Journal of Physiology and Pharmacology Advances

Metabolic Syndrome: Definition and Pathophysiology the

discussion goes on!
Thaman R. G. and Arora G. P.

J Phys Pharm Adv 2013, 3(3): 48-56

DOI: 10.5455/jppa.20130317071355

Online version is available on: www.grjournals.com

ISSN: 2251-7693

THAMAN AND ARORA

Review Article

Metabolic Syndrome: Definition and

Pathophysiology the discussion goes on!
1

Thaman R. G. and 2Arora G. P.

Sri Guru Ram Das Institute of Medical Sciences and Research, Amritsar, Punjab, India.
2
Deep Hospital, Ludhiana and Lundh University, Sweden

Abstract:
There are a number of official definitions of Metabolic Syndrome; still there is an ongoing international
debate on its existence. Metabolic syndrome is the result of highly complex interplay of a number of risk factors
and not a single etiology can be assigned to it. Genetic predisposition and environmental risk factors are
responsible for predisposition to the syndrome. The insight into the pathophysiology of metabolic syndrome
provide a practical tool to identify patients with an increased risk of cardiovascular disease (CVD) and diabetes
mellitus type 2. Increased prevalence of the syndrome affecting quarter of the world population, might be a
consequence of worldwide obesity epidemic, ageing population and increased insulin resistance.. Identification
of metabolic syndrome is a public health strategy to define susceptible people, which may prompt early
diagnosis of previously undetected components of metabolic syndrome. Simple life style modifications
specifically at the preliminary stage of the syndrome like weight reduction, regular exercise, diet modification,
decreasing the effect of insulin resistance by these modifications or drug treatment is promising in decreasing
the risk of CVD and type 2 diabetes. This reference article gives a balanced overview of the current knowledge
of the various definitions, pathophysiology, genetics and association between different risk factors. Keywords:
Pathophysiology, Cardiovascular disease (CVD), Type 2 Diabetes Mellitus, Risk factors, Genetics.

Keywords: Pathophysiology, Cardiovascular disease (CVD), Type 2 Diabetes Mellitus, Risk factors, Genetics

Corresponding author: Sri Guru Ram Das Institute of Medical Sciences and Research, Amritsar, Punjab, India. .
Received on: 11 Feb 2013
Revised on: 09 Mar 2013
Accepted on: 17 Mar 2013
Online Published on: 31 Mar 2013

48

J. Phys. Pharm. Adv., 2013, 3(3):48-56

METABOLIC SYNDROME: DEFINITION AND PATHOPHYSIOLOGY

Introduction and Definition

Metabolic syndrome is not a specific disease.
The metabolic syndrome is a constellation of
metabolic derangements such as insulin resistance,
hyperinsulinemia, abdominal obesity, impaired
glucose tolerance, dyslipidemia, hypertension, and a
proinflammatory and prothrombotic state (Reaven
GM, 1988). It is a common cause of the
development of atherosclerotic vascular disease and
type 2 diabetes (Haffner et al 1992, Isoma et al
2001). Here the association among the disorders
mentioned in the definitions of metabolic syndrome
is discussed in more detail and it is shown that their
clustering is not accidental in patients with insulin
resistance (Pacholczyk 2008). Metabolic syndrome
is also known as metabolic syndrome X,
cardiometabolic syndrome, syndrome X, insulin
resistance syndrome, Reaven's syndrome (named
for Gerald Reaven), and CHAOS (in Australia)
(Gale AE 1998). CHAOS stands for coronary artery
disease, hypertension, atherosclerosis, obesity and
stroke.
The modern concept of the metabolic syndrome
started in 1988 with Reaven. Reaven postulated that
insulin resistance (IR) was the cause of glucose
intolerance, hyperinsulinaemia, increased very-lowdensity lipoprotein (VLDL), decreased high-density
lipoprotein (HDL) and hypertension (Reaven GM,

