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# Obesity

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### Obesity

1. 1. 7 July 2011, Shridhan A Patil, RCC Trivandrum
2. 2.
3. 3.  Definition : Obesity is a state of excess adipose tissue mass. (Harrison’s :17th ) Obesity is a disease of caloric imbalance that results from an excess intake of calories above their consumption by the body. (Robbins : 8th) The WHO definition is: a BMI greater than or equal to 25 is overweight a BMI greater than or equal to 30 is obesity.
4. 4. BMI/Quetlet index Classification of weight status NOT by mere weight Muscularity & height affect weight So, BMI or Quetlet index used to classify Body Mass Index (BMI)  Most widely used  BMI= Weight(kg) Height(mtr)2
5. 5. WHO Classification BMI Classification <18.5 Underweight  18.5-24.9 Normal weight  25-29.9 Overweight  30-34.9 Obesity Class I  35-39.9 Obesity Class II  40-49.9 Obesity Class III  50 and above Super Obesity
6. 6.  Values are age independent & same for both sexes. At similar BMI, fat content in women > men BMI 30 is threshold for obesity. BMI 25 - 30 medically significant & requires intervention• At a given BMI, women, on average, have more body fat.• Morbidity and mortality increase with BMI similarly for men and women• Risk at a given BMI can vary between populations.
7. 7. Other Indices  Broca’s index = Height ( cms ) – 100  Corpulance index = Actual weight / Desirable weight  Ponderal index = Height ( cms ) Cube root of body weight ( kg )  Lorentz’s formula Height ( cms ) – 100 - Height ( cms ) – 150 2(women) or 4(men)
8. 8. Other methods  Waist hip ratio - >0.9 for women - > 1 for men  Anthropometry ( skin fold thickness )  Harpenden skin calliper  < 40 mm in males, < 50 mm in females  Densitometry ( under water weighing )  CT Scan, MRI, Electric impedance
9. 9. Android=Abdominal=Central=Apple shapedGynecoid=Peripheral=Pearshaped
10. 10. “Super obese" maleA "super obese" male with a BMI of 47 kg/m2: weight 146 kg (322 lb), height 177 cm (5 ft 10 in)
11. 11. Adipocyte Hypertrophy and/or Hyperplasia
12. 12.  Endocrine Drugs Smoking cessation
13. 13. What causes obesity? Inactive advertising neighborhood
14. 14. Energy balance 3 components1. Afferent /peripheral system - Generates signals from various sites - Composed of leptin , adiponectin - by fatcells, ghrelin from stomach, peptide YY (PYY) fromileum, colon, insulin from pancreas
15. 15.  2.Arcuate nucleus in hypothalamus -Processes & integrates neurohumoral peripheral signals -Generates efferent signals -Composed of 2 subsets of first order neurons 1.POMC (pro-opiomelanocortin) & CART (cocaine and amphetamine-regulated transcripts) neurons 2.Neuropeptide Y & AgRP (agouti-related peptide) These first order neurons communicate with second order neurons
16. 16.  3. Efferent system Carries signals from second order neurons of hypothalamus to control food intake and energy expenditure
17. 17. Peripheral Signals
18. 18.  Produced by adipocytes Leptin Leptin Product of „ob‟ gene Provides signal for “energy sufficiency”. Abundant fat  Leptin - + POMC/CART secretion NPY/AgRP neurons Regulated by insulin neurons stimulated glucose metabolism Stimulates Produce Anorexic thermogenesis, activity, ene orexinergic neuropeptides- rgy expenditure neuropeptides (MSH)
19. 19.  MC4R ( Melanocortin receptor 4) mutations- more frequent, cause of 5% massive obesity No satiety(anorexinergic) signal generated Behave as if undernourished Haplo-insufficiency of brain-derived neurotrophic factor (BDNF) – component of MC4R downstream signaling in hypothalamus BDNF - A/w obesity in WAGR syndrome
20. 20. Adiponectin Produced mainly by adipocytes AdipoR1, AdipoR2 in Low levels in obesity skeletal Stimulates fatty acid oxidation muscle, liver, brain “Fat-burning molecule” + cAMP activated “Guardian angel against protein kinase obesity” ↓ fatty acid influx in liver, liver Inactivates acetyl glucose production coenzyme A ↓ Protects against Metabolic carboxylase (Key enzyme in Fatty syndrome acid synthesis)
21. 21.  Produces TNF, IL-6, IL-1, IL-18, Chemokine, Steroids Chronic sub-clinical inflammatory state (^ CRP) ?Link between lipid metabolism, nutrition, inflammationWHY is it HARD to maintain the weight loss for those wholose after dietary restriction?- Constant number of adipocytes- -Higher no. in obese
22. 22. ..
