Dr. Sharanya Rajan's document defines obesity and discusses its epidemiology. Key points include: - Obesity is defined as a BMI ≥ 30 and is caused by an imbalance between energy intake and expenditure. - Over 1.6 billion adults are overweight globally, with 400 million obese. Obesity is more common in women and increasingly affects poorer populations. - Hypothalamic and genetic factors contribute to obesity development. Conditions like Prader-Willi syndrome, leptin/leptin receptor deficiencies, and POMC/MC4R mutations can cause monogenic obesity. - Adipokines like leptin and resistin, as well as gut and pancreatic hormones, help regulate

1. OBESITY AWARENESS
Dr Sharanya Rajan

2. DEFINITION
 Latin word ―OBESUS‖meaning stout, fat, plump.
 It is defined as a state of excess adipose tissue.
 BMI ≥ 30

3. OBESITY VS OVERWEIGHT
Overweight – Fat
Fluid
Muscle mass
Bone
Tumours
Obesity – Fat ( adipose tissue )

4. EPIDEMIOLOGY
 >1.6 billion overweight of which 400 million are
obese
 Women > men
 More common even in poor
States Males (%) Males rank Females (%) Females rank
India 12.1 14 16 15

5. States Males (%) Males rank Females (%) Females rank
Punjab 30.3 1 37.5 1
Kerala 24.3 2 34 2
Goa 20.8 3 27 3
Tamil Nadu 19.8 4 24.4 4
Andhra Pradesh 17.6 5 22.7 10
Sikkim 17.3 6 21 8
Mizoram 16.9 7 20.3 17
Himachal
Pradesh
16 8 19.5 12
Maharashtra 15.9 9 18.1 13
Gujarat 15.4 10 17.7 7
Haryana 14.4 11 17.6 6
Karnataka 14 12 17.3 9
Manipur 13.4 13 17.1 11
Uttarakhand 11.4 15 14.8 14

6. REGULATION OF APPETITE
 Appetite – lateral hypothalamus
 Satiety – ventromedial hypothalamus
Destruction of LHA leads to starvation and death.
Destruction of VMA leads to obesity.

7. OTHER CENTRES IN REGULATION OF APPETITE :
primary1. Arcuate Nuclei-
site for action of leptin and insulin.
2. Para Ventricular Nuclei-
AMP kinase mediated appetite regulation
3. Dorsomedial Hypothalamic Nuclei-
destruction leads to hyperphagia and obesity

8. NEURO HUMORAL FACTORS IN OBESITY
 Adipokines – Leptin, Resistin, Adiponectin, Retinol
binding Protein 4, Visfatin
 Pancreatic hormones – Insulin, Pancreatic
Polypeptide (PP/PYY/NPY)
 Gut Hormones - Incretins

9. LEPTIN
 Leptin acts on receptors in the hypothalamus of the
brain where it:
1. counteracts the effects of neuropeptide Y (a
potent feeding stimulant secreted by cells in the
gut and in the hypothalamus);
2. counteracts the effects of anandamide (another
potent feeding stimulant that binds to the same
receptors as THC, the active ingredient of
marijuana)
3. promotes the synthesis of α-MSH, an appetite
suppressant;
RESULT- inhibition of food intake.

10. LEPTIN
Increase leptin
Increased Melanocortin receptor signal
Increased
POMC
Increased alpha-MSH
DecreasedAppetite
PC 1

11. LEPTIN
 This inhibition is long-term, in contrast to


Cholecystokinin(CCK)- the rapid inhibition
PPY- the slower suppression of hunger
between meals
 Leptin also acts on hypothalamic neurons
responsible for :


the secretion of gonadotropin-releasing
hormone (GnRH).
stimulating the sympathetic nervous system
to modulate the balance between the
formation and breakdown of bone.

12. LEPTIN
In addition to its effect on the hypothalamus, leptin
acts directly on:
 the cells of the liver and skeletal muscle where it
stimulates the oxidation of fatty acids in the
mitochondria. This reduces the storage of fat in
those tissues (but not in adipose tissue).
 T cells where it enhances the production of Th1
cells promoting inflammation.

13. LEPTIN

14. RESISTIN
 In humans, Resistin is primarily a product of
macrophages, not fat cells.
 Resistin causes insulin resistance
 There is a strong association in humans between
elevated levels of Resistin, Obesity, and Type 2
diabetes
 over 80% of the people with NIDDM are obese

15. ADIPONECTIN
 Its circulating levels are 1000 fold higher than leptin
or insulin.
 It plays a role in increasing energy expenditure and
decreasing body weight also increases insulin
sensitivity
 Thiazolidinediones increase this hormone via
PPAR-gamma
 Its level are increased after starvation.

16. RETINOL BINDING PROTEIN 4
When it is secreted in elevated amounts by fat cells, it
:
1. Suppresses glucose uptake by skeletal muscle;
2. Enhances glucose release by the liver.
 These actions counteract those of insulin.
 Elevated levels of RBP4 occur in humans with Type
2 diabetes mellitus.