1988). Twenty years later, the insulin resistance

syndrome has graduated to become the metabolic
syndrome .There was little argument about the
existence of the clustering of the diseases but
confusion about its diagnosis. Different criteria
abounded, the most widely used coming from the
World Health Organization (WHO 1999) and the
National Cholesterol Education Programme (adult
treatment panel III) (Executive Summary NCEP,
2001). The International Diabetes Federation then
brought the various groups together recommending
a diagnostic set which was similar to the updated
version of adult treatment panel III (Alberti et al
2009).
The National Cholesterol Education Program
Adult Treatment Panel III (NCEP ATP III) report
recommended the use of five variables for diagnosis
of the metabolic syndrome, including waist
circumference, serum triglyceride level, serum HDL
cholesterol level, blood pressure, and fasting
glucose level. Subjects meeting three of these five
criteria were classified as having the metabolic
syndrome (Executive summary NCEP, 2001).
Presently there is an ongoing debate regarding
the specific definition of MetS (Metabolic
Syndrome), but the most accepted group of factors
that are required to make the diagnosis are listed in
Table1.

Table 1: Diagnostic criteria and definition of metabolic syndrome.

Clinical Measure
WHO 1998
ATPIII 2004
Insulin Resistance
Impaired glucose tolerance (IGT), Impaired None
fasting glucose (IFG), Insulin resistance (IR) Any three of the
plus any two of the following;following five features;Dyslipidaemia
Triglycerides (TG)> 1.695mmol/L,
TG > 1.695mmol/L,
High density lipoprotein cholesterol (HDLHDL-C
C)
< 40mg/dL (males)
< 0.9mmol/L (males)
< 50mg/dL (females)
< 1.0mmol/L (females)
Blood pressure
> 140/90mmHg
> 130/85mmHg
Plasma glucose
> 7.0mmol/L (fasting)
>5.5mmol
Central obesity

Others

Waist/Hip ratio(WHR) > 0.90(males);

0.85(females) and or Body mass
index(BMI) > 30kg/m2
Urinary albumin excretion ratio > 20mg/min
or albumin/creatinine ratio > 30mg/g

Waist circumference >

102cm (males); > 88cm
(females)

IDF 2005
None
Any three of the
following five features;TG > 1.7mmol/L or on
TG Rx,
HDL-C < 1.03mmol or
on HDL-C Rx
> 130/85mmHg
> 5.5mmol/L ( includes
diabetes)
Waist circumference >
94 cm

World Health Organization, (1999), National Cholesterol Education Programme (adult treatment panel III) (2001), International
Diabetes Federation (2006).
49

J. Phys. Pharm. Adv., 2013, 3(3):48-56

THAMAN AND ARORA

Although the four definitions of Metabolic

Syndrome that were reviewed all recognize a
clinical entity with multiple risk factors for
cardiovascular disease, a careful examination
indicates many similarities and important
disparities. Resin and Alpert (2005) have proposed
a definition for Metabolic Syndrome that attempts
to bridge the differences among current definitions
and unify the risk factors. The Resin and Alpert
definition of Metabolic Syndrome is as follows:
Central obesity to be determined by ethnic cut-offpoints established by IDF, triglyceride > 150 mg/dl
or specific treatment, HDL cholesterol < 50 mg/dl
for women, < 40 mg/dl for men or specific
treatment, blood pressure >/= 130/85 mmHg or
specific treatment, fasting plasma glucose >/= 100
mg/dl and albuminuria mg/g albumin to creatinine
ratio >/= 30.
Prevalence
The increasing prevalence of the MetS,
associated with the substantial progression of
obesity and diabetes, makes it an important public
health concern (Levesque J, Lamarche B, 2008). On
the basis of this definition, the Third National
Health and Nutrition Examination Survey
(NHANES III) reported that the age-adjusted
prevalence of the metabolic syndrome in the U.S.
was 23.7%; the highest prevalence was found
among Mexican Americans (Ford ES 2002). In
Asia, use of the NCEP ATP III criteria is preferred
because they can be easily applied to the primary
care setting in many parts of Asia. Analyzing data
from the more recent NHANES 1999-2000 Ford,
Giles and Mokdad (2004) found that the prevalence
of Metabolic Syndrome has significantly increased
among U.S. adults older than 20 years, especially in
women. They also noted that the increase in the
prevalence of obesity between the NHANES III
1988-1994 and NHANES 1999-2000 was 22.9 to
30.5%, respectively. Their analysis showed that this
increase in obesity accounted for much of the
corresponding increase in Metabolic Syndrome.
Using the revised NCEP: ATPIII criteria, the
estimated prevalence of MetS increased up to 5%
during the last 15 years. The WHO criteria,
50

