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
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 :
1. Arcuate Nuclei-
site for action of leptin and insulin.
primary
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.
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.
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.
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
28.
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
32.
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
34.
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.
36.
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, brachydactyly
or polydactyly)
Retinal dystrophy or pigmentary retinopathy
Hypogonadism or hypogenitalism (limited to male
patients)
Structural abnormalities of the kidney or functional
renal impairment.
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.
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
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.
45.
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
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
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
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.
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)
72.
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.
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.
84.
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
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
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
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.
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
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.
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
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
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.
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
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
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
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