Bismillahi Allohumma sholli ‘ala Muhammad

Robbana zidna ‘ilman war zuqna fahma

Metabolic Syndrome &

Cardiovascular Disease
Relationships
A world wide pandemic
Dr Yuliana Rahmah, SpPD
Agenda
• Let’s praying first Robbana zidna
‘ilman nafi’an war zuqna fahma
• Introduction
• What is metabolic syndrome (Mets)?
• Pathogenesis of Mets ~ Cardiovascular
disease
• Management
• Summary
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 Pesan Langit
Wa maa asho-baka min
hasanatin famin Allah, wa
maa asho-baka min syayyi-
atin famin nafsika
Semua ni’mat datang dari Allah, semua
mushibah dari dirimu sendiri
[al Qur’an s. An-Nisaa’ (4): 79]

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 Introduction
• 1938 – Hinsworth coined insulin sensitivity
• 1960 – Yalow & Berson established obesity
w or w/o DM is a cause insulin resistance
• 1967 – Italian research group describes a
clustering of cardiovascular risk factors
(hypertension, diabetes, dyslipidemia, and
obesity)
• 1977 - German research group describes
ibid
• In 1988: insulin resistance and Syndrome X
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 Introduction
• 0besity (visceral, abdominal, android,
apple shape): [Insulin resistance,
hyperinsulinemia]
• IGT, T2DM
• Hypertension
• Dyslipidemia

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What is Metabolic
Syndrome?

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Metabolic Syndrome is …
• … a cluster of disorders  risk of
cardiovascular disease
 NHNES III (1988-1994): 8814 adults
American; overweight: 6.8% Mets;
obese: 28.7% Mets
 970 men w/o CAD, followed-up for 22 yrs;
hyperinsulinemia ~ major coronary events;
hazard ratios at 5, 10, 15, and 22 years 
2.3; 2.4; 1.8 and 1.3
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 Metabolic Syndrome
•“Syndrome X” / Syndrome X
•Multifaceted syndrome
•“Deadly quartet"
•Insulin resistance syndrome
•Dysmetabolic syndrome
•Cardiovascular metabolic syndrome
•Obesity dyslipidemia syndrome
• HONDA syndrome
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 HONDA Syndrome
• Hypertension
• Obesity
• NIDDM (T2DM)
• Dyslipidemia
• Atherosclerotic cardiovascular disease

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 Summary 1
• Prevalence of Mets is
increasing
• Mets has many names
• Mets is a cluster of risk for
cardiovascular disease

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 Criteria of
Metabolic Syndrome

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 WHO Criteria
DM, IGT, IFG, or insulin resistance plus
two or more of the following
1. High blood pressure: >160/90 mmHg
2. Hyperlipidemia: triglyceride concentration >150
mg/dl (1.695 mmol/l) and/or
3. HDL cholesterol <35 mg/dl (0.9 mmol/l) in men
and <39 mg/dl (1.0 mmol/l) in women
4. Central obesity: waist-to-hip ratio of >0.90 in men
or >0.85 in women and/or BMI >30 kg/m2
5. Microalbuminuria: urinary albumin excretion rate
>20 mg/min or an albumin-to-creatinine ratio
>20 mg/g.
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 ATP III Criteria
The metabolic syndrome if individuals
have three or more of the following
1. Abdominal obesity: waist circumference >102
cm in men and >88 cm in women
2. Hypertriglyceridemia: >150 mg/dl (1.7 mmol/l)
3. Low HDL cholesterol: <40 mg/dl (1.036 mmol/l)
in men and <50 mg/dl (1.295 mmol/l) in women
4. High blood pressure:>130/>85 mmHg
5. High fasting glucose: >110 mg/dl (>6.1 mmol/l)

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 Makassar Mets Criteria
The metabolic syndrome if individuals
have three or more of the following
1. Abdominal obesity: waist circumference >90 cm
in men, and >80 cm in women
2. Hypertriglyceridemia: >150 mg/dl (1.69 mmol/l)
3. Low HDL cholesterol: <40 mg/dl (1.036 mmol/l)
in men and <50 mg/dl (1.295 mmol/l) in women
4. High blood pressure:>130/>85 mmHg
5. High 2-hour glucose: >140 mg/dl (>7.8 mmol/l)

