OVERWEIGHT AND OBESITY

Div. Endokrin-Metabolik
Departemen Penyakit Dalam FK USU/RSUP H Adam Malik Medan.

Defining obesity
Obesity - an excessive accumulation of body fat
sufficient to impair health
Risks - increase progressively from within the
healthy range

WHO 894 Obesity Report

Obesity: A Major Health Issue

Obesity is the No. 2 preventable cause of death and disability
(smoking is #1)
Obesity is associated with increased risk of heart disease, stroke,
gallbladder disease, cancer, osteoarthritis, sleep apnea
Obesity-related health problems cost $75 billion annually (2003
data)
The public pays about $39 billion a year -- or about $175 per
person -- for obesity through Medicare and Medicaid programs

Obesity is a Growing Problem

127 million adults in the U.S. are overweight, 60 million obese,
and 9 million severely obese.
64.5 percent of U.S. adults are overweight (BMI25)
30.5 percent are obese (BMI30)
4.7 percent are severely obese (BM40)

Media coverage of obesity

Adipose Tissue
White adipose tissue
Stored under the skin, in mesenteries and omentum, behind the
peritoneum
Primarily fat, also small amounts of protein and water
Stores triglycerides,
Brown adipose tissue
Large amounts in infants, small amounts in adults
Found primarily in scapular, sub-scapular areas
Heat production, cold adaptation, dissipation of excess energy

Adipose Tissue Mass vs. Function

Dysfunctional
adipose tissue
without increase in
mass

Normal
adipose tissue

Dysfunctional
adipose tissue
with increase in
mass
Increased number
of
enlarged
adipocytes

Dysfunctional
adipocyte

Abnormal cytokine production

Inflammation
NEFA

Systemic Insulin Resistance

Abnormal production of hormones

(Adipocytokines ) in fat
Type 2 DM

Lactate

Hypertension

Lipoprotein
Lipase

Angiotensinogen

Inflammation

Dyslipidemia

IL - 6

Arthritis
Asthma

Fat
Stores

Leptin

FFA

Insulin

Type 2 DM

TNF-
Adipsin
(Complement D)

ASCVD

Resistin
Estrogen

Adiponectin

Thrombosis
Plasminogen
Activator Inhibitor 1
(PAI-1)

DM=diabetes mellitus; FFA=free fatty acid; PAI-1=plasminogen activator inhibitor-1; TNF=tumor necrosis
factor alpha; IL-6=interleukin 6.
Slide: After Dr. G Bray

Adipocytokines
The term adipocytokines: adipocyte-derived biologically active
molecules which may influence the function as well as the
structural integrity of other tissues
Some examples of these substances are leptin, acylationstimulating protein (ASP), tumor necrosis factor-a (TNF-a),
plasminogen activator inhibitor-1 (PAI-1) and interleukin-6

Adipocytokines
Leptin is considered to be a fundamental signal of satiety to
the brain and has a variety of actions, ranging from
interference with sympathetic activity to hematopoiesis and
reproductive function
ASP increases triglyceride synthesis by increasing adipocyte
glucose uptake, activating diacylglycerol acyltransferase, and
inhibiting hormone-sensitive lipase

 TNF:

is involved in insulin resistance in obesity

PAI-1:

is a well-recognized causative factor for vascular

thrombosis

Resistin;

adipose-specific cysteine-rich protein with a

capacity to impair insulin sensitivity and glucose
tolerance in murine models

Adiponectin ; have anti-atherogenic and anti-inflammatory

properties

Weight
Weight is
is controlled
controlled by
by aa feedback
feedback system.
system.
Afferent

EC-CB1

Ghrelin
PYY
CCK

nn

Gut and Liver

Insulin

Pancreas

Leptin

Adipose Tissue

Adrenal Steroids

Adrenal Cortex

Efferent

Autonomic
Nervous
System

External Factors *
food availability,
palatability

Vagus
Nerve

Hypothalamus, etc

Meal Size
Energy
Balance
and
Adipose
Stores

Food Intake
Energy
Expenditure

Adiponectin

Aronne LJ. Adapted from Campfield LA, et al. Science. 1998;280:1383-1387; and Porte D, et al. Diabetologia. 1998;41:863-881.

Central Weight Regulating Mechanisms

Food intake
energy expenditure

food intake
energy expenditure

Science, Feb 7, 2003, Vol 299

Illustration by Katharine Sutliff

Estimation of Body Fat

Bioelectrical impedance
Low-energy current to the body that measures the resistance of
electrical flow
Fat is resistant to electrical flow; the more the resistance, the
more body fat you have
DEXA (dual x-ray photon absorptiometry)
An X-ray body scan that allows for the determination of body
fat
Infrared light
Assess the interaction of fat and protein in the arm muscle

Body Mass Index (kg/m2)

Dose - Response Risk Relationship
Underweight
< 18.5
Normal
18.5 - 25
Overweight
25 - 30
Obese
> 30
Class I
30 - 34.9
Class II
35 - 39.9
Class III
>40

BMI Criteria (WHO 2000)

Kategori

BMI (kg/m2)

BMI Asia

Underweight
Normoweight

< 18.5
18.5 - 24.9

< 18.5
18.5 - 22.9

Overweight:
Pre-obese

25
25.0 29.9

23
23.0 24.9

Obese I
Obese II

30.0 - 34.9
5.0 - 39.9

25.0 - 29.9
> 30.0

Obese III

40.0

Waist Circumference
Waist circumference, independent of BMI /
weight, confers additional health risk with:
Glucose intolerance / Diabetes mellitus
Hypertension
Dyslipidemia
Important - WC in any weight category confers
similar risk

