the development of hyperglycemia is associated with an increasing prevalence of the metabolic syndrome.
The two major pathways for insulin signaling
are the phosphatidylinositol 3-kinase (PI3K) and
the mitogen-activated protein (MAP) kinase
pathways [42]. In the metabolic syndrome the
pathways leading to activation of PI3K are
impaired, whereas the MAP kinase pathway,
which mediates the mitogenic and proinflammatory responses of insulin signaling, may be overstimulated [43], leading to unbalanced combinations of both reduced as well as excessive
Volume 18, Number 5, 2006
Obesity
During the last decade, newly discovered adipokinetic pathways have suggested novel pathophysiologic mechanisms linking increased adipose tissue mass with the development of insulin
resistance and other components of the metabolic syndrome [44]. In the Insulin Resistance
Atherosclerosis Study [45], the strongest predictor of the metabolic syndrome was waist circumference; thus, abdominal obesity may precede
International Diabetes Monitor
Review articles
Underlying
factors
Metabolic
factors
Insulin
resistance
Dyslipidemia
Hypertriglyceridemia
Small, dense LDL
Inflammation
Abdominal
obesity
Clinical
outcomes
Cardiovascular
disease
Low HDL
Hypertension
Type 2
diabetes
Hyperglycemia
Hypercoagulability
Review articles
roles in the pathogenesis of CVD and type 2 diabetes [68]. The levels of C-reactive protein and
IL-6 increase with the degree of adiposity and
may lead to higher insulin resistance and the risk
of developing type 2 diabetes [69]. To the extent
that elevated IL-6 and C-reactive protein levels
reflect adipocyte activation, the availability of
these markers represents an approach for early
identification of individuals at increased risk
of the metabolic syndrome, type 2 diabetes
and CVD.
Review articles
In a recent review of prospective studies using
the NCEP and WHO definitions of the metabolic syndrome, Ford [73] found that the PAR
for type 2 diabetes was between 30% and 52%.
Acknowledgments
Dr Florezs work is supported by grants from the
Department of Veterans Affairs MiamiGRECC
and CSP#465, Pan American Health Organization RC/RG-T/VEN/3201, and UMHumana
Health Service Research. Dr Goldbergs work is
supported by grants from the National Institutes
of Health NIDDK DK01 0500 and
2RO1HL36588-16.
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