17. VISFATIN
 Produced by visceral fat
 Increase in response to fatty diet
 Role in adipose differentiation

18. PANCREATIC HORMONES
 Plasma PP are inversely co related with adipocity
 Patients with Prader Willi have decrease amount of
PP

19. GUT HORMONES
 PYY-
1. Secreted from L cells of GI tract
2. Reduces food intake
 Ghrelin-
1. mainly secreted from stomach
2. A potent Orexigenic
 Cholecystokinin
1. Mainly secreted in duodenum
2. Decreasing meal size and duration both.

20. ADIPOSE
TISSUE
Tnf alpha
IL 6 PAI 1
Decrease
GLUT 4
Impaired signal
transduction of
insulin
atherosclerosis
Impaired insulin
signalling
Decrease NO
mediated vaso
dilatation
INSULIN
RESISTANCE

21. ETIOLOGY OF OBESITY
 A heterogeneous group of disorders
 Complexity of neuroendocrine and metabolic
syndromes regulate energy intake, storage and
expenditure.
 Obesity is caused by imbalance between energy
intake and expenditure.
 Obesity runs in families
 Inheritance is not mendelian.

22. ETIOLOGY OF OBESITY- TWIN STUDIES
 Identical twins have similar BMIs
 High concordance between monozygotic twins
compared to dizygotic twins
 correlations did not differ significantly between
twins reared apart and twins reared together

23. ETIOLOGY OF OBESITY- ADOPTION STUDIES
 Strong relationship between the BMI of adoptees
and biological parents.

24. PLEIOTROPIC OBESITY SYNDROMES
 Autosomal dominant
Ulnar Mammary Syndrome: 12q24
Other features- Ulnar defects, delayed puberty,
hypoplastic nipples.

26. PLEIOTROPIC OBESITY SYNDROMES
 Autosomal Recessive
• Alstrom syndrome : 2p13
Other features-. Retinal dystrophy, neurosensory
deafness, diabetes
• Cohen syndrome : 8q22
Other features- Prominent central incisors,
opthalmopathy, microcephaly

27. PLEIOTROPIC OBESITY SYNDROMES
 Autosomal Recessive
• Carpenter syndrome :
(Acrocephalopolysyndactyly)
Other features- acrocephaly, polydactyly, genu
valgum, secondary hypogonadism.
• Laurence Moon Biedl syndrome:
Other features-short stature with primary
hypogonadism and onset at 1 – 2 years

29. PLEIOTROPIC OBESITY SYNDROMES
 X linked
•Borjeson-Forssman-Lehmann syndrome : Xq26
Other features- Mental retardation, hypogonadism,
large ears
• Mehmo syndrome : Xp22
Other features- Mental retardation, epilepsy,
hypogonadism, microcephaly

30. PLEIOTROPIC OBESITY SYNDROMES
 X linked
• Simpson-Golabi-Behmel - type 2 : Xp22
Other features- Craniofacial defects, skeletal and
visceral abnormalities
• Wilson-Turner syndrome : Xp21
Other features- Mental retardation, tapering fingers,
gynaecomastia

31. PRADER WILLI SYNDROME
 Most common syndromal cause of human obesity
 Prevalence of about 1 in 25,000
 uniparental maternal disomy(15q11.2-q12 )
 Caused by deletion or disruption of a paternally
imprinted gene on the proximal long arm of
chromosome 15.
 Characterized by diminished foetal activity, obesity,
hypotonia, mental retardation, short stature,
hypogonadotropic hypogonadism, and small hands
and feet
 Hyperphagia is a dominant feature in PWS

33. PRADER WILLI SYNDROME
 diminished growth
 reduced muscle mass (lean body mass)
 increased fat mass - body composition
 hypogonadotrophic hypogonadism
 Fasting plasma ghrelin levels are 4.5-fold higher in
PWS subjects

35. ALBRIGHT HEREDITARY OSTEODYSTROPHY
 AHO is an autosomal dominant disorder
 Germline mutations in GNAS1
 Decrease expression/function of G alpha s protein.
 short stature, obesity, skeletal defects, and
impaired olfaction.

37. FRAGILE X SYNDROME
 extreme obesity (no hypotonia = pws)
 a full, round face
 small, broad hands and feet
 regional skin hyperpigmentation
 severe mental retardation
 macro-orchidism
 large ears
 prominent jaw
 and high-pitched jocular speech

38. BARDET BIEDL SYNDROME
 AUTOSOMAL RECESSIVE DISEASE
 OBESITY
 MENTAL RETARDATION
 DYSPHORMIC EXTREMITIES
(SYNDACTYLY, BRA OR POLYDACTYLY)
 RETINAL DYSTROPHY OR PIGMENTARY
RETINOPATHY
 HYPOGONADISM OR HYPOGENITALISM (LIMITED
TO MALE PATIENTS)
 STRUCTURAL ABNORMALITIES OF THE KIDNEY
chydactyly

39. MONOGENIC HUMAN OBESITY
 In the past five years several human disorders of
energy balance that arise from genetic defects have
been described.
 Mutations all result in morbid obesity in childhood
without the developmental pleiotropic features
characteristic of the recognised syndromes of
childhood obesity.