Arch Intern Med 2002;162:2074

Regional Distribution

The regional distribution of body fat affects risk factors

for the heart disease and type 2 diabetes

Body Fat Distribution: Gynecoid

Lower-body obesity--Pear shape

Encouraged by estrogen and progesterone
Less health risk than upper-body obesity
After menopause, upper-body obesity appears

Body Fat Distribution: Android

Upper-body obesity--apple shape

Associated with more heart disease, HTN, Type II Diabetes
Abdominal fat is released right into the liver
Encouraged by testosterone and excessive alcohol intake
Defined as waist measurement of > 40 for men and >35 for
women

Causes of Obesity

Causes of Obesity
Set Point Theory
Genetics
If both parents are obese, then 80% risk that children are
obese.
If neither parent is obese, then risk is less than 10%
Twin studies Identical twins are more likely to weigh the
same as fraternal twins even when reared apart.
Food intake, tastes, BMR, number of fat cells, enzymes all
may be influenced by genetics.
Anthropologists have hypothesized are bodies are adapted to
storing fat due to times of famine.

Causes of Obesity (Continued)

Lipoprotein Lipase Enzyme which promotes fat storage in fat
cells and muscle cells.
Leptin Hormone which influences appetite and energy balance.
It increases satiety and energy. Ob gene has been found to code
for leptin.
Peptide PYY
Environmental Stimuli
Learned Behavior
Physical Inactivity

Obesity: Causes and

Consequences

Obesity
FFA
TG
HDL

Insulin resistance

Blood
pressure

Blood glucose
Type 2 diabetes

Cardiovascular
disease

Metabolic syndrome : The role of obesity.

Consequences of Obesity
Hypertension
Hypertension

Obesity

Sleep
Sleep Apnea
Apnea
Arthritis
Arthritis
Cardiovascular
Cardiovascular disease
disease
Social
Social disability
disability

Diabetes
Diabetes
Diabetes
Diabetes
complications
complications

Insulin
Insulin resistance/
resistance/
hyperinsulinemia
hyperinsulinemia
Cardiovascular
Cardiovascular
Disease
Disease

Hyperlipidemia
Hyperlipidemia

Role of obesity in insulin resistance

Caloric

Visceral
Obesity

intake

Free

fatty acids

Sedentary
lifestyle
Genetic
factors

Glucose
Lipids

Oxidative
stress
Inflammation

Insulin
resistance

Adapted from Wellen KE, Hotamisligil GS. J Clin Invest. 2005;115:1111-9.

Medical Complications of Obesity: Almost

every organ system is affected
Pulmonary disease
abnormal function
obstructive sleep apnea
hypoventilation syndrome
Nonalcoholic fatty liver
disease
steatosis
steatohepatitis
cirrhosis
Gall bladder disease
Gynecologic abnormalities
abnormal menses
infertility
polycystic ovarian syndrome
Osteoarthritis

Idiopathic intracranial hypertension

Stroke
Cataracts
Coronary heart disease
Diabetes
Dyslipidemia
Hypertension
Severe pancreatitis
Cancer
breast, uterus, cervix
colon, esophagus, pancreas
kidney, prostate

Skin
Gout

Phlebitis
venous stasis

Fat Cell Products and Hypertension

Visceral

Portal

Fat Stores

FFA

Hepatic

Insulin
Clearance

Vascular
Constriction
Angiotensinogen

Plasma

Insulin

Renal Na+

Reabsorption

Angiotensin II

Angiotensin I

Bray GA. Contemp Diagn Obes. 1998.

Hypertension

Obesity Prevention
and
Management

Therapy of weight loss:

1. Non pharamcological

2. Pharmacological

Non pharmacological therapy

of Weight loss
Diet
Exercise

i.e. Life style

modifications

Food Guide Pyramid

Health Benefits of Weight Loss

Decreased risk for cardiovascular disease.
Decrease glucose and insulin levels.
Decreased blood pressure.
Decreased LDL and triglycerides
Increased HDL.
Decrease in severity of sleep apnea.
Reduced symptoms of degenerative joint disease.

(Only in the US, from the Only in series)

Pharmacological therapy
of obesity

A Guide to Selecting Treatment

BMI Category
Treatment < 24.9
25-26.9
Diet, exercise,
behavior therapy
Pharmacotherapy
Surgery With co-

27-29.9

With co- With co-

30-35 35-39.9 >40

morbidities morbidities

With co-

morbidities

morbidities

Source: The Practical Guide to the Identification, Evaluation, and Treatment of Overweight and Obesity in Adults.

Obesity Pharmacotherapy
Approved for Long-Term Use
System

Mechanism

Examples

Digestive

Inhibition of lipase

Orlistat(Xenical)

CNS

Inhibit norepinephrine,

Sibutramine(Meridia)

serotonin and
dopamine reuptake

Approved for short-term use

CNS

Norepinephrine release

Phentermine, others

 absorption
of fat
Xenical
Chitosan

absorption of
CHO
Acarbose
Gymenemic
acid

Anorexic drugs
Sibutramine
energy
expenditure by
Sibutramine
gastric
emptying by
Acarbose

Conclusion
Overweight and obese individuals are more likely to
develop type 2 diabetes than their normal-weight
counterparts.
In addition, the incidence of insulin resistance,
hyperinsulinemia, and the insulin resistance syndrome is
greater as BMI increases.

This is the at
riskpatient
Im talking about