23. 23.  Short term meal initiators and terminatoprs Ghrelin, PYY, Pancreatic polypeptide, Isulin, Amylin Ghrelin(stomach,arcuate nucleus)- only orexenergic gut hormone Most likely stimulates NPY/AgRP neurons PYY ( ileum, colon) A/w hyperphagia , obesity in Prader-Willi syndrome Amylin(pancreatic ß cells), PYY – both stimulate POMC/CART neurons
24. 24. recognized that :“sudden death ismorecommon in thosewho are naturallyfat than in lean.”
25. 25.  Insulin resistance & Type 2 DM – 80 % Type 2 DM are obese Circulating peptides – TNFα, IL6, RBP6, Adiponectin, Resistin have altered expression & modify the insulin action
26. 26. Cardiovascular system - Obesity  Independent risk factor for CAD, CHF Insulin Resistance  Waist – Hip ratio best predictor  Abdominal obesity ↑ Insulin associated with atherogenic lipid profile ↑ FFA  Hypertension ↑ Triglyceride
27. 27. ↑ Adipose tissue ↑ Leptin Hypothalamus- ↑MSH, ↑AgRP, ↓NPY Increased SNS activity Hypertension
28. 28. Syndrome X or Metabolic syndrome  Abdominal obesity  Insulin resistance  Hypertriglyceridemia  Low serum HDL  ↑ risk of CAD  Seen more in Indians, probably due to low levels of adiponectin
29. 29.  Male  Hypogonadism  ↓ Plasma testosterone & sex hormone binding globulin  Estrogen levels ↑  Masculization, libido, potency, spermatogenesis preserved Females –  Menstrual irregularities, oligomenorrhea  ↑ androgen production, ↓sex hormone binding globulin  PCOD – anovulation, obesity, hirsutism
30. 30.  Apnoeic pauses during sleep Hypersomnolence at both day & night Polycythemia Eventually right sided heart falure
31. 31.  Gall stones, Pancreatitis, Abdominal hernia, NAFLD Gall stones  ↑ cholesterol Enhanced billiary excretion of cholesterol  Super saturated bile  Cholelithiasis  In 50 % above ideal body wt. – 6 fold ↑ in symptomatic gall stones
32. 32.  Strongly associated with Obesity, Dyslipidemia, Type 2 DM Presents like – Steatosis & Steatohepatitis 10 – 20 % develop in to Cirrhosis
33. 33.  Stroke  ↑ Blood pressure  Type 2 DM  Elevated cholesterol levels Depression –  Sleep disturbances
34. 34. Bones, Joints, Cutaneous disorders  Osteoarthritis –  Trauma & joint malalignment,  Gout :- ↑ Prevalence  Skin –  Acanthosis nigrans,  Friability of skin, enhancing the risk of fungal & yeast infection
35. 35.  How they are related?  Both sexes affected equally with high mortality rate  In males – Ca. esophagus, colon, rectum, pancreas, liver & prostate  In females – Ca. gall bladder, bile duct, breast, endometrium, cervix, ovaries
36. 36.  Cushing‟s Syndrome –  ↑ cortisol levels  Promotes deposition of adipose tissue in peculiar distribution  Upper face – Moon Facies  Inter scapular area – Buffelow Hump  Mesenteric bed – Truncal obesity Hypothyrodism –  Wt. gain inspite of poor appetite  Mainly due to fluid retention
37. 37.  Insulinoma-  Wt. gain as a result of over eating to avoid hypoglycemic symptoms Craniopharyngioma –  Tumor arising from Ratheke‟s pouch  Pressure effect on hypothalamus - Obesity
38. 38. Management of obesity Goal is to reduce or prevent co- morbidities. Diet Therapy Physical Activity Therapy Behavioral Therapy Pharmacotherapy- Sibutramine, Orlistat, Rimonaba nt Surgery-.
39. 39. A. Laparoscopic gastric band (LAGB) B. The Roux-en-Y gastric bypass.
40. 40. C. Biliopancreatic diversion withduodenal switch. D. Biliopancreatic diversion.
41. 41.  Worldwide obesity has more than doubled since 1980. In 2008, 1.5 billion adults, 20 and older, were overweight. Of these over 200 million men and nearly 300 million women were obese. 65% of the worlds population live in countries where overweight and obesity kills more people than underweight. Nearly 43 million children under the age of five were overweight in 2010. Obesity is preventable.
42. 42. Remember me?
43. 43.  Robbins Pathologic Basis of Disease 8th edition Harrison’s Internal Medicine 17th edition WHO - Obesity and overweight http://www.who.int/mediacentre/factsheets/fs311 /en/index.html Wikipedia