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METABOLIC SYNDROME
DrVinoth Gnana Chellaiyan D

International Diabetes Federation Definition:
Abdominal obesity plus two other components: elevated BP, low
HDL, elevated TG, or impaired fasting glucose

Definition
Constellation of metabolic
abnormalities that confer increased
risk of cardiovascular disease(CVD) and
diabetes mellitus.

Alternative names
? Metabolic syndrome
? Syndrome X
? Insulin resistance syndrome
? Deadly quartet
? Reaven’s syndrome

The major features of metabolic syndrome include
?Central obesity
?Hypertrilgyceridemia
?Low high density lipoprotein (HDL)
?Hyperglycemia
?hypertension

EPIDEMIOLOGY
? Prevalence increases with age
? Greater industrialization and urbanization
? Increase in waist circumference is found predominantly
in women.
? Fasting TG>150 mg/dl and hypertension more likely in
men.

Risk factors
? Overweight/ obesity- central (key feature)
? Sedentary lifestyle
? Predictor of CVd events and associted mortality
? Associated with central obesity, TG’s, HDL, BP, glucose intolerance
? Aging- prevalence increases with age
? Diabetes mellitus- approx. 75% of T2DM or IGT have metabolic syndrome
? Coronary heart disease- 50% of CHD patients have metabolic syndrome
?
? About 1/3rd of
MS patients have premature CAD
? Lipodystrophy- both genetic or acquired have severe insulin resistance

CLINICAL FEATURES
? Usually asymptomatic and a high index of suspicion
is needed for diagnosis
? Examination -
?Increased waist circumference
?Increased Blood Pressure
?Lipoatrophy
?Acanthosis nigricans/ skin tags
Should alert to
search for other
abnormalities

metabolic syndrome and its clinical implications

Other associated
conditions
1) Cardiovascular disease
increased risk for new onset CVD, ischemic stroke, PVD
2) Type 2 diabetes mellitus
increased risk by 3-5 folds
3) NAFLD and/or NASH
4) Hyperuricemia
5) PCOS- prevalence 40-50%
6) OSA- commonly associated with obesity, HTN & insulin
resistance (CPAP improves insulin sensitivity)

IDF criteria
1. Waist circumference: ≥90 in males ≥80 in females
2. Plus two or more of the following
a) Hypertriglyceridemia: ≥150 TG’s or specific medication
b) Low HDL cholesterol: <40(M) and <50(F) or specific
medication
c) Hypertension: blood pressure ≥130 mm systolic or ≥85 mm
diastolic or specific medication
d) Fasting plasma glucose: ≥100 mg/dl or specific medication
or previously diagnosed T2DM

IDF criteria
*Diagnosis is established when ?3 of these risk factors are present.
?
Abdominal obesity is more highly correlated with metabolic risk factors than is
?
BMI. ?
Some men develop metabolic risk factors when circumference is only
marginally increased.
<40 mg/dL
<50 mg/dL or Rx for ↓ HDL
Men
Women
>90 cm
>80 cm
Men
Women
?100 mg/dL or Rx for ↑ glucose
Fasting glucose
?130/?85 mm Hg or on HTN Rx
Blood pressure
HDL-C
?150 mg/dL or Rx for ↑ TG
TG
Abdominal obesity?
(Waist circumference?
)
Defining Level
Risk Factor

Waist circumference Country / Ethnic group
94
cm
80
cm
Male
Female
Europids
*
In the USA, the ATP III values ( 102 cm male; 88
cm female) are likely to continue to be used for
clinical purposes
90
cm
80
cm
Male
Female
South Asians
Based on a Chinese , Malay and Asian-Indian
population
90
cm
80
cm
Male
Female
Chinese
90
cm
80
cm
Male
Female
Japanese
**
Use South Asian recommendations until
more specific data are available
Ethnic South and Central Americans
Use European data until more specific
data are available
Sub-Saharan Africans
Use South Asian recommendations
until more specific data are available
EMME ( Arab) populations
IDF criteria contd…

Pathogenesis
? Insulin resistance
? Increased waist circumference
? Dyslipidemia
? Glucose intolerance
? Hypertension
? Decreased adiponectin levels

Pathogenesis contd…
? Central obesity is the keystone for pathogenesis of
“METABOLIC SYNDROME”
? Central obesity leads to insulin resistance.
? Various factors that play a role in pathogenesis includes:
?IL-1, IL-6, IL-18
?Resistin
?TNF-alpha
?CRP
? Adiponectin an anti inflammatory cytokine is reduced
in metabolic syndrome.