although more restrictive, estimated nearly the same

prevalence of MetS, whereas the IDF definition
which adopted a lower cut-off point for waist
circumference, estimated a higher prevalence (Kassi
E et al 2011).
Similarly to western societies, the prevalence of
MetS is rapidly increasing in developing countries.
The situation is similar in the Indian subcontinent
with the recent data suggesting that up to one fourth
and one third Indian adult population suffer from
metabolic syndrome (Misra A and Khurana L,
2008). This increase is observed regardless of the
criteria used and reflects the transition from a
traditional to a Western-like lifestyle. These
changes cause significant effects on body
composition and metabolism, often resulting in an
increase in BMI, generalized and abdominal
obesity, and an increase in dyslipidemia and type
2DM (type 2 Diabetes Mellitus) Intrauterine and
early postnatal undernutririon have been suggested
as one of the important causes of development of
metabolic syndrome (Misra A et al 2009). In
general, the International Diabetes Federation
estimates that one-quarter of the world's adult
population has Metabolic Syndrome (IDF 2006).
Second thoughts on validity of Metabolic
Syndrome
Recently the American Diabetes Association
and the European Association for the Study of
Diabetes questioned both the existence and
usefulness of the metabolic syndrome (Kahn R et al
2005). It was a comprehensive and thought
provoking review which may have heightened
interest in the syndrome but missed the point. The
syndrome is not trying to create a new disease but to
identify a risk state like pre-diabetes and
dyslipidemia (Alberti and Zimmet 2008). Although
the aetiology of the syndrome is uncertain, strong
hypotheses implicate central adiposity, insulin
resistance, and low grade inflammation (Grundy S
M et al 2005). The syndrome is not intended to give
an absolute risk of cardiovascular disease or
diabetes but to highlight people at increased relative
risk on whom doctors can then focus.
J. Phys. Pharm. Adv., 2013, 3(3):48-56

METABOLIC SYNDROME: DEFINITION AND PATHOPHYSIOLOGY

The number of people with the metabolic

syndrome is rising alongside obesity. Nevertheless,
Edwin Gale believes the diagnosis has little
practical value (Gale EAM, 2005). A cluster of
clinical features constitutes a syndrome, but
attempts to define the metabolic syndrome as a
clinical entity have been hampered by the lack of an
agreed unifying feature. Albert and Zimmet (2008)
believe it increases the detection of people at high
risk of diabetes and heart disease.
Another study by Pacholczyk M et al, 2008
discusses the association among the disorders
mentioned in the definitions of metabolic syndrome
in more detail and it is shown that their clustering is
not accidental in patients with insulin resistance.
There is lack of consensus about the definition of
metabolic syndrome as well its pathophysiology.
There is also lack of consensus on the criteria to be
used for the treatment of the syndrome and whether
treatment of the syndrome is different from
treatment of the components.
Pathophysiology of Metabolic Syndrome
Metabolic Syndrome is the consequence of
complex
interplay
between
genetic
and
environmental factors and hence the term Metabolic
Syndrome has become a hot topic of discussion in
medical literature. It is important to understand in
detail the pathophysiology of this syndrome in order
to identify people at risk of development of
cardiovascular disease. Identification of people at
risk will help in early intervention for prevention (
Lann D, LeRoith D 2007).
Insulin Resistance and Glucose Intolerance
Metabolic Syndrome is also known as Insulin
resistance syndrome. This syndrome is a cluster of
disorders like Insulin resistance, impaired glucose
intolerance and hyperinsulinemia. Insulin resistance
appears to be the primary mediator of metabolic
syndrome (Lann D, LeRoith D (2007). Insulin
promotes glucose uptake in muscle, fat, and liver
cells and can influence lipolysis and the production
of glucose by hepatocytes. The linked concepts of
metabolic syndrome/insulin resistance syndrome
have served a highly useful purpose by providing a
simple construct to characterize many types of
51