40. INCREASE LEPTIN
Increased Melanocortin receptor signal
Increased
POMC
Increased alpha-MSH
DecreasedAppetite
PC 1
leptin receptor
Decreased
AgRP

41. CONGENITAL LEPTIN DEFICIENCY
 The first monogenic human obesity syndrome.
 Homozygous for a frameshift mutation in the ob
gene (ob/ob)
 Hyperphagic-constantly demanding food
 An intense drive to eat-never satisfied.
 They developed severe disabling obesity (an 8yr
old girl weighing 86kg and a 2yr old boy weighing
29kg)
 Advanced skeletal maturation
 Impaired T cell mediated immunity
 Hypogonadotropic hypogonadism

42. CONGENITAL LEPTIN DEFICIENCY

44. CONGENITAL LEPTIN DEFICIENCY
 The administration of leptin to leptin-deficient ob/ob
mice results in a decrease in food intake, weight
loss and restoration of fertility and T cell mediated
immune function.
 Leptin-deficient children have been treated with
daily subcutaneous injections of recombinant
human leptin for up to four years with sustained,
beneficial effects on appetite, fat mass,
hyperinsulinaemia and hyperlipidaemia.

46. LEPTIN RECEPTOR DEFICIENCY
 consanguineous family
 loss of the leptin receptor results in a more diverse
phenotype than loss of its ligand leptin.
 normal birthweight
 exhibited rapid weight gain in the first few months of
life
 aggressive behaviour when denied food
 decreased IGF-1 and IGF-BP3 levels
 hypothalamic hypothyroidism

47. INCREASE LEPTIN
Increased Melanocortin receptor signal
Increased
POMC
Increased alpha-MSH
DecreasedAppetite
PC 1
leptin receptor
Decreased
AgRP

48. POMC DEFICIENCY
 Pro-opiomelanocortin (POMC) is produced by
hypothalamic neurones of the arcuate nucleus
 presented in neonatal life with adrenal crisis due to
isolated ACTH deficiency
 hyperphagic, developing early-onset obesity
 pale skin and red hair due to the lack of MSH
function

50. INCREASE LEPTIN
Increased Melanocortin receptor signal
Increased
POMC
Increased alpha-MSH
DecreasedAppetite
PC 1
leptin receptor
Decreased
AgRP

51. PROHORMONE CONVERTASE 1 DEFICIENCY
 childhood obesity
 abnormal glucose homeostasis
 very low plasma insulin
 elevated levels of pro insulin
 hypogonadotropic hypogonadism
 hypocortisolaemia
 elevated levels of POMC

52. INCREASE LEPTIN
Increased Melanocortin receptor signal
Increased
POMC
Increased alpha-MSH
DecreasedAppetite
PC 1
leptin receptor
Decreased
AgRP

53. MELANOCORTIN 4 RECEPTOR DEFICIENCY
 Mutations in the MC4R appear to be the
commonest monogenic cause of obesity
 increase in lean body mass
 Increased bone mineral density
 increased linear growth throughout childhood
 hyperphagia
 severe hyperinsulinaemia

55. INCREASE LEPTIN
Increased Melanocortin receptor signal
Increased
POMC
Increased alpha-MSH
DecreasedAppetite
PC 1
leptin receptor
Decreased
AgRP

56. AGRP DEFICIENCY
 AgRP antagonizes alpha MSH action
 So deficiency leads to overexpression of MC4R
receptor.

57. OTHER MOLECULAR DEFECTS
 TUB gene – late onset Obesity
 FAT gene – obesity by disruption of neuropeptides.

58. ENDOCRINAL ABNORMALITIES-
CUSHING SYNDROME
 Increased cortisol production
 Hypertension
 Glucose intolerance
 Cushingoid facies

59. ENDOCRINAL ABNORMALITIES-
HYPOTHYROIDISM
 Uncommon cause of obesity
 Much of weight gain is due to Myxedema
 Ruled out by serum TSH.

60. ENDOCRINAL ABNORMALITIES-
INSULINOMA
 In order to avoid hypoglycemia patients often eat
more leading to weight gain.
 High insulin promote fat genesis.

61. ENDOCRINAL ABNORMALITIES-
SYNDROME X
 Central obesity
 Glucose intolerance
 Dyslipidemia
 hypertension

62. ENDOCRINAL ABNORMALITIES-
PCOD
 2 out 3 criteria for diagnosis
1) Menstruation irregularities due oligo/an
ovulation(progesterone level at 21st day of cylcle)
2) Clinical or biochemical evidence of
hyperandrogenism.
3) USG s/o ovarian cysts.

63. CRANIOPHARYNGIOMA-OTHER DISORDERS OF
HYPOTHALAMUS
 Tumours
 inflammation
 trauma
 GH decreases but Somatomedin is normal.

64. VIRAL ETIOLOGY ??
 Virus SMAM-1 – in chicken.
 Virus Ad-36 found almost exclusively in obese
human beings
 The mechanism by which Ad-36 causes obesity is
unclear.
 It can be hypothesized that hypothalamic damage
caused by viruses might be a cause.

