Successfully reported this slideshow.
We use your LinkedIn profile and activity data to personalize ads and to show you more relevant ads. You can change your ad preferences anytime.

Obesity

Management of Obesity

  • Be the first to comment

  • Be the first to like this

Obesity

  1. 1. Kyaw Soe win, Asso Prof / Senior Consultant Cardiologist Vintage Luxury Yachet Hotel, 30 May 2015
  2. 2. Treating Patients with Obesity: Who, Why, How and to What Ends
  3. 3. Guide for Selecting Obesity Treatment The Practical Guide: Identification, Evaluation, and Treatment of Overweight and Obesity in Adults. October 2000, NIH Pub. No.00-4084 Treatment 23-26.9 27-29.9 30-34.9 35-39.9 >40 Diet, Exercise, Behavior Tx + + + + + Pharmaco- therapy With co- morbidities + + + Surgery With co- morbidities + BMI Category (kg/m2) Take Home Massage
  4. 4.  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)  Obesity can be defined as an excess of body fat accumulation or adiposity, with multiple organ-specific adaptive or maladaptive consequences, and has been considered more prone to develop cardiovascular diseases.
  5. 5. • Calling it a disease would define one-third of Americans as being ill and could lead to more reliance on costly drugs and surgery rather than lifestyle changes • Some people might be overtreated because their BMI was above a line designating them as having a disease, even though they were healthy Why Obesity is NOT a Disease • It is a lifestyle choice • No specific symptoms associated with it • It is a risk factor for disease, not a disease itself* * What about high cholesterol or hypertension?
  6. 6. Why Obesity IS a Disease • It is associated with impaired body function • Like other diseases, it results from physiological dysfunction (precipitated by numerous forces in modern society) • It causes, exacerbates or accelerates more than 65 significant comorbid diseases • It is associated with a substantial burden of morbidity and premature death
  7. 7. 7 Consequences of Obesity Hippocrates recognized that : “sudden death is more common in those who are naturally fat than in lean.” (in BC 400)
  8. 8. Complications of Obesity Several of these complications exacerbate the underlying obesity, creating a vicious cycle: Diabetes Many diabetes drugs cause weight gain PCOS Insulin resistance promotes lipogenesis Sleep apnea Disrupted sleep can cause weight gain Arthritis Limit exercise capacity Back pain Inflammatory Steroids often cause disorders weight gain Depression Eating disorders and Psychological many psychotropic agents cause weight gain Psychological Neoplastic Inflammatory Structural Metabolic Degenerative
  9. 9. Medical Complications of Obesity Phlebitis venous stasis Coronary heart disease Pulmonary disease abnormal function obstructive sleep apnea hypoventilation syndrome Gallstones Gout Diabetes Osteoarthritis Fatty liver disease steatosis steatohepatitis cirrhosis Hypertension Dyslipidemia Cataracts Skin disorders Pancreatitis Intracranial hypertension Cognitive dysfunction Cancer breast, uterus, cervix, ovary, prostate, kidney, colon, esophagus pancreas, gallbladder, liver Gynecologic abnormalities abnormal menses infertility polycystic ovarian syndrome Stroke
  10. 10.  Affects men and women of all ages  Predominates in developed countries. obesity?
  11. 11. PREVALENCE OF RISK FACTORS FOR NON-COMMUNICABLE DISEASES IN MYANMAR Risk Factors Yangon* (2003-2004) (%) National** (2009) (%) Male Female Both Sexes Male Female Both Sexes Current smoking 36.00 11.11 23.20 33.61 6.13 16.68 Current drinking 25.96 1.09 11.96 31.17 1.47 12.87 Physical inactivity 7.32 7.86 7.62 10.44 14.1 12.69 Fruits and vegetable consumption (% Who eat 5servings of fruits and vegetables/day) 98.64 98.73 98.69 89.8 90.6 90.29 Hypertension 27.94 24.11 25.87 30.99 29.34 29.97 Overweight (BMI 25) 20.60 29.96 23.80 17.74 30.27 25.38 Obesity (BMI 30) 4.77 10.35 7.85 4.27 8.37 6.8 Raised Blood cholesterol level (5.2mmol/L) 21.16 35.12 27.42 - - - Diabetes (diagnosed by OGTT) 11.51 12.64 12.14 - - - *STEP Survey in Yangon Division (2003-2004) ** National STEP Survey (2009) ((Prof. TSLatt et al, JAFES vol 26 no 2, November 2011)
  12. 12. Assessment of Overweight and Obesity  Body Mass Index (BMI)  Weight (kg)/height (m2)  Weight (lb)/height (in2) x 703  Waist Circumference (WC)  High risk:  Men >102 cm (40 in.)  Women >88 cm (35 in.)  Waist Hip Ratio (WHR)  Skin-fold thickness  Measurement of Abdominal Fat by CT
  13. 13. Classification BMI (kg/m2) Risk of co-morbidities Underweight <18.5 Low (but risk of other clinical problems increased) Normal range 18.5-24.9 Average Overweight* ≥25 Pre-obese 25.0-29.9 Mildly increased Obese >30.0 Class I 30.0-34.9 Moderate Class II 35.0-39.9 Severe Class III 40.0 Very severe WHO Classification of adult categories of BMI Clinical Guidelines on the Identification, Evaluation, and Treatment of Overweight and Obesity in Adults: The Evidence Report. NIH Publication # 98-4083, September 1998, National Institutes of Health.