J. Phys. Pharm. Adv., 2013, 3(3):48-56

patients who clinicians see daily, and to help

identify people at risk (Yehuda H 2009).
Insulin is an antiatherogenic hormone and this
metabolic effect involves the activation of
phosphatidylinosital (PI) 3-kinase. In case of Insulin
resistance, PI 3- kinase path is impaired and Insulin
is no longer antiatherogenic (Wang et al 2004).
Obesity in particular abdominal adiposity is one of
the main reasons for Insulin resistance. Nonesterified fatty acids (NEFA) are released from
excess adipose tissues, which increase insulin
resistance. In case of Insulin resistance there is
increased lipolysis from the adipose tissue which
increases the free fatty acids, further inhibiting the
anti-lipolytic effect of Insulin. (Eckel et al 2005).
Visceral or omental fat appears to be the most
detrimental and contributes most to the
development of lipotoxicity in peripheral tissues by
the secretion of adipocytokines. (Gill et al 2005).
Metabolic Syndrome is associated with a high
amount of intra-abdominal fat, low adiponectin
levels, and elevated levels of cytokines (interleukin
1RA and interleukin 1beta). (Salmenniemi et al
2004). Hyperinsulinemia may increase the
production of very low-density lipoprotein
triglycerides and thus raise triglycerides. Insulin
resistance can raise blood pressure (Grundy, 2004).
Additional contributors to insulin resistance
include abnormalities in insulin secretion and
insulin receptor signaling, impaired glucose
disposal, and proinflammatory cytokines. The
relation of impaired glucose tolerance and Insulin
resistance is well documented. To compensate for
defects in insulin activity, insulin secretion or
clearance needs to be modified to sustain normal
glucose levels. Hyperglycemia is the end result if
these mechanisms fail (Eckel et al 2005). Since
insulin resistance increases a person's risk for
developing cardiovascular disease and Type 2
diabetes, several researchers have proposed
measures of insulin resistance in obese individuals
with and without Metabolic Syndrome. Reilly et al
(2004) believe that insulin assays or alternative
biomarkers of insulin resistance may facilitate
cardiovascular risk prediction in individuals with
Metabolic Syndrome.
Central Obesity