65. MEASUREMENT OF OBESITY
 BMI
 Waist hip ratio
 Skin fold thickness
 Biometric impedance
 Ultrasound
 DEXA (Dual Energy XrayAbsorptiometry
 CT / MRI
 Air displacement Plethysmography
 Total body electrical conductivity
 Hydrometry (most accurate)

66. BODY MASS INDEX (BMI)
 Calculated as Weight(kg)/Height(m^2)
 Correlation between rise in BMI and Complications.
 BMI measures individual’s total weight relative to its
height.
 BMI may be high in a vey muscular person
 For similar BMIs women have greater fat mass than
their male counterparts
 So BMI may be misleading in certain cases

67. BMI PRIME
 BMI Prime - A simple modification of the BMI.
 The ratio of actual BMI to upper limit BMI (currently
defined at BMI 25).
 Individuals can tell, what percentage they deviate
from normal.
 BMI Prime
1. < 0.74 – underweight
2. between 0.74 and 0.99 - optimal weight
3. >/=1.00 overweight

68. Category BMI BMI Prime Weight of a
person with this
BMI(Kg)
Severely
underweight
Less than 16.5 Less than 0.66 Less than 53.5
Underweight 16.5 to 18.5 0.66 to 0.74 53.5 to 60
Normal 18.5 to 25 0.74 to 1 60 to 81
Overweight 25 to 30 1 to 1.2 81 to 97
Obese I 30 to 35 1.2 to 1.4 97 to 113
Obese II 35 to 40 1.4 to 1.6 113 to 130
Severely Obese 40 to 45 1.6 to 1.8 130 to 146
Morbid Obese 45 to 50 1.8 to 2.0 146 to 162
Super Obese 50 to 60 2.0 to 2.4 162 to 194
Hyper Obese Above 60 Above 2.4 Above 194

69. WAIST TO HIP RATIO
 Central or abdominal obesity is associated with
more co morbid conditions.
 So measuring central obesity is of greater
significance
 W/H ratio is taken by a simple measure tape
 in men > 102 cm/90
 in women > 88 cm/80

70. DISEASE RISK (RELATIVE TO NORMAL
WEIGHT AND WAIST CIRCUMFERENCE)
Class Men < 102 Women < 88
cm
Men 102 cm
Women 88 cm
Underweight -- -- --
Normal -- -- --
Overweight increases increases high
Obesity grade I high high Very high
Obesity grade II Very high Very high Very high
Extreme obesity Extremely high Extremely high Extremely high

71. SKIN FOLD THICKNESS
 Harpenders callipers / MRNL callipers
 It is measured at biceps/triceps/illiac and
interscapular.
 Total of all four sites is considered
15-45 mm – 8-22 % of total body fat
46-75 mm – 23-30 % of total body fat
76-150 mm – 31-40 % of total body fat
151-170 mm – 41-45 % of total body fat
Upto 22% it is normal (males)
Upto 30% it is normal (females)

73. BIOMETRIC IMPEDANCE
 Radio frequency current is introduced in body
through electrodes
 Fat has less number of electrolytes
 Water is less conductive

74. CT/MRI
 They can differentiate subcutaneous from visceral
fat and so are important in research purposes.

75. DEXA (DUAL ENERGY
XRAY ABSORPTIOMETRY)

76. AIR DISPLACEMENT PLETHYSMOGRAPHY

77. TOTAL BODY ELECTRICAL CONDUCTIVITY

78. HYDROMETRY (MOST ACCURATE)

79. CLASSIFICATION OF OBESITY (BMI)
 Underweight- BMI < 18.5
 Normal weight- BMI between 18.5 to 24.9
 Overweight- BMI between 25.0 to 29.9
 Obese grade I- BMI between 30.0 to 34.9
 Obese grade II- BMI between 35.0 to 39.0
 Obese grade III ( morbid obese)- BMI ≥ 40

80. CLASSIFICATION OF OBESITY (BMI)
 Starvation
 Underweight
 Normal
 Overweight
 Obese
 Morbidly Obese
Less than 14.9
From 15 to 18.4
From 18.5 to 22.9
From 23 to 27.5
From 27.6 to 40
Greater than 40
It is used in SINGAPORE.
It is to applied in INDIA.

81. CLASSIFICATION OF OBESITY (CLINICAL)
 Stage 0: no apparent obesity-related risk factors
 Stage 1: presence of obesity-related sub-clinical
risk factors, mild physical symptoms.
 Stage 2: presence of established obesity-related
chronic disorders
 Stage 3: established end-organ damage
 Stage 4: severe (end-stage?) disabilities

82. CLASSIFICATION OF OBESITY (FAT)
 82% lean
 18% body fat body mass
 Body fat 25% in men -obese
 Body fat 30% in women – obese
 This method is used in JAPAN.

83. CLASSIFICATION OF OBESITY (SHAPE)
 Apples- Android
It is characterized by central abdominal obesity
It is clinically more important as disease are more
correlated with this abdominal fat
 Pears – Gynecoid
It is characterized by accumulation of fat around hip
and buttocks.