  14. 14. Classification BMI (kg/m2) Risk of co-morbidities Waist circumference < 90 cm (men) < 80 cm (women) ≥ 90 cm (men) ≥ 80 cm (women) Underweight <18.5 Low (but risk of other clinical problems increased) Average Normal range 18.5-22.9 Average Increased Overweight ≥23 At risk 23.0-24.9 Increased Moderate Obese I 25-29.9 Moderate Severe Obese II ≥ 30.0 Severe Very severe World Health Organization, 1998 WHO classification of BMIs for adults of Asian origin
  15. 15.  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
  16. 16. Limits of using BMI  BMI is not an index of regional fat distribution  BMI may overestimate body fat in athletes and individuals with a muscular build  BMI DOES NOT  show the difference between excess fat and muscle.  identify whether the fat is laid down in particular sites. eg, abdominal fat has more serious health consequences than fat located elsewhere  BMI may underestimate body fat in older persons and individuals who have lost muscle mass
  17. 17. Measuring Waist Circumference Waist circumference is calculated by comfortably measuring the waist halfway between the bottom of the rib cage and the top of the pelvis.
  18. 18. Measuring Waist Circumference  WC is a good surrogate index of visceral adiposity.  WC is an independent and powerful risk factor for CAD and MI.  WC is related to increased risk of DM, hypertension, stroke, sleep apnoea and dyslipidaemia. Increased risk Substantially increased risk Men 94 cm 102 cm Women 80 cm 88 cm
  19. 19. Country/Ethnic group Waist circumference Europids Male Female ≥ 94 cm ≥ 80 cm South Asians Male Female ≥ 90 cm ≥ 80 cm Chinese Male Female ≥ 90 cm ≥ 80 cm Japanese Male Female ≥ 90 cm ≥ 80 cm Ethnic South and Central Americans Use South Asian recommendations until more specific data are available Sub-Saharan Africans Use European data until more specific data are available Eastern Mediterranean and Middle East (Arab) populations Country/ethnic specific values for waist circumference
  20. 20. Measuring obesity Measuring Waist Circumference  Large waist circumference (WC) can identify some at increased risk over BMI alone  If BMI and other cardiometabolic risk factors are assessed, currently there is insufficient evidence to:  Substitute WC for BMI  Measure WC in addition to BMI Klein, et al. Waist Circumference and Cardiometabolic Risk. Diabetes Care. 2007 0: dc07-9921v1-0.
  21. 21. 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
  22. 22. Waist-to-hip ratio Ratio = WAIST HIPS TO FIND RATIO Waist: Measure at narrowest point with stomach relaxed Hips: Measure at fullest point Desired Ratio Women : <0.8 Men : < 1.0 Risk increases if waist circumference is >94 cm in men and >80 cm in women
  23. 23. 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)
  24. 24. Measuring Abdominal Fat by CT
  25. 25. ta&jym;atmufwGiftqDydkrsm;pka0;wwfonfhae&mrsm;  Insert figure 10.1
  26. 26. Obesity Phenotypes  Peripheral adiposity  Collection of fat on hips and buttocks  Women are more likely to have a peripheral distribution  Associated with mechanical problems  Abdominal adiposity or central obesity  More likely to have a waist distribution  Associated with insulin resistance and heart disease  Mixed central – peripheral adiposity  Severely obese women and men ( BMI >40 kg/m2)
  27. 27. Peripheral adiposity central obesity
  28. 28. Measuring Waist Hip Ratio
  29. 29. •Mixed central – peripheral adiposity
  30. 30. “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)
  31. 31. WHY is it HARD to maintain the weight loss for those who lose after dietary restriction? - Constant number of adipocytes - -Higher no. in obese
  32. 32. Fat Cells  Adipose cells store majority of the body’s fat. Vary in size and number.  Increase in body fatness is due to:  Fat cell hypertrophy  Fat cell hyperplasia Fat Cell Number  Number of fat cells appears to be biggest factor in determining risk for obesity.  Determined mostly in adolescent years  Average non-obese person: 25-30 bill.  Moderately obese: 60-100 bill.  Massively obese: 300 bill. +  Fat cells development (significant ):  Last trimester of pregnancy  First year of life  During adolescent “growth spurt”
  33. 33. ..