THAMAN AND ARORA

According to the new criteria of IDF,

Metabolic syndrome can also be called as central
obesity syndrome (Gary 2006). The importance of
the term Metabolic syndrome is that it helps identify
people at risk of Cardiovascular disease and Type 2
Diabetes (Ford 2005). Central obesity is a high
CVD risk factor. Central obesity is more
metabolically active then peripheral fat. Recently,
studies have suggested that central adiposity
precedes the development of the other components
of Metabolic Syndrome and that weight reduction at
that point could be the best way to prevent it.
Pladevall, et al., 2006, Steele, et al 2004,
recommends that waist circumference be routinely
measured to assess individuals for increased risk for
insulin resistance related cardiovascular disease,
Metabolic Syndrome and Type 2 diabetes and to
target
individuals
for
health
promotion
interventions. Though Insulin resistance is known to
be the major factor for the development of
metabolic syndrome, but it is suggested that obesity
provides the connection between the insulinresistant, dyslipidemic and hypertensive factors
(Wingard et al 1996).
Visceral fat releases their metabolic products
directly into portal circulation, which carries blood
straight to the liver. Therefore free fatty acids are
poured into the liver. Free fatty acids also
accumulate in the pancreas, heart and other organs.
This leads to organ dysfunction, producing impaired
regulation of insulin, blood sugar and cholesterol as
well as abnormal heart functions. This is known as
lipotoxicity (Havard College 2006).
We can evaluate abdominal obesity by using
computed tomography (CT) or magnetic resonance
imaging (MRI) to measure the amount of visceral
fat.
The National
Cholesterol
Education
Programme Adult Treatment Panel III suggested cut
off of 102 cm (40 in) and 88 cm (35 in) for males
and females as a marker of central obesity. Parikh et
al 2006 proposed that Index of central obesity,
which is the ratio of waist circumference and
height, was a better substitute than the widely used
waist circumference. Central obesity is correlated
with both insulin resistance and T2DM itself
(Gabriely et al 2002).
Hypertension
52

One of the key symptoms of metabolic

syndrome is hypertension. It is a silent symptom
which may remain undetected for long. It is an
important risk factor for development of
cardiovascular disease. All the hemodynamic and
metabolic disorders of essential hypertension and
insulin resistance are closely related. Essential
hypertension is frequently associated with several
metabolic abnormalities, of which obesity, glucose
intolerance, and dyslipidemia are the most common
( Ferranini et al 1991). Obesity may be the strongest
risk factor for uncontrolled hypertension. Studies
have shown that obesity provides a connection
between hypertension, insulin resistance and
dyslipidemia. (Wingard et al 1996). In another
study three factors were found in the clustering of
metabolic variables. These three factors were
insulin resistance, hypertension and dyslipidemia.
Both general and central obesity was associated
with insulin resistance and hypertension and only
weakly linked to dyslipidemia (Anderson PJ et al
2001). The results of Farmingham Heart Study
estimate the risk of excess weight was the cause of
hypertension in 78% of men and 65% of women
(Morse et al 2005).
Studies also suggest that both hyperglycemia
and insulin activate the RAS (Renin-Angiotensin
System) by increasing the expression of
angiotensinogen, AII, and the AT1 receptor, which,
in concert, may contribute to the development of
hypertension in patients with insulin resistance
(Malhotra et al 2001). There is cross talk between
the RAS and insulin signaling at multiple levels,
and the RAS appears to be important in
atherogenesis, Activation of RAS may inhibit the
action of Insulin via the PI3 pathway (Prasad et al
2001). There is also evidence which supports a
strong relation between hypertension and obesity,
which may involve insulin and leptin as well as
sympathetic nervous system. Leptin and insulin are
considered to be compensatory mechanisms
required to restore energy balance with sympathetic
nervous system as one of the effector arms
(Landsberg (2001).
Dyslipidemia
A study by Brown et al (2001) in the Kaiser
Permanente Northwest population, reported the
J. Phys. Pharm. Adv., 2013, 3(3):48-56

