OBESity

Yuanita Asri Langi

Pathophysiology of Obesity ??

Energy Energy
Intake Expenditure
• Lavoisier & Laplace (1783) :
 Energy balance ( food intake versus energy
output) is physiologically regulated .
• Postulated : The energy balance in mammals to
be controlled by a feedback loop in which the
amount of stored energy is sensed by the
hypothalamus, which adjusts food intake and
energy expenditure to maintain a constant body
weight.
• The nature of the inputs to the hypothalamus
was unclear
Nature 1994 ;372: 425-432
Positional cloning of the mouse obese gene and its
human homologue
Yiying Zhang , Ricardo Proenca , Margherita Maffei , Marisa Barone
Lori Leopold & Jeffrey M. Friedman (1994)

 Obese (Ob) gene regulates energy balance in the mouse .

 Mutation of Ob gene results in profound obesity and type Il
diabetes as part of a syndrome that resembles morbid
obesity in humans.

 The Ob gene product ( leptin ) may function as part of a

signaling pathway from adipose tissue that acts to regulate

the size of the body fat depot.
Nature 1994 ;372: 425-432
Physiological Metabolic Energy Cell Signalling Biology - Michael J. Berridge -
Network www.cellsignallingbiology.org - 2012
 Trends Endocrinol Metab. 2010 Nov;
21(11): 643–651.

Mechanisms that contribute to food intake

 Trends Endocrinol Metab. 2010 Nov;
21(11): 643–651.

Increases feeding by increasing the drive to eat

 Trends Endocrinol Metab. 2010 Nov;
21(11): 643–651.

New equilibrium for food intake in the continued presence of

increased food palatability/availability
Causes of Obesity ?
Energy
Intake

Energy
Expenditure

nutritional, activity levels,

endocrine, genetic
Obesity as disease
and
risk of diseases
 Obesity
• A disease with multiple pathophysiological aspects, including:
 Genetic
 Environmental
 Physiological
 Psychological

• Sets the framework for future efforts from many stakeholders to

advance its treatment and prevention.

The American Association of Clinical Endocrinologists (AACE) 2012 . ENDOCRINE PRACTICE Vol 18 No. 5 September/October
 Diagnosis and
Management Of Obesity
The AACE Advanced Framework for a New
Diagnosis of Obesity
Anthropometric
DIAGNOSIS Clinical Component
Component
BMI ≥ 23 – 29.9 No obesity-related
Overweight
kg/m2 complications
No obesity-related
Obesity BMI ≥ 30 kg/m 2
complications

Presence of one or more

Obesity
BMI ≥ 23 kg/m2 mild-to-moderate obesity
Stage 1
related complications
Presence of one or more
Obesity severe obesity related
Stage 2 BMI ≥ 23 kg/m2 complications
Endocr Pract. 2014 September; 20(9): 977–989
Staging of Obesity-Related Complications That Can Be
Improved by Weight Loss ( AACE 2014)

Prediabetes, Metabolic Syndrome, and Type 2 Diabetes.

No risk factors related to insulin resistance (WC,

 Stage 0 (none) BP, HDL, TG, fasting Glucose). This is equivalent
to Cardiometabolic Disease Stage 0 (CMDS)

Stage 1 (mild- 1 or 2 risk factors (WC, BP, HDL, TG; CMDS

moderate) stage 1)

  Stage 2 (severe) Prediabetes, Metabolic Syndrome, or Type 2

Diabetes (CMDS stages 2–4)
Staging of Obesity-Related Complications That Can Be
Improved by Weight Loss ( AACE 2014)
Hypertension

Stage 0
Blood Pressure < 130/85 mm/Hg
(none)

Stage 1 (mild- BP ≥ 130/85 mm/Hg in absence of

moderate) other risk factors

BP target not met despite use of anti-

hypertensive medication(s)
Stage 2
BP ≥ 130/85 mm/Hg in high risk
(severe
individual: CMDS 2–4, smoking,
complication)
African American, congestive heart
failure
Staging of Obesity-Related Complications That Can Be
Improved by Weight Loss ( AACE 2014)
Hypertriglyceridemia/Dyslipidemia
Stage 0 TG < 150 and HDL-c ≥ 40 in male and
(none) ≥ 50 in female
TG 150–399 and/or HDL-c < 40 in
Stage 1 (mild-
male and < 50 in female in absence of
moderate)
other risk factors
TG ≥400 in absence of other risk
Stage 2 factors
(severe TG ≥ 150 and HDL-c < 40 in male and
complication) < 50 in female in high risk
individual: CMDS stage 2–4
Initial evaluation in patients with Obesity
(BMI ≥ 23 kg/m2), AACE 2014