  34. 34. Fat Cells and Weight Gain  Typically only see an increase in size of existing cells in adults. (Hypertrophy)  If cells begin to reach their maximum size of 1.0 micrograms of lipid per cell then new cells may develop. (Hyperplasia) Fat Cells and Weight Loss  Cells decrease in size, not number:  Studies have proven, fat cells ONLY decrease in size not number.  Individuals with higher number of cells, regained weight more readily.  Person’s with smaller, more numerous cells reported more “cravings” for food  Leptin? Development of Adipose tissues As expected, studies have shown that nutritional and exercise interventions in the growing years, results in a LOWER FAT CELL NUMBER, and a subsequent decrease in relative RISK of obesity!!!
  35. 35. All Fat Cells Are Not Created Equal • Large Insulin- Resistant Adipocytes • Adrenergic Receptors  • Insulin-Mediated Antilypolysis • Catecholamine- Mediated Lipolysis  • Small Insulin-Sensitive Adipocytes • Adrenergic Receptors  Fatty Acids 
  36. 36. Adipose Tissue is an Endocrine Organ!!!
  37. 37. LEPTIN ADIPONECTIN INTERLEUKIN-6 Cortisol (11betaHSD) Angiotensinogen Angpt4/PGAR/FIAF SAA2 Retinol Binding Protein Adipokines (adipose hormones) and other key secretory products produced by fat cells.
  38. 38. LEPTIN ADIPONECTIN INTERLEUKIN-6 Cortisol (11betaHSD) Angiotensinogen Angpt4/PGAR/FIAF Serum Amyloid A Omentin Visfatin Adipokines are also produced by non-adipose cells within adipose tissue. TNF-ALPHA Interleukin-8 PAI-1
  39. 39. Resistance Hyperinsulinemia + Hyperglycemia Activation of the sympathetic nervous system Increase of arterial tone Na+ reabsorption Hypertension Overstimulation of pancreatic -cell function Reduction of insulin secretion Type 2 Diabetes
  40. 40. Risk Factor Defining Level Abdominal obesity Men Women Waist circumference >102 cm (>40 in) >88 cm (>35 in) Triglycerides ≥150 mg/dL (1.7 mmol/L) HDL cholesterol Men Women <40 mg/dL (1.04 mmol/L) <50 mg/dL (1.29 mmol/L) Blood pressure ≥130/ ≥85 mmHg Fasting glucose ≥100 mg/dL (5.6 mmol/L) In order to make a diagnosis of the metabolic syndrome a patient must present with three or more of the following five risk factors: Metabolic syndrome: The NCEP ATP III definition* *2001, updated 2005
  41. 41. Metabolically Healthy Obesity Features of MHO subjects  Predominant subcutaneous peripheral adiposity  Younger age when compared with complicated obese subjects  Normal fasting glucose and glucose tolerance  Normal systolic and diastolic BP (≤120/80 mmHg)  Normal lipid profile, including normal levels of TG (≤150 mg/dl) and HDL cholesterol (≥40 and ≥50 mg/dl in men and women, respectively) The existence of MHO subjects is a well-defined clinical entity.
  42. 42.  when compared with complicated obese subjects  Lower prevalence of small LDL particles  Better insulin sensitivity  Lower inflammatory status  Normal liver enzymes  Normal resting electrocardiogram  Appropriate echocardiographic left ventricular mass or no LV hypertrophy  Low c-IMT  No clinical evidence of coronary artery disease or heart failure Metabolically Healthy Obesity Features of MHO subjects
  43. 43.  MHO subjects show a more prevalent subcutaneous, peripheral obesity phenotype rather than the central, visceral obesity phenotype.  MHO subjects also need clinical management and weight loss strategies similar to morbidly obese subjects.  Their better insulin sensitivity and lower visceral adiposity may contribute to a better response to weight-loss interventions. Metabolically Healthy Obesity Management of MHO subjects
  44. 44. Managing the Obesity
  45. 45. 48 What causes Obesity?  Genetics  Nutrient and Energy model of obesity:  Energy output (physical activity)  Energy input (dietary intake)  Behavioral and cultural factors  Medications
  46. 46. rsdK;&d k;ADZ bmhaMumifh]0} wmvJ
  47. 47. Genetic Links  Study in Cambridge University has isolated at least two genes that when manipulated…control weight gain / loss (Leptin)  Genetics account for ~40% of weight differences  Genes affect metabolic rate, fuel use, brain chemistry  A child with no obese parents has a 10% chance of becoming obese  A child with 1 obese parent has a 40% chance  A child with 2 obese parents has a 80% chance