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 Syndrome X
• ~ Coronary artery diseases
• Hyperinsulinemia ~ major coronary event
(death or nonfatal myocardial infarction)
 Hazard ratios, at 5, 10, 15, and 22 years
 2.3, 2.4, 1.8, and 1.3
• Hyperinsulinemia ~ increases in both CV
and non-CV mortality
• Predictor of CAD in high LDL men

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 Pathogenesis of
Metabolic Syndrome ~
Cardiovascular Disease

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 Insulin Resistance
•decreased insulin-stimulated glucose
transport and metabolism in
adipocytes and skeletal muscle
•impaired suppression of hepatic
glucose output
•IGT and T2DM
• Genetic factor & environment

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 Fat Distribution
•Obesity ~ hypertension more common
•Hypertension >> severe in central
obesity
•Insulin resistance  hyperinsulinemia
 riskof IGT & DM
 Obesity  TNF-alpha  insulin resistance
 Gene mutation for the b3-adrenergic
receptor
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 Insulin Resistance
•Obesity  increased release of TNF-a
 insulin resistance
•Insulin resistance  hyperinsulinemia
 risk of IGT & DM
 gene mutation for the b3-adrenergic
receptor  increased
 risk for insulin resistance and obesity

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 Hypertension
• Hyperinsulinemia
 enhances activity of sympathetic system
 sympathetic-induced hypertension
  stimulates renal sodium reabsorption
 vasodilatation effect is blunted in obesity
 up-regulation of A-II type 1 receptors

Relationship between insulin

and hypertension is not
confirmed
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 Obesity ~ T2DM
• Sampun kasohor dosoan taun
• Obesity ~ insulin resistance (IR)
 Ethnicity
 Body weight
 Age
 Both sexes
• IR rises along with body fat content 
central (intra-abdominal, visceral, apple
shape, android) obesity ~ insulin resistance
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Prevalence of T2DM by Ethnicity

Harris et al. 1998 Diabetes Care 21: 518-24 22

Harris et al. 1998 Diabetes Care 21: 518-24 23
Insulin Sensitivity ~ Body Mass
Index Relationship

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Insulin Sensitivity ~ Visceral
Obesity Relationship

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Insulin ~ Visceral Obesity
• Abdominal fat is more lipolytically active
than subcutaneous fat, perhaps because of
its greater complement of adrenergic
receptors
• Abdominal adipose store is resistant to the
anti-lipolytic effects of insulin  greater flux
of fatty acids into the circulation

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Tissue uptake of glucose in nondiabetic and
insulin resistant diabetic subjects during a
hyperinsulinemic-euglycemic clamp

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Other factor

Hyperinsulinemia
Hypertension IGT & Diabetes
Insulin resistance

PPAR
Dyslipidemia Obesity
Adipogenesis

High CH Diet Genetic background Sedentary life

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 Summary 2
Mets ~ Cardiovascular Disease
•Insulin resistance  hyperinsulinemia
•Hypertension
•Obesity, esp. abdominal (central, male
type, apple-shape, android, visceral)
•NIDDM (IGT, Diabetes)
•Dyslipidemia

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Management of
Metabolic Syndrome

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 Management
• Medical evaluation: age at onset,
recent weight changes, family history of
obesity, occupation, eating and exercise
behavior, cigarette and alcohol use,
psychosocial factors
• Multidisciplinary approach: Behavioral
modification  hypocaloric diets,
 increased energy expenditure, and
 addition of pharmacological therapy
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 Management
• Mulut kamu harimau kamu
•Weight loss  Shiyam
•Regular physical exercises  five
times sholat

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 Summary 3
Mets ~ Cardiovascular Disease
•Mets increased risk of cardiovascular
disease through several mechanisms
•All of which can be treated or
Tawakkal ‘ala Allah
• Thank you for your attention

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