OBESITY

DEFINITION

Latin word “OBESUS” meaning stout, fat, plump.

It is defined as a state of excess adipose tissue.

BMI ≥ 30

OBESITY VS OVERWEIGHT

Overweight – Fat Fluid Muscle mass Bone Tumours

Obesity – Fat ( adipose tissue )

EPIDEMIOLOGY

>1.6 billion overweight of which 400 million are obese

Women > men More common even in poor

India 12.1 14 16 15States Males (%) Males rank Females (%) Females rank

States Males (%) Males rank Females (%) Females rank

Punjab 30.3 1 37.5 1Kerala 24.3 2 34 2Goa 20.8 3 27 3Tamil Nadu 19.8 4 24.4 4Andhra Pradesh 17.6 5 22.7 10Sikkim 17.3 6 21 8Mizoram 16.9 7 20.3 17

Himachal Pradesh

16 8 19.5 12

Maharashtra 15.9 9 18.1 13Gujarat 15.4 10 17.7 7Haryana 14.4 11 17.6 6Karnataka 14 12 17.3 9Manipur 13.4 13 17.1 11Uttarakhand 11.4 15 14.8 14

REGULATION OF APPETITE

Appetite – lateral hypothalamus Satiety – ventromedial hypothalamus

Destruction of LHA leads to starvation and death.

Destruction of VMA leads to obesity.

OTHER CENTRES IN REGULATION OF APPETITE :

1. Arcuate Nuclei- primary 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

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

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.

LEPTINIncrease leptin

Increased Melanocortin receptor signal

Increased POMC

Increased alpha-MSH

Decreased Appetite

PC 1

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.

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.

LEPTIN

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

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.

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.

VISFATIN

Produced by visceral fat Increase in response to fatty diet Role in adipose differentiation

PANCREATIC HORMONES

Plasma PP are inversely co related with

adipocity

Patients with Prader Willi have decrease amount of PP

GUT HORMONES

PYY- 1. Secreted from L cells of GI tract 2. Reduces food intake

Ghrelin-1. mainly secreted from stomach2. A potent Orexigenic

Cholecystokinin1. Mainly secreted in duodenum 2. Decreasing meal size and duration both.

Adipose tissue

Tnf alphaIL 6 PAI 1

Decrease GLUT 4

Impaired signal transduction of

insulin

atherosclerosis

Impaired insulin signalling

Decrease NO mediated

vaso dilatation

INSULIN RESISTANCE

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.

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

ETIOLOGY OF OBESITY- ADOPTION STUDIES

Strong relationship between the BMI of adoptees and biological parents.

PLEIOTROPIC OBESITY SYNDROMES

Autosomal dominant

Ulnar Mammary Syndrome: 12q24

Other features- Ulnar defects, delayed puberty, hypoplastic nipples. 

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 

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

PLEIOTROPIC OBESITY SYNDROMES

X linked

• Borjeson-Forssman-Lehmann syndrome : Xq26

Other features- Mental retardation, hypogonadism, large ears 

• Mehmo syndrome : Xp22Other features- Mental retardation, epilepsy,

hypogonadism, microcephaly 

PLEIOTROPIC OBESITY SYNDROMES

X linked

• Simpson-Golabi-Behmel - type 2 : Xp22 Other features- Craniofacial defects, skeletal

and visceral abnormalities 

• Wilson-Turner syndrome : Xp21Other features- Mental retardation, tapering

fingers, gynaecomastia 

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

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

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.

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

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.

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.

Increase leptin

Increased Melanocortin receptor signal

Increased POMC

Increased alpha-MSH

Decreased Appetite

PC 1

leptin receptor

Decreased AgRP

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

CONGENITAL LEPTIN DEFICIENCY

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.

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

Increase leptin

Increased Melanocortin receptor signal

Increased POMC

Increased alpha-MSH

Decreased Appetite

PC 1

leptin receptor

Decreased AgRP

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

Increase leptin

Increased Melanocortin receptor signal

Increased POMC

Increased alpha-MSH

Decreased Appetite

PC 1

leptin receptor

Decreased AgRP

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

Increase leptin

Increased Melanocortin receptor signal

Increased POMC

Increased alpha-MSH

Decreased Appetite

PC 1

leptin receptor

Decreased AgRP

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

Increase leptin

Increased Melanocortin receptor signal

Increased POMC

Increased alpha-MSH

Decreased Appetite

PC 1

leptin receptor

Decreased AgRP

AGRP DEFICIENCY

AgRP antagonizes alpha MSH action So deficiency leads to overexpression of

MC4R receptor.

OTHER MOLECULAR DEFECTS

TUB gene – late onset Obesity FAT gene – obesity by disruption of

neuropeptides.

ENDOCRINAL ABNORMALITIES-CUSHING SYNDROME

Increased cortisol production Hypertension Glucose intolerance Cushingoid facies

ENDOCRINAL ABNORMALITIES-HYPOTHYROIDISM

Uncommon cause of obesity Much of weight gain is due to Myxedema Ruled out by serum TSH.

