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7 July 2011, Shridhan A Patil, RCC Trivandrum

   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.
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
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
   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.
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)
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
Android=Abdominal=Central=
Apple shaped

Gynecoid=Peripheral=Pear
shaped
“Super obese" male
A "super obese" male with a BMI of 47 kg/m2: weight 146 kg (322 lb), height 177 cm (5 ft 10 in)
Adipocyte Hypertrophy and/or Hyperplasia


   Endocrine

   Drugs



   Smoking cessation
What causes obesity?


   Inactive


     advertising
       neighborhood
Energy balance
 3 components
1. Afferent /peripheral system
   - Generates signals from various sites
   - Composed of leptin , adiponectin - by fat
cells, ghrelin from stomach, peptide YY (PYY) from
ileum, colon, insulin from pancreas
   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
   3. Efferent system
   Carries signals from second order neurons of
    hypothalamus to control food intake and energy
    expenditure
Peripheral Signals
   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)
   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
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)
   Produces TNF, IL-6, IL-1, IL-18, Chemokine, Steroids
   Chronic sub-clinical inflammatory state (^ CRP)
   ?Link between lipid metabolism, nutrition, inflammation

WHY is it HARD to maintain the weight loss for those who
lose after dietary restriction?
- Constant number of adipocytes
- -Higher no. in obese
..
   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
recognized that :

“sudden death is
more
common in those
who are naturally
fat than in lean.”
   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
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
↑ Adipose tissue


  ↑ Leptin

     Hypothalamus-
     ↑MSH, ↑AgRP, ↓NPY

        Increased SNS activity


             Hypertension
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
   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
   Apnoeic pauses during sleep
   Hypersomnolence at both day & night
   Polycythemia
   Eventually right sided heart falure
   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
   Strongly associated with
    Obesity, Dyslipidemia, Type 2 DM

   Presents like – Steatosis & Steatohepatitis

   10 – 20 % develop in to Cirrhosis
   Stroke
       ↑ Blood pressure
       Type 2 DM
       Elevated cholesterol levels
   Depression –
       Sleep disturbances
Bones, Joints, Cutaneous disorders
    Osteoarthritis –
      Trauma & joint malalignment,
    Gout :- ↑ Prevalence
    Skin –
      Acanthosis nigrans,
      Friability of skin, enhancing the risk of fungal &
       yeast infection
   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
   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
   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
Management of obesity
   Goal is to reduce or prevent co-
    morbidities.
   Diet Therapy
   Physical Activity Therapy
   Behavioral Therapy
   Pharmacotherapy-
    Sibutramine, Orlistat, Rimonaba
    nt
   Surgery-.
A. Laparoscopic gastric band (LAGB)




      B. The Roux-en-Y gastric bypass.
C. Biliopancreatic diversion with
duodenal switch.


                                    D. Biliopancreatic diversion.
   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 world's 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.
Remember me?
   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
Obesity

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Obesity

  • 1. 7 July 2011, Shridhan A Patil, RCC Trivandrum
  • 2.
  • 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. 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. 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. 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. 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. 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
  • 10. “Super obese" male A "super obese" male with a BMI of 47 kg/m2: weight 146 kg (322 lb), height 177 cm (5 ft 10 in)
  • 12.    Endocrine  Drugs    Smoking cessation
  • 13. What causes obesity?    Inactive    advertising  neighborhood
  • 14.
  • 15.
  • 16. Energy balance  3 components 1. Afferent /peripheral system - Generates signals from various sites - Composed of leptin , adiponectin - by fat cells, ghrelin from stomach, peptide YY (PYY) from ileum, colon, insulin from pancreas
  • 17. 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
  • 18. 3. Efferent system  Carries signals from second order neurons of hypothalamus to control food intake and energy expenditure
  • 19.
  • 21. 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)
  • 22. 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
  • 23. 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)
  • 24. Produces TNF, IL-6, IL-1, IL-18, Chemokine, Steroids  Chronic sub-clinical inflammatory state (^ CRP)  ?Link between lipid metabolism, nutrition, inflammation WHY is it HARD to maintain the weight loss for those who lose after dietary restriction? - Constant number of adipocytes - -Higher no. in obese
  • 25. ..
  • 26. 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
  • 27. recognized that : “sudden death is more common in those who are naturally fat than in lean.”
  • 28. 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
  • 29. 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
  • 30. ↑ Adipose tissue ↑ Leptin Hypothalamus- ↑MSH, ↑AgRP, ↓NPY Increased SNS activity Hypertension
  • 31.
  • 32. 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
  • 33. 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
  • 34. Apnoeic pauses during sleep  Hypersomnolence at both day & night  Polycythemia  Eventually right sided heart falure
  • 35. 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
  • 36. Strongly associated with Obesity, Dyslipidemia, Type 2 DM  Presents like – Steatosis & Steatohepatitis  10 – 20 % develop in to Cirrhosis
  • 37. Stroke  ↑ Blood pressure  Type 2 DM  Elevated cholesterol levels  Depression –  Sleep disturbances
  • 38. Bones, Joints, Cutaneous disorders  Osteoarthritis –  Trauma & joint malalignment,  Gout :- ↑ Prevalence  Skin –  Acanthosis nigrans,  Friability of skin, enhancing the risk of fungal & yeast infection
  • 39. 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
  • 40. 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
  • 41. 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
  • 42. Management of obesity  Goal is to reduce or prevent co- morbidities.  Diet Therapy  Physical Activity Therapy  Behavioral Therapy  Pharmacotherapy- Sibutramine, Orlistat, Rimonaba nt  Surgery-.
  • 43. A. Laparoscopic gastric band (LAGB) B. The Roux-en-Y gastric bypass.
  • 44. C. Biliopancreatic diversion with duodenal switch. D. Biliopancreatic diversion.
  • 45. 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 world's 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.
  • 47. 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