85. CO MORBIDITIES OF OBESITY
 Insulin resistance
 Type II diabetes mellitus
 Reproductive disorders
 Cardiovascular disorders
 Pulmonary disorders
 Gastrointestinal diseases
 Renal diseases
 Cancers
 Bone, joint and cutaneous diseases
 Retinal diseases
 Psychological problems

86. OBESITY AND INSULIN RESISTANCE
 Mainly associated with Intra abdominal fat
 Mainly muscle and adipose are resistant.
 Factors that play a role are
1. Insulin
2. FFA  decreased mitochondria  decrease
action of insulin.
3. Intracellular lipid accumulation
4. Adipokines (resistin) decreases mRNA expression
5. TNF-alpha, IL-6  inflammatory process
6. Reduced activity of Leptin, Adiponectin

87. INSULIN RESISTANCE-COMPLICATIONS
 Muscle – hyperglycemia and DM II
 Kidneys – Salt retention and Hypertension
 Ovaries – Increase testosterone and PCOS
 Heart – Increase plasminogen activator inhibitor (
PAI 1) and ACS
 Cancers – Colon, Prostrate, Breast
 Sympathetic system – Increase Cytokines and
increase Blood Pressure.

88. OBESITY AND DIABETES
 Though patients develop IR not all develop
Diabetes.
 Though it’s a major risk factor for DM.( 85% of type
II DM are Obese)
 If BMI > 35 - 93 times more likely to develop DM.
 There is direct correlation between BMI and DM.

89. OBESITY AND DYSLIPIDAEMIA
 Increase LDL, TG
 Decrease HDL
 All this is because of decrease activity of
Lipoprotein Lipase.
 10% wt gain  12 mg/dl increase in cholesterol.
 With treatment there is improvement in
dyslipidemias

90. OBESITY AND HYPERTENSION
 Increased blood volume
 Increase cardiac output
 Increase sympathetic tone
 Increase Salt sensitivity
 Salt retention by insulin
 Increase angiotensinogen
HYPERTENSION

91. OBESITY AND METABOLIC SYNDROME
Insulin
resistance
obesity dyslipidemia hypertension
DEADLY
QUARTET
METABOLIC
SYNDROME

92. OBESITY AND GASTRO INTESTINAL DISEASES
 Esophagus – GERD
 Stomach – gastroparesis ( DM )
 Gall stones
 NASH
 NAFLD

93. OBESITY AND REPRODUCTIVE DISORDERS
Men
 Plasma Testosterone and SHBG are reduced
 Increase Estrogen
 Gynaecomastia seen
Secondary sexual characters preserved.
Women
 IncreasedAndrogen
 Decrease SHBG
 PCOS
 Uterine cancer (lower body obesity )
 Not only fertility but their chances of IVF success
reduces

94. OBESITY AND ATHEROSCLEROSIS
 Leptin causes ROS production from monocytes
 Low Adiponectin reduces protection from monocyte
adhesion
 TNF alpha, IL6, ICAM1 and VCAM1 affect
endothelium via Transcription Factor KB
 PAI1 increased by TF-KB
 Angiotensinogen increases

95. OBESITY AND CARDIOVASCULAR DISEASE
 Hypertension
 Dyslipidaemias
 Endothelial damage
 Diabetes
 OSA
 W/H ratio may be the best predictor
 BMI > 29…..3 fold rise in MI
 Obesity is responsible for 17% of all CVD
 Angina increases by 1.8 times
 MI increases by 3.2 and 1.5 fold in woman and men
respectively. .
Cardi vascular
complications

96. OBESITY AND LVH
 It is eccentric as well concentric hypertrophy
 Causes
Hypertension ( eccentric )
Increased blood volume  Starling principle
 There is fatty infiltration of myocytes

97. OBESITY AND CARDIOMYOPATHY
 Fat accumulates in cords of cells leadin to a variety
of conduction disturbances.
 All kinds of ARRYTHMIAS
 AF in presence of LVH poorly tolerated.
 QT prolongation in 10% cases.
Fatty infiltration of conducting system.
Hypercapnia
Hypoxia
CAD
Sleep Apnoea

98. OBESITY AND STROKE
 Abdominal Obesity is an independent risk factor
Others include
Hypertension
Dyslipidaemis

99. OBESITY AND PULMONARY DISEASE
 SDB – Sleep Disordered Breathing ( AHI )
 OSAS – Obstructive Sleep Apnoea Syndrome
 OHS – Obesity Hypoventilation Syndrome
 Asthma

100. OSAS – OBSTRUCTIVE SLEEP APNOEA
SYNDROME
 > 30 episodes
 Apnoea > 10 sec (SDB – Sleep Disordered
Breathing )
 Daytime drowsiness
 Snoring at night
 Memory loss
 Mood swings
Cause
REM atonia
Increase soft tissue infiltration around neck
Decreased chest wall compliance
Diaphragmatic displacement in supine

101. OSAS – OBSTRUCTIVE SLEEP APNOEA
SYNDROME
 Complications
1. Pulmonary hypertension
2. RVF
3. HT
4. Stroke
5. Arrythmias (flutter,bradycardia)
6. VT
7. Car accidents

102. OHS – OBESITY HYPOVENTILATION
SYNDROME
 Old name – PICKWICKIAN SYNDROME
 Chronic alveolar hypoventilation in Obese with BMI
> 30 (PaO2 <70 PaCO2 >45 )
 Cause
High work of breathing
Dysfunction of respiratory centre
Repeated nocturnal sleep apnoea

103. OBESITY AND ASTHMA
Cause
Reduced TLC
Reduced RV and FRC
Relation between obesity and asthma is because
1. Common etiologies
2. Co morbidities
3. Adipokines
4. Mechanical factors

104. OBESITY AND RENAL DISEASE
 Increase glomerular remodelling
 Increase kidney weight-increased cellular
proliferation.
 This changes in long term lead to glomerular
sclerosis and DM nephropathy.