Pathogenesis contd…
Impaired insulin
mediated glucose
uptake
Toxic injury to
pancreatic islets
Increased insulin
resistance
Hyperglycemia Type 2 DM
Insulin resistance pp/fasting hyperinsulinemia
Lipolysis by LPL Abundance of FFA’s

How to diagnose?
? IDF criteria
? H/o symptoms of OSA in all patients
? H/o PCOS in premenopausal women
? Family H/o CVD and DM
? Waist circumference and BP measurement
? Laboratory investigations
? Fasting lipid profile and fasting glucose
? hs-CRP, fibrinogen, uric acid, urinary microalbumin
? LFT for NAFLD
? Sleep study for OSA
? Testosterone, FSH, LH for PCOS

? Weight reduction- include a combination of caloric restriction,
increased physical activity, and behavior modification.
LIFESTYLE
MODIFICATIONS

? ~500 kcal restriction daily equates to weight reduction of 1 lb per week.
? Diets restricted in carbohydrate typically provide a rapid initial weight
loss.
? Adherence to the diet is more important than which diet is chosen.
? A high-quality diet— i.e., enriched in fruits, vegetables, whole grains,
lean poultry, and fish—should be encouraged to provide the maximum
overall health benefit.
DIET---

PHYSICAL ACTIVITY-
? 60–90 min of daily activity (At least 30 min.) Gradual increases in physical
activity should be encouraged to enhance adherence and avoid injury.
? Some high-risk patients should undergo formal cardiovascular evaluation
before initiating an exercise program.
? Physical activity could be formal exercise such as jogging, swimming, or
tennis or routine activities, such as gardening, walking, and housecleaning.

? Appetite suppressants-
phentermine and
sibutramine.
? Absorption inhibitors-
Orlistat
? Bariatric surgery is also
an option for patients
with BMI >40 kg/m2
or
>35 kg/m2
with
comorbidities.
OBESITY

? A fasting triglyceride value of <150 mg/dL is recommended. A
weight reduction of >10% is necessary to lower fasting
triglycerides.
? A fibrate (gemfibrozil or fenofibrate) is the drug of choice to
lower fasting triglycerides and typically achieve a 35–50%
reduction.
? Other drugs that lower triglycerides include statins, nicotinic acid,
and high doses of omega-3 fatty acids.
TRIGLYCERIDES

? For rise in HDL cholesterol, weight reduction is an important
strategy.
? Nicotinic acid is the only currently available drug with
predictable HDL cholesterol-raising properties.
? Statins, fibrates, and bile acid sequestrants have modest
effects (5–10%), and there is no effect on HDL cholesterol with
ezetimibe or omega-3 fatty acids.
HDL Cholesterol

LDL Cholesterol
For patients with the metabolic syndrome and diabetes, LDL
cholesterol should be reduced to <100 mg/dL.

BLOOD PRESSURE
? The direct relationship between blood pressure and all-cause
mortality rate has been well established.
? Best choice for the first antihypertensive should usually be an
angiotensin-converting enzyme (ACE) inhibitor or an angiotensin II
receptor blocker.
? In all patients with hypertension, a sodium-restricted diet enriched
in fruits and vegetables and low-fat dairy products should be
advocated.

? Insulin resistance is the primary Patho-physiologic mechanism for the
metabolic syndrome.
? Several drug classes [biguanides, thiazolidinediones (TZDs)] increase insulin
sensitivity.
? Both metformin and TZDs enhance insulin action in the liver and suppress
endogenous glucose production. TZDs, but not metformin, also improve
insulin-mediated glucose uptake in muscle and adipose tissue.
? Benefits of both drugs have also been seen in patients with NAFLD and PCOS,
and the drugs have been shown to reduce markers of inflammation and small
dense LDL.
INSULIN RESISTANCE

? Most patients with metabolic syndrome exhibit a prothrombotic state
characterized by elevations of plasminogen activator inhibitor-1 and
fibrinogen.
? Use of low dose aspirin can be recommended for patients with
metabolic syndrome, who have a high CV risk, those with overt type 2
diabetes mellitus, or atherosclerotic cardiovascular diseases.
? Metabolic syndrome frequently is accompanied by a pro-inflammatory
state, characterized by increased CRP levels. No specific treatment
available.
PROTHROMBOTIC &
PROINFLAMMATORY STATE

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metabolic syndrome and its clinical implications

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metabolic syndrome and its clinical implications

Editor's Notes