ENDOCRINAL ABNORMALITIES-INSULINOMA

In order to avoid hypoglycemia patients often eat more leading to weight gain.

High insulin promote fat genesis.

ENDOCRINAL ABNORMALITIES-SYNDROME X

Central obesity Glucose intolerance Dyslipidemia hypertension

ENDOCRINAL ABNORMALITIES-PCOD

2 out 3 criteria for diagnosis1) 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.

CRANIOPHARYNGIOMA-OTHER DISORDERS OF HYPOTHALAMUS

Tumours inflammation trauma GH decreases but Somatomedin is normal.

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.

MEASUREMENT OF OBESITY

BMI Waist hip ratio Skin fold thickness Biometric impedance Ultrasound DEXA (Dual Energy Xray Absorptiometry CT / MRI Air displacement Plethysmography Total body electrical conductivity Hydrometry (most accurate)

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

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 Prime1. < 0.74 – underweight2. between 0.74 and 0.99 - optimal weight3. >/=1.00 overweight

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

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

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

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 fat46-75 mm – 23-30 % of total body fat76-150 mm – 31-40 % of total body fat151-170 mm – 41-45 % of total body fat

Upto 22% it is normal (males)Upto 30% it is normal (females)

BIOMETRIC IMPEDANCE

Radio frequency current is introduced in body through electrodes

Fat has less number of electrolytes Water is less conductive

CT/MRI

They can differentiate subcutaneous from visceral fat and so are important in research purposes.

DEXA (DUAL ENERGY XRAY ABSORPTIOMETRY)

AIR DISPLACEMENT PLETHYSMOGRAPHY

TOTAL BODY ELECTRICAL CONDUCTIVITY

HYDROMETRY (MOST ACCURATE)

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

CLASSIFICATION OF OBESITY (BMI)

Starvation Less than 14.9 Underweight From 15 to 18.4 Normal From 18.5 to 22.9 Overweight From 23 to 27.5 Obese From 27.6 to 40 Morbidly Obese Greater than 40

It is used in SINGAPORE.It is to applied in INDIA.

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

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.

CLASSIFICATION OF OBESITY (SHAPE)

Apples- Android It is characterized by central abdominal obesityIt is clinically more important as disease are

more correlated with this abdominal fat

Pears – GynecoidIt is characterized by accumulation of fat

around hip and buttocks.

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

OBESITY AND INSULIN RESISTANCE

Mainly associated with Intra abdominal fat Mainly muscle and adipose are resistant. Factors that play a role are1. Insulin 2. FFA decreased mitochondria decrease

action of insulin.3. Intracellular lipid accumulation4. Adipokines (resistin) decreases mRNA

expression5. TNF-alpha, IL-6 inflammatory process6. Reduced activity of Leptin, Adiponectin

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.

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.

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

OBESITY AND HYPERTENSION

Increased blood volume Increase cardiac output Increase sympathetic tone Increase Salt sensitivity Salt retention by insulin Increase angiotensinogen

HYPERTENSION

OBESITY AND METABOLIC SYNDROMEInsulin

resistance

obesity

dyslipidemia

hypertension

DEADLY QUARTET

METABOLIC SYNDROME

OBESITY AND GASTRO INTESTINAL DISEASES

Esophagus – GERD Stomach – gastroparesis ( DM ) Gall stones NASH NAFLD

OBESITY AND REPRODUCTIVE DISORDERS

Men Plasma Testosterone and SHBG are reduced Increase Estrogen Gynaecomastia seen Secondary sexual characters preserved.Women Increased Androgen Decrease SHBG PCOS Uterine cancer (lower body obesity ) Not only fertility but their chances of IVF

success reduces

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

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

OBESITY AND LVH

It is eccentric as well concentric hypertrophy CausesHypertension ( eccentric )Increased blood volume Starling principle There is fatty infiltration of myocytes

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.HypercapniaHypoxiaCADSleep Apnoea

OBESITY AND STROKE

Abdominal Obesity is an independent risk factor

Others includeHypertensionDyslipidaemis

OBESITY AND PULMONARY DISEASE

SDB – Sleep Disordered Breathing ( AHI ) OSAS – Obstructive Sleep Apnoea Syndrome OHS – Obesity Hypoventilation Syndrome Asthma

OSAS – OBSTRUCTIVE SLEEP APNOEA SYNDROME

> 30 episodes Apnoea > 10 sec (SDB – Sleep Disordered

Breathing ) Daytime drowsiness Snoring at night Memory loss Mood swings CauseREM atoniaIncrease soft tissue infiltration around neckDecreased chest wall complianceDiaphragmatic displacement in supine

OSAS – OBSTRUCTIVE SLEEP APNOEA SYNDROME

Complications1. Pulmonary hypertension2. RVF3. HT4. Stroke5. Arrythmias (flutter,bradycardia)6. VT7. Car accidents

OHS – OBESITY HYPOVENTILATION SYNDROME

Old name – PICKWICKIAN SYNDROME Chronic alveolar hypoventilation in Obese

with BMI > 30 (PaO2 <70 PaCO2 >45 ) CauseHigh work of breathingDysfunction of respiratory centreRepeated nocturnal sleep apnoea

OBESITY AND ASTHMA

CauseReduced TLCReduced RV and FRCRelation between obesity and asthma is

because1. Common etiologies2. Co morbidities3. Adipokines4. Mechanical factors

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.