105. OBESITY AND CANCERS
 Obesity is the biggest preventable cause of Cancer
after smoking.
 Accounts for 14% of cancer deaths in Men and
20% in women.
Males : Females :
Esophagus
Colon
Rectum
Pancreas
Liver
Prostrate
Gall bladder
Bile ducts
Breasts
Endometrium
Cervix
Ovaries

106. OBESITY AND SKIN DISEASES
 Acanthosis Nigricans:
Thickening of skin folds of neck, elbows,
Dorsal interphalyngeal spaces
Reflects severity of IR
 Friability of skin and varicosities.
 Aggravation of other conditions caused by DM
1. Necrobiosis lipoidica
2. Ulcers
3. Infections

107. OBESITY AND ORTHOPAEDIC DISEASE
 Osteoarthritis
 Hyperuricemia
 Gout
 Accidental injury- decrased mobility, daytime
somnolence

108. OBESITY AND RETINAL DISEASE
 Overweight diabetics are twice more likely to
develop retinopathy than non obese.
 Waist to hip ratio was only second to glycaemic
control in its importance in preventing retinopathy.

109. OBESITY AND PSYCHOLOGICAL PROBLEMS
Are obese people more jolly?
NO
Obesity  psychological problems
Psychological problems  obesity

110. OBESITY AND PSYCHOLOGICAL PROBLEMS
 50% overweight lack self confidence
 Depression
Obesity has more risk of depression in Women
 More physical and sexual abuse
 Lack of attention
 Low education
 Low self esteem

111. MANAGEMENT OF OBESITY
It is a chronic medical condition
Definition of successful treatment:
 Attainment of normal weight
 No treatment induced morbidity
This is rarely achieved in clinical practice.

112. MANAGEMENT OF OBESITY

113. LIFE STYLE MODIFICATION

114. DIET
 Low calorie diet
 Low in saturated fats
 Normal protein intake
 Increased fibers in diet
 Low density foods
 1000 K cal deficit produces 1 kg wt loss per week

115. SELF LIMITING
 No matter what the calorie intake is the constituents
remain in same proportion
 i.e
Carbohydrates 55%
Fat 30%
Protein 15%
 Results in wt loss 2-6 kg over1 year

116. FIXED ENERGY DIET
 Intake is limited by controlling portion sizes, menu
choice and composition
 Minimal self monitoring
 1200 to 1800 kcal
 Lack of compliance to this rigid pattern

117. LOW CALORIE DIET
 800-1000 Kcal
 Applicable to most of the patients
 Fewer restrictions than VLCD.
 Supplementation of vitamins and minerals is
required
 Over a year there is reduction of 6 to 7 kgs.

118. VERY LOW CALORIE DIET
 400 – 600 calorie diet.
 Even below one’s basal metabolic rate
 Used for period of 1 to 2 months under medical
supervision
 45 to 70 % protein
 30 to 50 % carbohydrates
 2g fat
 Supplemented with vitamins, minerals and trace
elements
 Greater wt loss compared to restrictive diets

119. VERY LOW CALORIE DIET
 Complications -fatigue, hair loss, dry skin, dizziness
difficulty concentrating, cholelithiasis, pancreatitis,
gall stones.
 Contraindications – pregnancy, cancer, MI, hepatic
disease, CV Stroke.

120. TOTAL FASTING
 Not recommended
 There is diuresis, natriuresis
 All deficiencies
 Re Feeding Syndrome-severe an potentially fatal
electrolyte, fluid and metabolic abnormalities when
feeding is resumed.

121. LIQUID PROTEIN DIET
 Banned
 Used in 1970’s
 Life threateningArrythmias.

122. HIGH PROTEIN DIETS
High protein
Increase
ketones
diuresis
Wight loss
Increase
purines and
urea
Gout

123. FAT INTAKE
 Decreased fat intake without decreased calories is
of no use
 Because if fat is replaced by carbohydrates there is
rise in triglycerides.
 Instead saturated fats should be replaced by MUFA
or PUFA

124. PHYSICAL ACTIVITY

125.  ScienceDaily (Dec. 12, 2008) — Severely obese
patients who have lost significant amounts of
weight by changing their diet and exercise habits
may be as successful in keeping the weight off
long-term as those individuals who lost weight after
bariatric surgery, according to a new study
published online by the International Journal of
Obesity

126. PHARMACOTHERAPY
 Indications -
1. BMI > 30
2. BMI > 27 with risk factors like HT, DM, CHD,
Sleep Apnoea, Dyslipidemia.

127. PHARMACOTHERAPY
 Phenteramine
 Phenylpropanolamine
 Fenfluramine
 Fen-phen
 Sibutramine
 Orlistat
 Ribonabant
 Metformin
 Olestra
 Leptin

128. PHARMACOTHERAPY
 Tesofensine
 Betahistine
 Amylin
 Melanocortin-4 receptor agonist
 Neuropeptide Y antagonists
 Beta(3) adrenergic agonists
 Glucagon-like peptide-1 agonists.