  48. 48. bmhaMumifh]0} wmvJ ygwf0ef;usif
  49. 49. tcsdK ESifh tqDtqdrfYrsm;aomtpm;taomufrsm; aygrsm;jcif;
  50. 50. tcsdK ESifh tqDtqdrfYrsm;aom tpm;taomufrsm;aygrsm;jcif;
  51. 51. tcsdK ESifhtqDtqdrfYrsm;aom tpm;taomufrsm;aygrsm;jcif;
  52. 52. tcsdKESifh tqDtqdrfYrsm;ao m tpm;taomufrsm; aygrsm;jcif;
  53. 53. qDrsm;rsm;eJY<uyf<uyfaMumfjcif;
  54. 54. acwfrDypönf;rsm;
  55. 55. acwfrDypönf;rsm;
  56. 56. acwfrDypönf;rsm;
  57. 57. aeYpOf aexdkifrSk"avYp&dkuf
  58. 58. tpm;MuL;jcif;
  59. 59. q&musGefawmf bma&m*gjzpfwmvJ yg;pyfxJrSm tpm;rjywfwJha&m* gac:ouGJY tdrf;... tpm;MuL;jcif;
  60. 60. ttdyfrsm;jcif;
  61. 61. ttdyfrsm;jcif;
  62. 62. ttdyfrsm;jcif;
  63. 63. udk,fvufvSkyf&Sm;rSkenf;jcif;?ttdyfrsm;jcif;
  64. 64. Obesity results from a failure of normal weight and energy regulatory mechanisms
  65. 65. Berthoud HR. Curr Opin Neurobiology 2011;21:888-896
  66. 66. Satiety Regulator The hypothalamus When feeding cells are stimulated, they signal you to eat When satiety cells are stimulated, they signal you to stop eating Sympathetic nervous system When activity increases, it signals you to stop eating When activity decreases, it signals you to eat
  67. 67.  Produced by adipocytes  Product of ‘ob’ gene  Provides signal for “energy sufficiency”.  Abundant fat  Leptin secretion  Regulated by insulin stimulated glucose metabolism  Stimulates thermogenesis, activity, energy expenditure Leptin + POMC/CART neurons Anorexic neuropeptides- (MSH) Leptin - NPY/AgRP neurons Produce orexinergic neuropeptides
  68. 68.  Produced mainly by adipocytes  Low levels in obesity  Stimulates fatty acid oxidation  “Fat-burning molecule”  “Guardian angel against obesity”  ↓ fatty acid influx in liver, liver glucose production  ↓ Protects against Metabolic syndrome Adiponectin AdipoR1, AdipoR2 in skeletal muscle, liver, brain + cAMP activated protein kinase Inactivates acetyl coenzyme A carboxylase (Key enzyme in Fatty acid synthesis)
  69. 69. GI Hormonal influence Peptide Where synthesized Effect on feeding Ghrelin Stomach Orexigenic CCK Duodenum Anorexigenic PYY Distal small intestine Anorexigenic GLP-1 Small intestine Anorexigenic Amylin Pancreas Anorexigenic CCK = cholecystokinin; PYY = polypeptide YY; GLP-1 = glucagon-like peptide 1; [exenatide, liraglutide]; Amylin [pramlintide]
  70. 70. “Age and Obesity”  Greatest fat gain is from 25 – 44 years of age in most people.  Average man will gain 0.2 to 0.8 kg per year. This equates to an average of over a pound a year.  14% of all women will gain over 30 lbs from age 25 to 34.
  71. 71. Medication-induced Weight Gain Medications account for 5-10% of obesity in the U.S. In each relevant category, remove or substitute weight gain-promoting medications with weight neutral or weight loss-promoting alternatives
  72. 72. Selected Medications That Can Cause Weight Gain  Psychotropic medications  Tricyclic antidepressants  Monoamine oxidase inhibitors  Specific SSRIs  Atypical antipsychotics  Lithium  Specific anticonvulsants  -adrenergic receptor blockers SSRI=selective serotonin reuptake inhibitor  Diabetes medications – Insulin – Sulfonylureas – Thiazolidinediones  Highly active antiretroviral therapy  Tamoxifen  Steroid hormones – Glucocorticoids – Progestational steroids
  73. 73. Macroenvironmental Influences* • 24-hour lifestyle • Economic structure • Time pressures • Workload • Loss of downtime • Speed of life • Global stressors *Amenable only to societal intervention
  74. 74. Microenvironmental Influences* • Types of nutrients • Eating schedules • Physical activity • Sleep health • Drugs and medications • Local stressors *Amenable to individual action
  75. 75. The goal of lifestyle-based therapies is to normalize the patient’s microenvironment
  76. 76. Management of Obesity and Goals Goal is to reduce or prevent co-morbidities.  Short term Goal: Decrease body weight by 10 percent from baseline.  If goal is achieved, further weight loss can be attempted if indicated.  Reasonable timeline: 6 months of therapy. • Interim goal: Maintenance – May need to be continued indefinitely. • Long-term goal: If unable to lose weight, prevent further weight gain.
