‫بسم هللا الرحمن الرحيم‬
Metabolic syndrome
By
Dr Amr Abdelmonem,MD.
Assistant professor of cardiothoracic anesthesia ,surgical
intensive care and clinical nutrition in faculty of medicine,
Cairo university
Member of North American Association For The Study Of
Obesity
What is metabolic syndrome?
• Metabolic syndrome is a collection of
health risks that increase the chance
of developing heart disease, stroke,
and diabetes.
• The condition is also known by
other names including Syndrome X,
insulin resistance syndrome, and
dysmetabolic syndrome.
What are these health risks?
ATP III Guidelines
WHO Guidelines
Abdominal Obesity
Waist Circumference
Men > 40 inches (102 CM)
Women > 35 inches (88 CM)
Other Variables
Triglycerides 150 mg/dL
HDL-Cholesterol
Men < 40 mg/dL
Women < 50 mg/dL
Blood Pressure 130/ 85 mm Hg
Fasting Glucose 110 mg/dL
Waist/Hip Ratio
>0.90
>0.85
 150 mg/dL
<35 mg/dL
<39 mg/dL
>140/>90 mm Hg
110 mg/dL
WHO guidelines also include microalbuminuria (>20 µg/min or albumin:creatinine ratio
>30 mg/g).
The Pathogenesis of metabolic syndrome
Environmental lifestyle-related factors:
When we eat ,our bodies break down the food
into its basic components ( proteincarbohydrates- fat), and absorbs them into
blood stream  rise in blood sugar 
pancreas will release insulin moves sugar
into cells either burned for energy or stored
away as fat in fat cells or glycogen in liver
and muscles
Years of dietery abuse in susceptible patients
 malfunctioning of insulin sensors 
hyperinsulinemia
Continued dietery abuse  insulin sensors
to sluggish  insulin resistance
Markers of insulin resistance :
Hypertriglyceridemia
HDL
Hypertension
Hyperinsulinemia (>15µu/ml) Marc C,et al. Obes
Res.2005;13:703
Abdominal obesity
Hyperglycemia
Marjo etal , proven liver fat accumulation as an
important marker Obes Res 2002; 10: 859
It is now clear that an individual could be
insulin-resistant from one of two main reasons
1. he/she could be genetically
resistant (like Reaven’s group) or
2. Could acquire the resistance by
becoming obese
Obesity
Lets walk through the fat metabolism pathway and
follow the flow of fat molecules:
Fat travels in the form of triglycerides  at cells 
ezymatic breakdowen  fatty acids enter the cells
mitochondria  breakdowen fat  in order to
enter mitochondria ,fats need carnitine 
insulin inhibits Fat- carnitine shuttle system 
fats move back into blood
Glucagon
accelerates this shuttle system
Muscle ,liver, kidney, lung, heart and other cells
break down fat
Fat cells merely store the fat molecules !
Two enzyme systems on the surface of fat cells
regulated by insulin and glucagon
Insulin stimulates lipoprotein lipase that transports
fatty acid into fat cells
Glucagon stimulates hormone sensitive lipase
that releases the fat from fat cells into the blood
Although we cannot control lipoprotein lipase
directly, we can control It indirectly by cotrolling
the metabolic hormones ,insulin and glucagon
DYSLIPIDEMIA
Where does cholesterol come from?
80 % comes from the body itself , every cell in the
body is capable of making its own cholesterol ,
most don’t and rely instead on that made in the
liver and skin.
Cholesterol and triglycerides are insoluble in blood
Lipoproteins are envelops that enclose cholesterol
and triglycerides Making them soluble in blood,so
that they can be transported to tissues
Sequence of events in the life of lipoproteins
Liver
Makes and release VLDL
HDL
Released to tissues
Deposited in coronary
arteries
TRIGLYCERIDES
WITH CHOLESTEROL
Removed by liver
CholesteroL
rich
VLDL
TRI AND CHOLES
LDL
More triglycerides release
Scavenges cholesterl
From tissues carries
Through blood
Hands it off to
Cholesterol
Bulk +tri
LDL
MATURE
VLDL
Triglycerides
Released to blood
And tissues
When the level of cholesterol inside the cells falls 
LDL receptors Attach to the surfaces of the hepatic
cells invaginate LDL cholesterol By endocytosis
Obese patients with insulin resistance have LDL
receptors dysfunction
Cholesterol synthesis inside the cells depends on
an enzyme named
3- hydroxy-3 methyl-glutaryl-coenzyme A reductase
Couple of hormones affect the activity of the rate
limiting enzymeHMG-CoA reductase
INSULIN AND GLUCAGON
Hypertension
Data from NHANES III show that the
(age – adjusted prevalence)
Of high blood pressure increases progressively
with higher levels Of BMI in men and women
High blood pressure is defined as
SBP 140 mm Hg
or MBP  90 mm Hg
or currently taking antihypertensives
What is the etiology that connects
obesity and hypertension?