 history, physical examination,

 review of systems, blood pressure, waist
circumference,
 fasting glucose, fasting lipid panel (total
cholesterol, LDL-c, HDL-c, triglycerides),
 creatinine, and hepatic transaminases.
Self learning :
Describe the Staging of Obesity-Related
Complications That Can Be Improved by Weight Loss
(AACE 2014) of :
Sleep Apnea, NALF, PCOS, OA, Stress and Urge
Urinary Incontinence, GERD, Disability/Immobility,
Psychological Disorder/Stigmatization, Other
Complications
AACE 2014
> 23, WC:  < 23, WC : N
AACE/ACE Obesity CPG, Endocr Pract. 2016;22(Suppl 3)
Metabolic Syndrome
 Practice Definition
 Metabolic syndrome is a multiplex risk factor that
arises from insulin resistance accompanying
abnormal adipose deposition and function.
 It is comprised of a combination of risk factors for
coronary heart disease, as well as for diabetes,
fatty liver, and several cancers.

https://emedicine.medscape.com/article/165124-overview
 Insulin Resistance Syndrome
(Metabolic Syndrome)

Glucose
Intolerance

Hypertension Dyslipidemia
(High TG, Low HDL)
Insulin
Resistance
PCOS
Cardiovascular
Disease
Obesity
Acanthosis Nigricans

Hyperpigmented, velvety
patches of skin in
axillary regions and neck
(typically).
 Diagnosis
of
Metabolic Syndrome
Waist circumference
and the metabolic syndrome
 The presence of abdominal obesity is more highly correlated
with the metabolic risk factors than is an elevated BMI.
 The new IDF consensus definition of the metabolic syndrome
stipulates the following as a pre-requisite for
a diagnosis of metabolic syndrome:

≥ 80 cm for Indonesian women

≥ 90 cm for Indonesian men

Waist circumference is calculated by comfortably measuring

the waist halfway between the bottom of the rib cage and the
top of the pelvis.
Intra-abdominal adiposity is closely
correlated with abdominal obesity
300
r = 0.80

200

IAA (cm2)
100

IAA
0
60 80 100 120
Waist circumference (cm)
To assess IAA, the simplest measure of abdominal obesity is waist
circumference, which is strongly correlated with direct measurement of IAA
by CT scan or MRI, considered to be the gold standard

IAA: intra-abdominal adiposity; CT: computed tomography;

MRI: magnetic resonance imaging
Després JP et al, 2001; Pouliot MC et al, 2004
Metabolic syndrome:

The NCEP ATP III definition*

In order to make a diagnosis of the metabolic syndrome a
patient must present with three or more of the following
five risk factors:
Risk Factor Defining Level
Abdominal obesity Waist circumference
Men >102 cm (>40 in)
Women >88 cm (>35 in)
Triglycerides ≥150 mg/dL (1.7 mmol/L)
HDL cholesterol
Men <40 mg/dL (1.04 mmol/L)
Women <50 mg/dL (1.29 mmol/L)
Blood pressure ≥130/ ≥85 mmHg
Fasting glucose ≥100 mg/dL (5.6 mmol/L)

*2001, updated 2005

Type 2 diabetes,
the metabolic syndrome and
cardiovascular disease in Europe
Metabolic syndrome:
IDF consensus definition (2005)
Central Obesity
Waist circumference - ethnicity specific*
- for Europids: Male ≥ 94 cm
Female ≥ 80 cm
plus any two of the following:
Raised Triglycerides ≥150mg/dL (1.7mmol/L)
or specific treatment for this lipid abnormality

Low HDL Cholesterol <40mg/dL (1.03 mmol/L) in males

<50mg/dL (1.29 mmol/L) in females
or specific treatment for this lipid abnormality

Raised blood pressure Systolic : ≥130 mmHg or

Diastolic: ≥85 mmHg or
Treatment of previously diagnosed hypertension

Impaired fasting Fasting plasma glucose ≥100 mg/dL (5.6 mmol/L)

glycaemia or previously diagnosed type 2 diabetes
If above 5.6 mmol/L or 100 mg/dL, OGTT is strongly recommended
but is not necessary to define presence of the syndrome.
Type 2 diabetes,
the metabolic syndrome and
cardiovascular disease in Europe
 Management
of
Metabolic Syndrome
 First line therapy : Therapeutic lifestyle change, with
emphasis on weight reduction.
 In patients in whom lifestyle changes fail to reverse
metabolic risk factors, consideration should be given
to treating specific abnormalities in these risk factors
with drugs.
 Use of drugs to target risk factors should be in
accord with current treatment guidelines.
meralday@yahoo.co.id