  77. 77. How much weight loss is significant? A 5-10% reduction in weight (within 6 months) and weight maintenance should be stressed in any weight loss program and contributes significantly to decreased morbidity
  78. 78. Benefits of Modest Intentional Weight Loss  Improvement in comorbid diseases  Type 2 diabetes  Hypertension  Dyslipidemia  Fatty liver disease  Obstructive sleep apnea  Asthma  Osteoarthritis  Cancer risk • Improved quality of life • Decreased health care costs • Decreased surgical complication rates • Orthopedic surgery • Heart surgery • General and thoracic surgery • The effect on cardiovascular risk is less clear
  79. 79. Obesity Treatment Pyramid Surgery Pharmacotherapy Lifestyle Modification Diet Physical Activity
  80. 80. Requires two steps:  Assessment  Degree of obesity  Determine absolute risk status  Management  Weight management  Weight loss  Weight maintenance  Control of associated risk factors Management of Overweight/Obese Patients
  81. 81. Assessment of Overweight and Obesity  Body Mass Index (BMI)  Weight (kg)/height (m2)  Weight (lb)/height (in2) x 703  Waist Circumference (WC)  High risk:  Men >102 cm (40 in.)  Women >88 cm (35 in.)  Waist Hip Ratio (WHR)  Skin-fold thickness  Measurement of Abdominal Fat by CT
  82. 82. Determine Absolute Risk Status Evaluate:  Disease conditions (e.g., CHD, type 2 diabetes, sleep apnea) (+ = very high risk)  Cardiovascular risk factors: smoking, hypertension, high LDL, low HDL, IGT, family h/o (>3 = high risk  Other obesity-associated diseases (e.g., gynecological abnormalities, osteoarthritis)  Other risk factors:  Physical inactivity  High serum TG (>200 mg/dL)
  83. 83. Classification Of Obesity (Clinical staging)  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
  84. 84. Treatment Algorithm Patient Encounter Hx of 25 BMI? • Measure weight, height, and waist circumference • Calculate BMI Examination Brief reinforcement/ educate on weight management Periodic weight check Advise to maintain weight/address other risk factors Clinician and patient devise goals and treatment strategy for weight loss and risk factor control Assess reasons for failure to lose weight Maintenance counseling: Dietary therapy Behavior therapy Physical activity: Treatment Assess risk factors No Yes 1 2 14 15 13 12 11 1016 3 4 6 5 7 8 9 Yes No Yes No Hx BMI 25? No Yes Yes No Does patient want to lose weight? Yes No Progress being made/goal achieved? BMI 25 OR waist circumference > 88 cm (F) > 102 cm (M) BMI  30 OR {[BMI 25 to 29.9 OR waist circumference >88 cm (F) >102 cm (M)] AND 2 risk factors} BMI measured in past 2 years?
  85. 85. No BMI ³ 30 OR {[BMI 25 to 29.9 OR waist >88 cm (F) >102 cm (M)] AND ³ 2 risk factors} Treatment Algorithm (Part 1 of 3)Patient Encounter Hx of 25 BMI? • Measure weight, height, and waist circumference • Calculate BMI Assess risk factors No Yes 1 2 3 4 6 5 7 Yes No BMI measured in past 2 years? BMI  25 OR waist > 88 cm (F) > 102 cm (M) Yes Examination Treatment
  86. 86. Devise goals and treatment strategy for weight loss and risk factor control Assess reasons for failure to lose weight Maintenance counseling 12 11 10 8 9 No Yes Yes No Desire to lose weight? Yes No Progress made? BMI 30 OR {[BMI 25 to 29.9 OR waist >88 cm (F) >102 cm (M)] AND  2 risk factors} Examination Treatment 7 Periodic weight check • Advise to maintain weight • Address other risk factors 13 16 Treatment Algorithm (Part 2 of 3)
  87. 87. • Brief reinforcement • Educate on weight management Periodic weight check • Advise to maintain weight • Address other risk factors 14 15 13 16 5 Yes No Yes No Hx BMI  25? BMI 25 OR waist > 88 cm (F) > 102 cm (M) Examination Treatment Treatment Algorithm (Part 3 of 3) * This algorithm applies only to the assessment for overweight and obesity and subsequent decisions based on that assessment. It does not include any initial overall assessment for cardiovascular risk factors or diseases that are indicated.
  88. 88. Dietary Therapy (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.
  89. 89. Why Diets Don’t Work  Obesity is a chronic disease  Treatment requires long-term lifestyle changes  Dieters are misdirected  More concerned about weight loss than healthy lifestyle  Unrealistic weight expectations  Body defends itself against weight loss  Thyroid hormone concentrations (BMR) drop during weight loss and make it more difficult to lose weight  Activity of lipoprotein lipase increases making it more efficient at taking up fat for storage  Weight cycling (yo-yo dieting)  Typically weight loss is not maintained  Weight lost consists of fat and lean tissue  Weight gained after weight loss is primarily adipose tissue  Weight gained is usually more than weight lost  Associated with upper body fat deposition
  90. 90. Clinical Application  “Doctor, I know I need to reduce my calories and exercise more in order to lose weight. I have done it more times that I would like to admit. But I get hungry and its hard to stay on a calorie reduced diet. What is it about my metabolism that causes me to be so hungry?”
