OBESITAS, SINDROMA METABOLIK DAN

PERMASALANNYA

A. MAKBUL AMAN MANSYUR

Division of Endocrine and Metabolism, Department of Internal Medicine
Faculty of Medicine Hasanuddin University /
RS. UNHAS / RS Dr. Wahidin Sudirohusodo
 Introduction
• Obesity is a chronic disease of multiple etiologies
characterized by the presence of excess adipose tissue
• Traditionally defined as a weight 20% greater than ideal
body weight
• Medical condition responsible for serious co-morbidity and
mortality → major public health problem across the world.
• Obesity results from excessive caloric intake, decreased
energy expenditure and/or from a combination of the two.
 Type of Obesity

APPLE TYPE :Central or

abdominal adiposity (ANDROID) → PEAR TYPE : GYNOID or typical
increased WHR & associated with female distribution of fat : less
higher morbidity risk. ♂ > ♀ health risks
 Causes of Obesity
• Heredity • Physical inactivity
• Familial • Dietary intake
• Demographic factors
• Smoking cessation
age
gender • Drugs ( steroids, lithium,
ethnicity sulphonylureas)
social class • rarely endocrine disorders
marital status
Today’s
Older environment
environments: provides afood
an unreliable constant
supplysupply
& highof need
high for
energy
physical
food with
activity
reduced
to procure
needsfood
for physical
to survive.
activity.
 Eat to

Intake = Expenditure Intake > Expenditure

Weight Stable Obese

Live to Eat!
Live!
The physiology of weight gain
 Indeks Massa Tubuh (IMT)
Berat Badan (kg)
Tinggi Badan2 (m2)

Classification BMI (kg/m2) Risk of co-morbidities

Underweight 18,5 Low ( but Increased

risk of other clinical problems)
Mengukur kelebihan
Normal Range 18,5 - 22,9 Average
massa lemak tubuh
Overweight > 23
At Risk 23 - 24,9 Increase
Obese I 25 - 29,9 Moderate
Obese II > 30 Severe
LINGKAR PINGGANG

NORMAL:
Laki –laki < 90 Cm
Wanita < 80 Cm
 Psychosocial consequence
• Economical impact of obesity
• Prejudice and Discrimination
• Considered lazy, incompetent and more often
absent due to illness
• Confronted with more problems at job application
 Medical Consequence of Obesity
Pulmonary disease Idiopathic intracranial
abnormal function hypertension
obstructive sleep apnea Stroke
hypoventilation syndrome
Cataracts
Nonalcoholic fatty liver Coronary heart disease
disease
Diabetes
steatosis
steatohepatitis Dyslipidemia
cirrhosis Hypertension

Gall bladder disease Severe pancreatitis

Gynecologic abnormalities Cancer

abnormal menses breast, uterus, cervix
infertility colon, esophagus, pancreas
polycystic ovarian syndrome kidney, prostate

Osteoarthritis
Phlebitis
Skin venous stasis
Gout
 Obesity and Clinical Consequences

Type 2 diabetes and

glycemic disorders

METABOLIC
SYNDROME

Atherosclerosis
Dyslipidemia
Insulin
resistance – Low HDL
– Small, dense LDL
Visceral Glucotoxicity – Hypertriglyceridemia
Obesity Lipotoxicity Hypertension

Endothelial dysfunction/
inflammation (hsCRP)

Impaired thrombolysis
 PAI-1

Courtesy of Selwyn AP, Weissman PN.

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

Alternative names
Metabolic syndrome, Syndrome X, Insulin
resistance syndrome, the Deadly quartet,
Reaven’s syndrome
 Metabolic Syndrome: Overview
• Metabolic Syndrome is not a disease, but rather a
cluster of disorders of our body’s metabolism, including:
o High blood pressure
o High insulin levels
o Excess body weight
o Abnormal cholesterol levels

• Each of these disorders is by itself a risk factor for

other diseases.
• In combination, however, these disorders dramatically
boost the chances of developing potentially life-
threatening illnesses, such as diabetes,
heart disease or stroke.
DYSLIPIDEMIA INSULIN
RESISTANCE