129. AMPHETAMINE
 Dextro amphetamine was used as anti obesity drug
 Tachycardia, HT, Abuse potential

130. PHENTERAMINE
 Amphetamine like drug
 Act centrally to reduce appetite
 Low addictive potential
 Modest efficacy
 CVS side effects

131. FENFLURAMINE
 Inhibit serotonin uptake
 Modest efficacy as single agent

132. FEN PHEN
 Combination fenfluramine and phentermine
 drugs exerted independent actions on brain satiety
mechanisms
 Primary Pulmonary hypertension increases 20 fold
in this patients.
 Drug was withdrawn in 1997.

133. SIBUTRAMINE
 Originally an anti depressant
 Mechanism of action –
Mono amine reuptake inhibitor ( primarily serotonin
and norepinephrine )
 Site of action - Central nervous system
 Absorption – 77 %
 Protein binding – 94 %

134. SIBUTRAMINE
 Time to peak concentration – 1-2 Hrs.
 Metabolism – Hepatic enzymes, Cytochrome 3A4
to active metabolites M1 and M2
 Excretion – Urine ( 77 % )
 Half Life – M1 – 14 hrs, M2 – 16 hrs

135. SIBUTRAMINE
 Dose – 10 to 15 once daily.
 FDA Approval – for adults and adolescents.
 Side Effects – hypertension ( DBP increases by 2 to
3 mm ) and tachycardia ( 3/ min), sweating,
dizziness and headache.
 Contraindications – coronary artery disease,
cardiac arrythmias, uncontrolled HT
 Effects – 20 % decrease in calorie intake.

136. SIBUTRAMINE
 Advantages
1. It causes sympathetic stimulation and thereby.
prevent decrease in BMR.
2. There is improvement in FBS.
3. Decrease in TG and cholesterol.
4. About 7 % wt loss.

137. ORLISTAT
 Mechanism of action – non systemic reversible
inhibitor of gastric and pancreatic lipases by
forming a covalent bond with serine residue
 Site of action - stomach and intestine
 Absorption – minimal
 Protein binding – > 99 %

138. ORLISTAT
 Time to peak concentration – 8 Hrs.
 Metabolism – In GI Tract to inactive metabolites.
 Excretion – Faeces ( 97 % ). 83 % is unchanged.
 Half Life – 14 – 19 hrs.

139. ORLISTAT
 Dose – 120 mg BD or TID with meals
 FDA Approval – for adults and adolescents as well
as children.
 Side Effects – flatulence, defecation increases, oily
evacuation, rectal leakage, steatorrhoea.
 Contraindications – cholestasis, hypersensitivity,
pregnancy, nursing mothers,

140. ORLISTAT
 Precautions –
1. Patient should take 3 main meals into which
dietary constituents are equally divided.
2. Multivitamins are to be added
3. High fat diet should be avoided as it will lead to
fatty large stools.
 Overdose – it is safe as significant overdoses are
seen without any harmful effects.
 Pellets – pelletized formulations increasing surface
area of the drugs are also available.

141. ORLISTAT
 Advantages –
1. Weight loss observed within 2 weeks of starting
therapy
2. 6 kg weight loss in a year
3. Decrease LDL cholesterol, and raises HDL
cholesterol.
4. Reduces Systolic and Diastolic blood pressure.
5. Reduces waist and hip circumferance
6. Weight regain is also less significant.

142. RIMONABANT
 Mechanism of action – Endocannabinoid (CB1)
receptor blocker.
 Site of action – CNS
 Absorption – not known
 Plasma protein binding – 99.9 %
 Time to peak concentration – 2 hrs

143. RIMONABANT
 Metabolism – hepatic enzymes
 Excretion – fecal via biliary route
 FDA approval – BANNED
 Side effects – depression, anxiety, suicidal
tendencies.

144. METFORMIN
 Decreases appetite and thereby reduces weight
 Since most DM II patients are Obese this is a good
choice in DM II.

145. OLESTRA
 Normal fats consist of a glycerol molecule with
three fatty acid tails attached.
 Olestra is synthesized using a sucrose molecule,
which can support from six to eight fatty acid chains
arranged radially like an octopus
 Too large to move through the intestinal wall and be
absorbed.
 Same taste and mouth feel as fat
 Approval as a food additive upto 35% replacement
of fats in home cooking and 75% in commercial
uses.