METABOLIC SYNDROME: DEFINITION AND PATHOPHYSIOLOGY

correlation between fasting lipids, HbA1c in 11938

persons with diabetes. The study compared persons
with no, one and two high-cardiovascular diseases
(CVD) risk lipid abnormalities, the HbA 1c was
7.3, 7.5 and 7.9%, triglycerides 150, 210 and 318
mg/dl and HDL 54, 40 and 37 mg/dl respectively.
This suggested a poorer glycemic control with
dyslipidemia in type 2 diabetes.
Another study by Lamarche et al (1997),
reported that the presence of small, dense LDL
particles may be associated with an increase of
subsequently developing Ischemic heart disease.
LDL particle size shows no correlation with the
LDL cholesterol, but it is strongly correlated with
triglyceride and HDL cholesterol concentrations
and with the cholesteroltoHDL cholesterol ratio.
In fact elevated triglycerides and low levels of HDL
cholesterol characterize dyslipidemia in Metabolic
Syndrome. In the presence of insulin resistance and
hyperinsulinemia, the circulating free fatty acids
result in the formation of triglycerides.
Sniderman et al (2003) in a symposium on
approaches to lipid-lowering treatment in persons
with diabetes presented the analysis of
hypertriglycerides and elevated apo B. It was
concluded that the true target in the treatment for
diabetes should be apo B rather than LDL
cholesterol. Without measurement of apoB
molecule,
one
cannot
distinguish
with
hypertriglyceridemia and large particles whose
apoB is normal.
ProInflammatory state
Yudgin et al (1999) noted that low-grade
inflammation is associated with insulin resistance
and endothelial dysfunction and that adipose tissue
generates inflammatory cytokines that may link
insulin resistance with vascular disease. The origin
of the inflammatory state and of endothelial
dysfunction was adipocyte-generated inflammatory
cytokines, which correlate strongly with insulin
resistance. Circulating signal molecules from fat
could include FFAs, adiponectin, IL-6 (particularly
at the liver, where IL-6 increases CRP production),
resistin, leptin, and TNF-. This study has sought
associations of levels of C-reactive protein and
interleukin-6 with measures of obesity and of
chronic infection as their putative determinants. The
53

J. Phys. Pharm. Adv., 2013, 3(3):48-56

study also related levels of C-reactive protein and

interleukin-6 to markers of the insulin resistance
syndrome and of endothelial dysfunction. Metabolic
syndrome and obesity are a kind of stress that leads
to activation of inflammatory pathways. The
causation of inflammation is multifactorial. The
inflammation in metabolic syndrome is not
accompanied by infection, autoimmunity or massive
tissue injury. In fact the inflammation is low grade
chronic inflammation. Researchers have attempted
to
name
this
inflammatory
state
as
metaflammation, meaning metabolically triggered
inflammation. A few studies have confirmed the
positive association between obesity indices and
inflammatory markers, mainly CRP (C - reactive
protein) in women (Shemesh 2007), but also other
inflammatory markers, both in women and men
(Mortensen 2009).
Increased concentrations of inflammatory
mediators, such as, C-reactive protein, tumor
necrosis factor-alpha, interleukin-6 and others have
been found in the obese. Adipose tissue has been
found to express most of these inflammatory
markers. Obesity was the most important feature
associated with C-reactive protein. (Dandona et al
2005).
Prothrombotic state
It is characterized by increased plasma
plasminogen activator inhibitor (PAI)-1 and
fibrinogen, also associates with the metabolic
syndrome. Fibrinogen, an acute-phase reactant like
CRP, rises in response to a high-cytokine state.
Thus, prothrombotic and proinflammatory states
may be metabolically interconnected. (Grundy et al
2004).
The study of plasminogen activator inhibitor-1
helps in better understanding of association between
hemostatic markers and metabolic syndrome. A
study was conducted by Aso et al (2005) to
determine whether plasma concentrations of
thrombin-activatable fibrinolysis inhibitor (TAFI) in
patients with type 2 diabetes were associated with
components of metabolic syndrome (MetS),
including high-sensitivity C-reactive protein (hsCRP), plasminogen activator inhibitor (PAI)-1, and
LDL cholesterol. The result indicated positive
correlation between LDL cholesterol and plasma