  91. 91. Nutrients Influence Presence of energy yielding nutrient registers satiety in the brain Apolipoprotein A-IV on the chylomicrons signals satiety in the brain Absence of these nutrients will signal hunger
  92. 92. Behavior Therapy: Important Concepts Techniques to conquer eating triggers  eating regular meals  eating at the same time and place  use smaller plates  keeping accessible food out of sight  eating only when hungry  avoiding activities that encourage eating • slowing pace of eating • reducing portion sizes • measuring food intake • leaving food on plate • improving food choices • eliminating second servings •
  93. 93. Physical Activity, Exercise, and Physical Fitness  Physical activity: Any bodily movement produced by skeletal muscles that results in energy expenditure.  Exercise: A subset of physical activity That is planed, structured, and repetitive and is done to improve or maintain physical fitness.  Physical fitness: A set of attributes that are either health or skill related Health- endurance, strength, flexibility, Skill- balance, agility, power, reaction time, speed and coordination
  94. 94. Regular Physical Activity  Fat use is enhanced with regular physical activity  Increases energy expenditure  Duration and regularity are important  Make it a part of a daily routine
  95. 95. Physical Activity  Activity blunts the weight gain seen with aging.  Studies in active adults  No statistical relationship between caloric consumption and body fat percentage  Linear relationship between activity level and body fat%.  Reduced physical activity is the MAIN cause of adult obesity!
  96. 96. Increasing energy expenditure: exercise is very effective in preventing long term weight regain. At least, doing aerobic exercise 3-5 times /week for 45 minute Include 5-10 minute warm up and cool down
  97. 97. Pharmacological Therapies
  98. 98. Drug Treatment of Obesity: Indicated when  BMI is greater than 30  BMI is higher than 27 and there are other cardiovascular complications  After several attempts diet alone is not enough
  99. 99. Anti-Obesity Medication – General Principles  Should not be first-line in treatment of obesity  Should only be used in conjunction with a healthy eating and good exercise programme.  Should not be prescribed to children in General Practice – if all other advice on behavioural changes, exercise and diet is failing – refer to secondary care.
  100. 100. Pharmacotherapy: sibutramine  Sibutramine is a centrally acting inhibitor of serotonin and noradrenaline reuptake. A starting dose of 10 mg once daily is recommended; after 4 weeks this can be titrated to 15 mg once daily.  Sibutramine induces ≥10% loss of initial body weight in almost 50% of overweight/obese patients.
  101. 101. Treatment Options 2012 Phentermine  Short term medication Orlistat  Fat blocker with limited efficacy and well known side effects Metformin
  102. 102. Pharmacotherapy: Orlistat  Orlistat is a reversible lipase inhibitor for obesity management that acts by inhibiting the absorption of dietary fats.  Orlistat may induce ≥10% loss of initial body weight in almost 30% of obese patients.  Orlistat produces beneficial effects on cardiometabolic profile in overweight/obese individuals.
  103. 103. Orlistat - Mechanism of Action FA MG GI lipase + orlistat TG Intestinal lumen Mucosal cell Lymphatics MicelleBile acids MG 30% not absorbed FFA
  104. 104. Orlistat inhibits absorption of approximately 30% of dietary fat 30 25 20 15 10 5 0 Mean faecal fat (g/day) -5 -4 -3 -2 -1 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 Study days Guerciolini, Int J Obesity 1997; 21 (Suppl. 3): S12-23 Orlistat 120 mg tid
  105. 105. Orlistat (Xenical)  License – BMI 30+ or BMI 27+ with associated risk factors.  Continue after 3mths only if patient has lost at least 5% of body wt since starting.  Continue for longer than 12mths only after discussing benefits / limitations with pt.  Vitamin supplementation (esp D) may be considered if concern about absorption of fat soluble vitamins.