OBESITY
HIGH
BLOOD
PRESSURE
DROP
The major features of
metabolic syndrome
 DIAGNOSIS MS
NCEP- ATP III criteria

Risk Factor Defining Level

Abdominal obesity†
(Waist circumference‡)
Men >90 cm
Women >80 cm
TG 150 mg/dL or Rx for ↑ TG
HDL-C
Men <40 mg/dL
Women <50 mg/dL or Rx for ↓ HDL
Blood pressure 130/85 mm Hg or on HTN Rx
Fasting glucose 100 mg/dL or Rx for ↑ glucose
*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.
 DIAGNOSIS
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
 TREATMENT

• Management needs to be flexible and

integrate different therapeutic approaches
according to individual patient needs,
including:
– Dietary management
– Lifestyle modification
– Physical activity
– Drug therapy
– Surgery
 LIFESTYLE
MODIFICATIONS

• Weight reduction- include a combination of caloric

restriction, increased physical activity, and behavior
modification.
Mortality Diabetes
> 20% in total mortality  50% in fasting glucose
> 30% in diabetes – realated deaths Lipids
> 40% in obesity – related cancer deaths  of 10% total cholesterol
Blood Pressure  of 15% LDL
 10 mmHg systolic  of 30% triglycerides
 20 mmHg diastolic  of 8% HDL

Physician’s guide to the management of obesity with Xenical. Xenical Orlistat: p. 13

 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.
 Management objectives
• Promotion of weight loss
• Long-term weight maintenance
• Long-term prevention of weight regain
• Improvement of risk factors
• Encouragement of active lifestyle
• Improvement in quality of life
• Change in eating patterns
• Consider healthier weight over time -
not ideal weight
 Lifestyle/Diet
• Caloric reduction will cause weight loss
• Estimated caloric deficit of 3500 kcal = 1 lb (0.45 kg) of fat
• Usual target is dietary reduction of 500 kcal/day to achieve a
deficit of 3500 kcal/week (15% protein, 30% fat)
• Goal: steady sustainable dietary change
• No single dietary approach is especially effective, and there is
considerable variability in the response of individuals to dietary
intervention
• A nutritionally balanced diet designed to reduce energy intake
should be combined with other supportive interventions to promote
sustainable energy deficits and to ensure the maintenance of weight
loss
• Dietitians and patients need to work together to determine the
optimal dietary plan on an individual basis to promote sustainable
weight loss
 Weight Loss: The Recommendations
-Goal is to reduce body weight by 10% over 6 months
-BMI 27 – 35: 300 – 500 kcal deficit daily → ½ to 1 lb per wk loss
-BMI > 35: 500 – 1000 kcal deficit daily → 1 to 2 lb per wk loss
-Low calorie diet with dietary fat < 30% of total calories
-Sustained physical activity recommended.

Fasting for wt loss?

• Fasting is popular because it can provide dramatic
weight-loss but it is primarily water rather than fat
• Lost water is regained quickly when eating is resumed.
• Prolonged fasting is not recommended and may lead to
nutritional imbalances
 Individual
eventually
reaches a
weight loss
plateau, loses
motivation, and
returns to old
eating habits !
Specific Treatment (drugs)
 OBESITY

• 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.
 TRIGLYCERIDES

• 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.
 HDL Cholesterol
• 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.
 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

• 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.
 GLYCEMIC
CONTROL
• In patients with the metabolic syndrome and Type 2 diabetes,
aggressive glycemic control decreases cardiovascular risk..

• In patients with IFG without a diagnosis of diabetes, a lifestyle

intervention has been shown to reduce the incidence of Type 2
diabetes.

• Metformin has also been shown to reduce the incidence of

diabetes, although the effect was less than that seen with
lifestyle intervention.
 PROTHROMBOTIC &
PROINFLAMMATORY
STATE
• 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.
 In Conclusions
OBESITY - METABOLIC SYNDROME

The Two Terrorists

 The Compound Jeopardy !!
Insulin Resistance

Obesity MS with HT associated Diabetes

2x 4x

CAD, CKD, PAD, CVD – All same

Reilly MP et al – Circulation 2003; 108: 1546-1551

What to do..?
Thank you for your attention