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 :

EsophagusColonRectumPancreasLiverProstrate

Females :

Gall bladderBile ductsBreasts EndometriumCervixOvaries

OBESITY AND SKIN DISEASES

Acanthosis Nigricans:Thickening of skin folds of neck, elbows,Dorsal interphalyngeal spacesReflects severity of IR

Friability of skin and varicosities.

Aggravation of other conditions caused by DM1. Necrobiosis lipoidica2. Ulcers3. Infections

OBESITY AND ORTHOPAEDIC DISEASE

Osteoarthritis Hyperuricemia Gout Accidental injury- decrased mobility, daytime

somnolence

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.

OBESITY AND PSYCHOLOGICAL PROBLEMS

Are obese people more jolly?

NOObesity psychological problemsPsychological problems obesity

OBESITY AND PSYCHOLOGICAL PROBLEMS

50% overweight lack self confidence DepressionObesity has more risk of depression in Women More physical and sexual abuse Lack of attention Low education Low self esteem

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.

MANAGEMENT OF OBESITY

LIFE STYLE MODIFICATION

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

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

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

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.

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

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.

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.

LIQUID PROTEIN DIET

Banned Used in 1970’s Life threatening Arrythmias.

HIGH PROTEIN DIETS

High protein

Increase ketones

diuresis

Wight loss

Increase purines and

urea

Gout

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

PHYSICAL ACTIVITY

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

PHARMACOTHERAPY

Indications -

1. BMI > 302. BMI > 27 with risk factors like HT, DM, CHD,

Sleep Apnoea, Dyslipidemia.

PHARMACOTHERAPY

Phenteramine Phenylpropanolamine Fenfluramine Fen-phen Sibutramine Orlistat Ribonabant Metformin Olestra Leptin

PHARMACOTHERAPY

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

AMPHETAMINE

Dextro amphetamine was used as anti obesity drug

Tachycardia, HT, Abuse potential

PHENTERAMINE

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

FENFLURAMINE

Inhibit serotonin uptake Modest efficacy as single agent

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.

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 %

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

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.

SIBUTRAMINE

Advantages1. 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.

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 %

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.

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,

ORLISTAT

Precautions – 1. Patient should take 3 main meals into which

dietary constituents are equally divided.2. Multivitamins are to be added3. 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.

ORLISTAT

Advantages – 1. Weight loss observed within 2 weeks of

starting therapy2. 6 kg weight loss in a year3. Decrease LDL cholesterol, and raises HDL

cholesterol.4. Reduces Systolic and Diastolic blood

pressure.5. Reduces waist and hip circumferance6. Weight regain is also less significant.

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

RIMONABANT

Metabolism – hepatic enzymes

Excretion – fecal via biliary route

FDA approval – BANNED

Side effects – depression, anxiety, suicidal tendencies.

METFORMIN

Decreases appetite and thereby reduces weight

Since most DM II patients are Obese this is a good choice in DM II.

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.

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 cramping2. loose stools.3. Vitamins A, D, E, and K deficiency4. anal leakage5. increase in bowel movement frequency

AMYLINPRAMLINTIDE (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,

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.

TESOFENSINE

Dry mouth Insomnia Tachycardia Constipation Nausea Diarrhoea high blood pressure

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.

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.

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

BETA(3) ADRENERGIC AGONISTS

1. Amibegron2. Solabegron

Enhancement of lipolysis in adipose tissue

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

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

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

MALABSORPTIVE PROCEDURES

Jejunoileal bypass Biliopancreatic diversion Biliopancreatic diversion with duodenal

switch

THE JEJUNOILEAL BYPASS

One of the first bariatric operations It is associated with substantial long-term

complications -1. liver failure2. Malnutrition3. electrolyte imbalances4. vitamin deficiencies5. renal (oxalate) stones6. Death

This procedure is therefore no longer performed

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

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

RESTRICTIVE PROCEDURES

Vertical banded gastroplasty Laparoscopic adjustable gastric band

RESTRICTIVE PROCEDURES

simpler to perform less procedural complications

Represent the current most frequently performed restrictive procedures

Two approaches –1. Open2. Laparoscopic

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

COMBINED PROCEDURE

Roux-en-Y gastric bypass1. It is (at least in the United States) the most

frequently performed bariatric procedure2. Both restrictive and malabsorptive aspects3. 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

SUCCESS OF BARIATRIC PROCEDURES

20–40 kg of weight loss 10–15 kg/m2 reduction in BMI

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