  106. 106.  Contra-indications – chronic malabsorption syndrome, cholestasis, breast-feeding  Cautions – pregnancy  Side Effects – GI – flatulence, faecal urgency and incontinence, oily stools, abdo pain and distension. Tooth and gingival disorders, fatigue, headache, anxiety.  Dose – 120mg during or up to an 1hr after a meal up to TDS. If a meal is missed or contains no fat – omit the dose of orlistat. Orlistat (Xenical)
  107. 107. Meta-analysis of RCTs Evaluating Effect of Orlistat Therapy on Weight Loss at 1-Year Study or Sub-category WMD (random) 95% CI Hollander 1998* Sjostrom 1998 Davidson 1999 Finer 2000 Heuptman 2000 Lindgarde 2000 Rossner 2000 Bakris 2002 Broom 2002 Kelley 2002* Miles 2002* Total (95% CI) Padwal et al. Int J Obes 2003;27:1437 *All subjects had type 2 diabetes WMD=weighted mean difference Favours Treatment Favours Control -10 -5 0 105
  108. 108. -12 -9 -6 -3 0 Effect of Long-term Orlistat Therapy on Body Weight 0 Weeks 52 Torgenson et al. Diabetes Care 2004;27:155 ChangeinWeight(kg) 104 156 208 P<0.001 vs placebo -4.1 kg -6.9 kg Placebo Orlistat
  109. 109. Gastrointestinal Side Effects of Orlistat Therapy Year 1 Year 2 Placebo Orlistat Placebo Orlistat Fatty/oily stool 5 31 1 8 Increased defecation 7 20 2 2 Liquid stools 10 13 5 8 Fecal urgency 3 10 2 3 Flatulence 3 7 2 3 Flatus with discharge 0 7 0 1 Fecal incontinence 0 7 0 2 Oily evacuation 1 6 0 5 Low plasma vitamin conc: Vitamin A 0.6 0.3 0.8 0 Vitamin D 0.6 5.1 0.8 3.1 Vitamin E 0.9 4.6 0 1.6 Sjostrom et al. Lancet 1998;352:167. Values are percentage of subjects.
  110. 110. Pharmacotherapy: Metformin  Metformin is an oral anti-diabetic drug that improves glucose tolerance and insulin sensitivity.  Metformin can be used alone or in combination with sibutramine, orlistat or rimonabant for weight-loss management in overweight and obese patients with and without diabetes.  Metformin significantly improves the cardiometabolic profile in overweight and obese subjects with and without diabetes.
  111. 111.  Medications approved in 2013 ● Lorcaserin ● Phentermine/Topiramate ER  Medications going to the FDA for possible approval ● Liraglutide ● Bupropion SR/ Naltrexone SR Treatment Options 2014
  112. 112. Indications and Dose • Approved by FDA, July 2012, schedule IV • Indication Weight loss in pts with BMI ≥30 kg/m2 or BMI ≥27 kg/m2 with weight-related co-morbid condition(s) • Treatment Dose Daily phentermine 7.5 mg topiramate ER 46 mg • Max Dose Daily phentermine 15 mg topiramate ER 92 mg Phentermine/Topiramate ER Phentermine and topiramate extended-release [package insert]. Mountain View, CA : Vivus; 2012. Mechanism of Action Phentermine • Sympathomimetic amine, NE release • Blunts appetite Topiramate • Increases GABA activity, antagonize AMPA/ kainate glutamate receptor, carbonic anhydrase inhibitor • Prolongs satiety Contraindications and Warnings Contraindications Pregnancy, glaucoma, hyperthyroidism, MAOIs Warnings • Fetal toxicity • Increased heart rate • Suicide and mood and sleep disorders • Acute myopia and glaucoma • Cognitive impairment • Metabolic acidosis • Creatinine elevations • Hypoglycemia with diabetes meds 2012
  113. 113. Lancet. 2011 Apr 16;377(9774):1341-52 Topiramate/Phentermine (Qsymia) Effects on Weight
  114. 114. Phentermine/Topiramate ER Improves Risk Factors and Manifestations of Cardiometabolic Disease CONQUER Study Variable Phentermine 7.5mg/ Topiramate 46 mg ER Placebo P value Waist circumference (cm)  -7.6 -2.4 <0.0001 Systolic BP (mm Hg)  -4.7 -2.4 0.0008 Diastolic BP (mm Hg) -3.4 -2.7 0.1281 Triglycerides (%)  -8.6 4.7 <0.0001 LDL–C (%) -3.7 -4.1 0.7391 HDL–C (%)  5.2 1.2 <0.0001 CRP (mg/L)  -2.49 -0.79 <0.0001 Adiponectin (µg/mL)  1.40 0.33 <0.0001 Changes from baseline to week 56 in secondary endpoints Gadde KM, et al. Lancet. 2011;377(9774):1341-1352.
  115. 115. Phentermine/Topiramate ER: EQUIP and CONQUER Most Commonly Reported Treatment Emergent Adverse Events Adverse Event (%) (N=3749) Placebo PHEN/TPM ER 3.75/23 PHEN/TPM ER 7.5/46 PHEN/TPM ER 15/92 Paresthesia 1.9 4.2 13.7 19.9 Dry mouth 2.8 6.7 13.5 19.1 Constipation 6.1 7.9 15.1 16.1 Upper respiratory tract infection 12.8 15.8 12.2 13.5 Headache 9.3 10.4 7.0 10.6 Dysgeusia 1.1 1.3 7.4 9.4 Nasopharyngitis 8.0 12.5 10.6 9.4 Insomnia 4.7 5.0 5.8 9.4 Dizziness 3.4 2.9 7.2 8.6 Sinusitis 6.3 7.5 6.8 7.8 Nausea 4.4 5.8 3.6 7.2 Back pain 5.1 5.4 5.6 6.6 Fatigue 4.3 5.0 4.4 5.9 Blurred vision 3.5 6.3 4.0 5.4 Diarrhea 4.9 5.0 6.4 5.6 Phentermine and topiramate extended-release [package insert]. Mountain View, CA: Vivus; 2012.
