1. OBESITY

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

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 : Arcuate Nuclei- primary site for action of leptin and insulin. Para Ventricular Nuclei- AMP kinase mediated appetite regulation Dorsomedial Hypothalamic Nuclei- destruction leads to hyperphagia and obesity

8. Neurohumoral 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: counteracts the effects of neuropeptide Y (a potent feeding stimulant secreted by cells in the gut and in the hypothalamus); counteracts the effects of anandamide (another potent feeding stimulant that binds to the same receptors as THC, the active ingredient of marijuana) promotes the synthesis of α-MSH, an appetite suppressant; RESULT- inhibition of food intake.

10. Leptin Increase leptin Increased POMC PC 1 Increased alpha-MSH Increased Melanocortin receptor signal Decreased Appetite

14. Leptin

15. 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

16. 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.

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

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

19. Pancreatic Hormones Plasma PP are inversely co related with adipocity Patients with PraderWilli have decrease amount of PP

20. Gut Hormones PYY- Secreted from L cells of GI tract Reduces food intake Ghrelin- mainly secreted from stomach A potent Orexigenic Cholecystokinin Mainly secreted in duodenum Decreasing meal size and duration both.

21. Adipose tissue Tnf alpha IL 6 PAI 1 Impaired signal transduction of insulin Decrease NO mediated vaso dilatation Decrease GLUT 4 atherosclerosis INSULIN RESISTANCE Impaired insulin signalling

22. 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.

23. 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

24. Etiology of obesity- adoption studies Strong relationship between the BMI of adoptees and biological parents.

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

32. PraderWilli 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, hypogonadotropichypogonadism, and small hands and feet Hyperphagia is a dominant feature in PWS

34. PraderWilli Syndrome diminished growth reduced muscle mass (lean body mass) increased fat mass - body composition hypogonadotrophichypogonadism Fasting plasma ghrelin levels are 4.5-fold higher in PWS subjects

36. 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.

38. 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

39. BardetBiedl 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.

40. 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. Increase leptin leptin receptor Increased POMC Decreased AgRP PC 1 Increased alpha-MSH Increased Melanocortin receptor signal Decreased Appetite

42. 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 Hypogonadotropichypogonadism

43. Congenital leptin deficiency

45. 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.

47. 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. Increase leptin leptin receptor Increased POMC Decreased AgRP PC 1 Increased alpha-MSH Increased Melanocortin receptor signal Decreased Appetite

49. 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

51. Increase leptin leptin receptor Increased POMC Decreased AgRP PC 1 Increased alpha-MSH Increased Melanocortin receptor signal Decreased Appetite

52. ProhormoneConvertase 1 deficiency childhood obesity abnormal glucose homeostasis very low plasma insulin elevated levels of pro insulin hypogonadotropichypogonadism hypocortisolaemia elevated levels of POMC

53. Increase leptin leptin receptor Increased POMC Decreased AgRP PC 1 Increased alpha-MSH Increased Melanocortin receptor signal Decreased Appetite

54. 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

56. Increase leptin leptin receptor Increased POMC Decreased AgRP PC 1 Increased alpha-MSH Increased Melanocortin receptor signal Decreased Appetite

57. AgRP deficiency AgRP antagonizes alpha MSH action So deficiency leads to overexpression of MC4R receptor.

58. Other molecular defects TUB gene – late onset Obesity FAT gene – obesity by disruption of neuropeptides.

59. Endocrinal Abnormalities-Cushing syndrome Increased cortisol production Hypertension Glucose intolerance Cushingoidfacies

60. Endocrinal Abnormalities-Hypothyroidism Uncommon cause of obesity Much of weight gain is due to Myxedema Ruled out by serum TSH.

61. Endocrinal Abnormalities-Insulinoma In order to avoid hypoglycemia patients often eat more leading to weight gain. High insulin promote fat genesis.

62. Endocrinal Abnormalities-Syndrome X Central obesity Glucose intolerance Dyslipidemia hypertension

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

64. Craniopharyngioma-other disorders of Hypothalamus Tumours inflammation trauma GH decreases but Somatomedin is normal.

65. 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.

66. 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)

67. 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

68. 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 < 0.74 – underweight between 0.74 and 0.99 - optimal weight >/=1.00 overweight

70. 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

71. Disease Risk (Relative to Normal Weight and Waist Circumference)

72. Skin fold thickness Harpenderscallipers / 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)

74. Biometric Impedance Radio frequency current is introduced in body through electrodes Fat has less number of electrolytes Water is less conductive

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

76. DEXA (Dual Energy XrayAbsorptiometry)

77. Air displacement Plethysmography

78. Total body electrical conductivity

79. Hydrometry (most accurate)

80. 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

81. 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.

82. 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

83. 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.

84. 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.

86. 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

87. Obesity and Insulin Resistance Mainly associated with Intra abdominal fat Mainly muscle and adipose are resistant. Factors that play a role are Insulin FFA  decreased mitochondria  decrease action of insulin. Intracellular lipid accumulation Adipokines (resistin) decreases mRNA expression TNF-alpha, IL-6  inflammatory process Reduced activity of Leptin, Adiponectin

88. 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.

89. 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.