THAMAN AND ARORA

TAFI with type 2 diabetes mellitus. Co-existence of

metabolic syndrome and hypercholesterolemia
accelerates inflammation and elevated TAFI and
PAI-1, inhibits fibrinolysis. PAI-1 is an important
risk factor for metabolic syndrome. Three other
biomarkers, CRP, IL6, and fibrinogen associate also
importantly with the MetS cluster. These 4
biomarkers can contribute in the metabolic
syndrome risk assessment (Kraja AT et al 2007).
Genetics of Metabolic Syndrome
There is differing opinion on the definitions
and relatively low power of studies to detect the
subtle effects of genetic variation, therefore genetics
of metabolic syndrome is difficult to dissect. The
proposed candidate genes for metabolic syndrome
are involved in energy storage and often support the
thrifty phenotype (Speakman J R, 2006). When the
energy storing genetic variants are exposed to the
westernized environment and abundance of high
calorie food and physical inactivity, they may have
become detrimental and cause the phenotype with
metabolic disturbances observed in metabolic
syndrome, including obesity and glucose
intolerance. Clustering of genes in families suggest
a genetic component. Candidate genes have a
number of common variants which influence fat and
glucose
metabolism,
these
along
with
environmental factors can increase the susceptibility
to the syndrome. Among these, the genes for 3adrenergic receptor, hormone-sensitive lipase,
lipoprotein lipase, IRS-1, PC-1, skeletal muscle
glycogen synthase, etc. appear to increase the risk
of the metabolic syndrome. In addition, novel genes
may be identified by genome-wide searches.
Among genes contributing to the metabolic
syndrome, genes regulating lipolysis and
thermogenesis still remain prime candidates (Groop
L, 2000). To date, no unifying genetic factors
predisposing to metabolic syndrome have been
clearly identified. Several genes have however been
associated with at least two factors of metabolic
syndrome and are therefore considered to be most
promising candidate genes. The adrenergic breceptors ( ADRB1,ADRB2 AND ADRB3) have
been associated with obesity, hypertension and
glucose intolerance and can therefore be considered
54

as good candidates for predisposing to development

of Metabolic syndrome (Bengtsson, K. et al 2001,
Dionne, I.J. et al, 2002). Several potential candidate
genes have been suggested by their biologic
relevance, such as genes in systems of energy
balance, nutrient partitioning, lipid and insulin
metabolism,
lipolysis,
thermogenesis,
fuel
oxidation, and glucose uptake in skeletal muscle.
Many of these genes have been associated with
metabolic syndrome in various ethnic populations.
These candidate genes include but are not limited to
peroxisome proliferator-activated receptor (PPAR
), adiponectin, CD36, -adrenergic receptors,
insulin receptor substrates (IRS), 11 hydroxysteroid dehydrogenase type 1 (11-HSD1),
CRP, tumor necrosis factor- (TNF-), calpain-10
(CAPN10), upstream transcription factor 1, and
skeletal muscle glycogen synthase (Song Q, 2006).
An ongoing controversy still remains in genetic era,
as several genome wide linkage studies for
Metabolic syndrome or its components have been
performed yielding few chromosomal regions
displaying linkage to Metabolic syndrome or it
components, but no Metabolic syndrome
susceptibility genes as such in these regions have
yet been identified (Shmulewitz, D et al 2006,
Kraja, A.T. et al, 2005).
Conclusion
The insight into the pathophysiology of
metabolic syndrome provide a practical tool to
identify patients with an increased risk of
cardiovascular disease (CVD) and diabetes mellitus
type 2. Insulin resistance is one of the major risk
factors defining metabolic syndrome. It carries
increased risk of development of diabetes which
itself is a high risk condition for CVD. Different
criteria exist to define the syndrome. There is no
single widely accepted definition of metabolic
syndrome. The increasing awareness of the
pathophysiology, the risk factors and ways to
prevent them should be emphasized to formulate
treatment strategies for prevention of the disease.
Simple life style modifications specifically at the
preliminary stage of the syndrome like weight
reduction, regular exercise, diet modification,
decreasing the effect of insulin resistance by these
J. Phys. Pharm. Adv., 2013, 3(3):48-56

METABOLIC SYNDROME: DEFINITION AND PATHOPHYSIOLOGY

modifications or drug treatment is promising in

decreasing the risk of CVD and type 2 diabetes.
Future studies will provide researchers a better
understanding about the disease process and
treatment options. In depth study of the definition
and pathophysiology of metabolic syndrome is still
ongoing a study in progress.
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