Hyperinsulinemia and Insulin resistance
Mechanism
1. Increased sodium retention
2. Increased sympathetic nervous system
activity
3. Alteration in the mechanics of blood
vessels
Recently
Type II Diabetes mellitus
•The cells become resistant to insulin that even
large amounts cant adequately move the sugar into
cells
•Resistin is a protein secreted by fat cells as a
signal from adipose tissue linking obesity to insulin
resistance and type II diabetes
Liese et al, Eur J Nutr.2001;40:282
•Increased White blood cell count is correlated with
insulin resistance in diabetic obese females
Pannacciulli et al,Obes Res.2003;11:1232
Coronary artery disease
• Observational studies have shown that
overweight,obesity, and VAT are directly related to
cardiovascular risk factors
(  cholesterol ,  LDL,  triglycerides, hypertension, 
fibrinogen,hyperinsulinemia ,  HDL, plasminogen
activator inhibitor )
The term "Syndrome X" refers to a heart condition where
chest pain and electrocardiographic changes that suggest
ischemic heart disease are present, but where there are no
angiographic findings of coronary disease.
RECENTLY
Complement 3 and acute phase proteins is the
immunological link between central obesity and CHD
Obesity and cardiac dysrhythmias
(prolonged Q-T interval)
• Q-T interval is usually measured in lead II , and is
corrected for heart rate .
• Q-Tc= measured Q-T  square root of R-R interval
• Prolonged Q-T interval reflects prolonged
repolarization of the ventricle
• Proposed mechanism is increased SNS activity
• Recent study had found that Prolonged Q-T
interval is associated with abnormal WHR ,higher
levels of FFA and hyperinsulinemia in obese
women .
• Wight loss leads to normalization of Q-Tc with
attenuation of hyperinsulinemia
Esposito et al,Obes Res.2003;11:653-659
Oxidant Stress
Imbalance
Between
Formation
Of
Reactive oxygen/nitrogen species
(ROS/RNS)
And
Antioxidants
Pathologic stress 
(TNF
Induces monocytes to release mediators
and interleukins 1-6-8) 
Activates PMNs 
Release ROS(superoxide (O2·-), hydrogen
peroxide, hypochlorite, nitric oxide (NO),
hydroxyl radical 
Induce tissue injury by:
1.
2.
3.
•
•
damaging DNA
Cross linking cellular proteins
Peroxidation of membrane lipids 
Diminishing membrane fluidity
Increasing membrane permeability
Oxidant Stress and Obesity
•Adipocytes and preadipocytes have been
identified as sources of inflammatory
cytokines:
including TNF , interleukin (IL)1-ß, and IL-6.
•Stimuli capable of inducing cytokine
release from adipocytes may include:
lipopolysaccharides, intracellular triglycerides, and
catecholamines
We could predict that:
•The accumulation of intracellular triglycerides or
tissue adiposity promotes increased oxidant stress
•Therefore reduction of total body fat through diet
and/or exercise may be an effective means of
reducing systemic inflammation and oxidant stress.
Consistent with this prediction
Reductions in plasma markers of oxidant stress and
in ROS generation by isolated leukocytes have
been observed after 4 weeks of energy
restriction and weight loss.
Dandona et al. J Clin Endocrinol Metab,2001; 86:355-363
Good news
Physical activity 
•Decreases adipose derived inflammatory
mediators
•Activates signaling pathways that lead to
increased synthesis of intracellular antioxidants and
antioxidant enzymes and decreased ROS production
Miyazaki et al, Eur Appl Physiol.2001; 84:1-6
Pischon et al, Obes Res.2003;11:1055
A novel pathway to the manifestations of
metabolic syndrome(2004)