90. 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

91. Obesity and hypertension Increased blood volume Increase cardiac output Increase sympathetic tone Increase Salt sensitivity Salt retention by insulin Increase angiotensinogen HYPERTENSION

92. Obesity and metabolic Syndrome Insulin resistance obesity dyslipidemia hypertension DEADLY QUARTET METABOLIC SYNDROME

93. Obesity and Gastro Intestinal diseases Esophagus – GERD Stomach – gastroparesis ( DM ) Gall stones NASH NAFLD

94. 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

95. 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

96. 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

97. Obesity and LVH It is eccentric as well concentric hypertrophy Causes Hypertension ( eccentric ) Increased blood volume  Starling principle There is fatty infiltration of myocytes

98. 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

99. Obesity and Stroke Abdominal Obesity is an independent risk factor Others include Hypertension Dyslipidaemis

100. Obesity and Pulmonary disease SDB – Sleep Disordered Breathing ( AHI ) OSAS – Obstructive Sleep Apnoea Syndrome OHS – Obesity Hypoventilation Syndrome Asthma

101. 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

102. OSAS – Obstructive Sleep Apnoea Syndrome Complications Pulmonary hypertension RVF HT Stroke Arrythmias (flutter,bradycardia) VT Car accidents

103. 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

104. Obesity and Asthma Cause Reduced TLC Reduced RV and FRC Relation between obesity and asthma is because Common etiologies Co morbidities Adipokines Mechanical factors

105. Obesity and Renal disease Increase glomerularremodelling Increase kidney weight-increased cellular proliferation. This changes in long term lead to glomerular sclerosis and DM nephropathy.

106. 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.

107. Obesity and Skin diseases AcanthosisNigricans: 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 Necrobiosislipoidica Ulcers Infections

108. Obesity and Orthopaedic Disease Osteoarthritis Hyperuricemia Gout Accidental injury- decrased mobility, daytime somnolence

109. 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.

110. Obesity and Psychological problems Are obese people more jolly? NO Obesity  psychological problems Psychological problems  obesity

111. 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

112. 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.

113. Management of Obesity

114. Life Style Modification

115. 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

116. 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

117. 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

118. 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.

119. 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. 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.

121. 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. Liquid Protein Diet Banned Used in 1970’s Life threatening Arrythmias.

123. High Protein Diets High protein Increase ketones Increase purines and urea diuresis Gout Wight loss

124. 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. Physical Activity

126. 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

127. Pharmacotherapy Indications - BMI > 30 BMI > 27 with risk factors like HT, DM, CHD, Sleep Apnoea, Dyslipidemia.

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

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

130. Amphetamine Dextro amphetamine was used as anti obesity drug Tachycardia, HT, Abuse potential

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

132. Fenfluramine Inhibit serotonin uptake Modest efficacy as single agent

133. 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.

134. 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 %

135. 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

136. 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.

137. Sibutramine Advantages It causes sympathetic stimulation and thereby. prevent decrease in BMR. There is improvement in FBS. Decrease in TG and cholesterol. About 7 % wt loss.

138. 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 %

139. 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.

140. 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,

141. Orlistat Precautions – Patient should take 3 main meals into which dietary constituents are equally divided. Multivitamins are to be added 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.

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

143. 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

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

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

146. 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.

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

148. 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,

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

151. 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.

152. 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.

153. 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 and30 µg

154. Beta(3) adrenergic agonists Amibegron Solabegron Enhancement of lipolysis in adipose tissue

155. 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

156. Bariatric surgical techniques Divided into two groups Malabsorptiveprocedures - Induce decreased absorption of nutrientsby shortening the functional length of the small intestine Restrictive procedures - Reduce the storage capacity of the stomachand as a result early satiety arises, leading to a decreasedcaloric intake

157. Bariatric surgical techniques Indications - BMI greater than 40, or 100 pounds overweight BMI 35-39.9 and a life-threatening condition, such as heart disease or diabetes. BMI 35-39.9 and severe physical limitations that affect employment, mobility, and family life

158. Malabsorptiveprocedures Jejunoileal bypass Biliopancreatic diversion Biliopancreatic diversion with duodenal switch

159. The jejunoileal bypass One of the first bariatric operations It is associated withsubstantial long-term complications - liver failure Malnutrition electrolyte imbalances vitamin deficiencies renal (oxalate) stones Death This procedure is thereforeno longer performed

160. Biliopancreatic diversion A partial gastrectomy is performed, creating a 100–150ml gastric pouch gastro-jejunostomyor gastro-ileostomy long (food) limb is anastomosed tothe biliopancreatic (bile,pancreaticjuice) limb

161. Biliopancreatic diversion with duodenal switch A pylorus-sparing sleeve gastrectomy with duodeno-ileostomyis performed less cases of dumpingand marginal ulcers than a classical biliopancreatic diversion

162. Restrictive procedures Vertical banded gastroplasty Laparoscopic adjustable gastric band

163. Restrictive procedures simpler to perform less procedural complications Represent the currentmost frequently performed restrictive procedures Two approaches – Open Laparoscopic

164. 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

165. Combined procedure Roux-en-Y gastric bypass It is (atleast in the United States) the most frequently performed bariatricprocedure Both restrictive and malabsorptive aspects A (restrictive) gastric pouch is created andseparated from the remainder of the stomach. The continuityis then restored by a Roux-Y-limb, which is connected to thejejunum

166. Success of Bariatric Procedures 20–40 kg of weight loss 10–15kg/m2 reduction in BMI

167. THANK YOU