146. OLESTRA
 Decline in blood cholesterol levels
 Failed to demonstrate the 15% reduction required
by the FDA to be approved as a treatment
 Side effects-
1. abdominal cramping
2. loose stools.
3. Vitamins A, D, E, and K deficiency
4. anal leakage
5. increase in bowel movement frequency

147. AMYLIN
PRAMLINTIDE (BRAND NAME SYMLIN)
 Part of the endocrine pancreas and contributes to
glycemic control
 Functions as a synergistic partner to insulin
 It is cosecreted from pancreatic beta cells in
response to meals
 Reduction of food intake, slowing of gastric
emptying, inhibition of digestive secretion
 It was recently approved for adult use in patients
with both diabetes mellitus type 1 and diabetes
mellitus type 2
 Insulin and pramlintide, injected separately but both
before a meal,

148. TESOFENSINE
 Tesofensine (TE) is a norepinephrine, dopamine,
and serotonin reuptake inhibitor
 Originally researched for the treatment of
Alzheimer's disease and Parkinson's Disease
 Primarily as an Appetite suppressant
 Positive effects on fat oxidation and resting energy
expenditure
 Weight loss of approximately 4% for >14 weeks
without any diet and lifestyle therapy
 Final stage trials are scheduled to begin in early
2009 in which the 0.5mg dose will be tested.

149. TESOFENSINE
 Dry mouth
 Insomnia
 Tachycardia
 Constipation
 Nausea
 Diarrhoea
 high blood pressure

150. BETAHISTINE
 Blocking the brain's histamine-1 receptor causes
weight gain
 Stimulating the histamine-1 receptor appears to
reduce the craving not only for food in general but
for fatty foods in particular
 Participants lost up to 12 percent of their body
weight
 No side effects
 Not approved by FDA.

151. MELANOCORTIN-4 RECEPTOR AGONIST
 Suppresses food intake when administered to
db/db mice that lack functional leptin receptors
 Peptide 1 (BL3020–1), was selected according to
its selectivity in activating the MC4R, its favorable
transcellular penetration through enterocytes and
its enhanced intestinal metabolic stability
 once daily oral dosing (0.5 mg/kg/day) for 12 days
reduced weight gain.

152. NPY RECEPTOR ANTAGONIST (1229U91 )
 reduced spontaneous food intake
 suppressed water intake
 no abnormal change in general behavior
 suppressed spontaneous food intake in lean rats
also
 doses of 10 and 30 µg

153. BETA(3) ADRENERGICAGONISTS
1. Amibegron
2. Solabegron
 Enhancement of lipolysis in adipose tissue

154. GLUCAGON-LIKE PEPTIDE-1 AGONISTS (BOC5)
 (GLP)-1 is produced by the intestine
 stimulates insulin secretion
 Boc5 one of the first non-peptidic agonists at
glucagon-like peptide-1
 dose-dependently inhibited food intake

155. BARIATRIC SURGICAL TECHNIQUES
 Divided into two groups
1. Malabsorptive procedures - Induce decreased
absorption of nutrients by shortening the functional
length of the small intestine
2. Restrictive procedures - Reduce the storage
capacity of the stomach and as a result early
satiety arises, leading to a decreased caloric
intake

156. BARIATRIC SURGICAL TECHNIQUES
 Indications -
1. BMI greater than 40, or 100 pounds overweight
2. BMI 35-39.9 and a life-threatening condition, such
as heart disease or diabetes.
3. BMI 35-39.9 and severe physical limitations that
affect employment, mobility, and family life

157. MALABSORPTIVE PROCEDURES
 Jejunoileal bypass
 Biliopancreatic diversion
 Biliopancreatic diversion with duodenal switch

158. THE JEJUNOILEAL BYPASS
 One of the first bariatric operations
 It is associated with substantial long-term
complications -
1. liver failure
2. Malnutrition
3. electrolyte imbalances
4. vitamin deficiencies
5. renal (oxalate) stones
6. Death
 This procedure is therefore no longer performed

159. BILIOPANCREATIC DIVERSION
 A partial gastrectomy is performed, creating a 100–
150 ml gastric pouch
 gastro-jejunostomy or gastro-ileostomy
 long (food) limb is anastomosed to the
biliopancreatic (bile,pancreatic juice) limb

160. BILIOPANCREATIC DIVERSION WITH DUODENAL
SWITCH
 A pylorus-sparing sleeve gastrectomy with
duodeno-ileostomy is performed
 less cases of dumping and marginal ulcers than a
classical biliopancreatic diversion

161. RESTRICTIVE PROCEDURES
 Vertical banded gastroplasty
 Laparoscopic adjustable gastric band

162. RESTRICTIVE PROCEDURES
 simpler to perform
 less procedural complications
 Represent the current most frequently performed
restrictive procedures
 Two approaches –
1. Open
2. Laparoscopic

163. COMPLICATIONS
 Vomiting
 Leak into the abdomen
 Slipping or wearing away of the band
 Enlargement of the pouch
 Reflux esophagitis
 Vitamin deficiencies
 Wound infection
 Bleeding
 Abdominal hernia
 Gallstones
 Heart and lung problems
 Phlebitis, embolism
 Complications of general anesthesia
 Death, occurs in less than 1% of patients

164. COMBINED PROCEDURE
 Roux-en-Y gastric bypass
1. It is (at least in the United States) the most
frequently performed bariatric procedure
2. Both restrictive and malabsorptive aspects
3. A (restrictive) gastric pouch is created and
separated from the remainder of the stomach.
4. The continuity is then restored by a Roux-Y-limb,
which is connected to the jejunum

165. SUCCESS OF BARIATRIC PROCEDURES
 20–40 kg of weight loss
 10–15 kg/m2 reduction inBMI

166. THANK YOU