  116. 116. Phentermine and Topiramate Neuropsychiatric Safety  No serious AEs related to depression, anxiety or cognition  No increase in the risk of suicidality (C-SSRS*, PHQ-9**, and AE reporting) in a population where 20% had a prior history of depression  Can be prescribed in patients with stable depression and patients on SSRIs *Columbia Suicide Severity Rating Scale ** Patient Health Questionnaire 9-item depression scale Phentermine and topiramate extended-release [package insert]. Mountain View, CA : Vivus; 2012.
  117. 117. Phentermine/Topiramate  Combination gives greater effectiveness with fewer side effects  Cost: $150.00/month  Side effects: dry mouth, numbness, tingling, insomnia, dizziness, anxiety, irritability and disturbance in attention
  118. 118. Lorcaserin Lorcaserin hydrochloride [package insert]. Woodcliff Lake, NJ: Eisai Inc.; 2012. Mechanism of Action • Selective 5-HT2C receptor agonist • Stimulates α-MSH production from POMC neurons resulting in activation of MC4R • Increases satiety Indications and Dose • Approved by FDA June 2012 • Indication: Weight loss in patients with BMI ≥30 kg/m2 or BMI ≥27 kg/m2 with weight-related co- morbid condition(s) • 10 mg po bid • Schedule IV • Discontinue if 5% weight loss is not achieved in 12 wks Contraindications and Warnings Contraindications • Pregnancy Warnings • Co-administration with other serotonergic or anti- dopaminergic agents • Valvular heart disease • Cognitive impairment • Psychiatric disorders (euphoria, suicidal thoughts, depression) • Priapism • Risk of hypoglycemia with diabetes meds 2012
  119. 119. Increase in serotonin bioavailability (due to food intake or pharmacological compounds such as sibutramine and fenfluramine) or direct agonism of 5HT2CRs and 5HT1BRs modulates firing of POMC/CART and AgRP NPY neurones within the arcuate nucleus of the ARC Anorectic POMC neurones expressing 5HT2CR depolarize on receptor activation and release α-melanocyte-stimulating hormone (α-MSH), which in turn activates second-order melanocortin 4 receptor (MC4R) expressing neurones, principally within the paraventricular nucleus of the hypothalamus (PVH; Balthasar et al. 2005) Concomitant activation of 5HT1BRs expressed on orexigenic AgRP/NPY neurones within the ARC causes membrane hyperpolarization and subsequent inhibition of neuropeptide release Inhibitory 5HT1BR activation also attenuates inhibitory postsynaptic currents onto POMC/CART neurones further potentiating anorexigenesis Subsequent downstream neuroendocrine signalling promotes satiety and the cessation of food intake Garfield A S , and Heisler L K. J Physiol. 2009;587:49-60. Proposed Model of a Serotonergic Pathway Modulating Food Intake
  120. 120. Lorcaserin Phase 3 Trials • n=3,182 • 2 years tx • Dosage 10 mg QD1 1. Smith SR, et al. N Engl J Med 2010;363:245-56. 2. Fidler MC, et al. J Clin Endocrinol Metab, October 2011, 96(10):3067–3077. 3. O’Neil PM, et al. Obesity (16 March 2012) | doi:10.1038/oby.2012.66 Arena Pharmaceuticals • n=4,008 • 1 year tx • Dosage 10 mg QD2 • n=604 obese/ overweight with type 2 DM • 1 year+ tx • Dosage 10 mg BID or 10 mg QD3 128
  121. 121. Endpoint Lorcaserin Placebo P value Waist circumference (cm)  −6.8 −3.9 <0.001 SBP/DBP (mm Hg)  −1.4 / −1.1 −0.8 / −0.6 0.04/0.01 Cholesterol (% Δ) Total LDL HDL   −0.90 2.87 0.05 0.57 4.03 −0.21 0.001 0.049 0.72 Triglycerides (%)  −6.15 −0.14 <0.001 Safety HR (beats/min) Beck depression II  −2.0 −1.1 −1.6 −0.9 0.049 0.26 Lorcaserin ─ BLOOM Study: Key Secondary Endpoints Intention-to-Treat Analysis with LOCF Imputation Smith SR, et al. NEJM. 2010;363:245-256.
  122. 122. Lorcaserin: Adverse Events Reported by >5% in Any Group N (%) Lorcaserin (N = 3195) Placebo (N = 3185) Headache 537 (16.8) 321 (10.1) Dizziness 270 (8.5) 122 (3.8) Nausea 264 (8.3) 170 (5.3) Constipation 186 (5.8) 125 (3.9) Fatigue 229 (7.2) 114 (3.6) Dry mouth 169 (5.3) 74 (2.3) Smith SR, et al. NEJM. 2010;363:245-256. Intention-to-Treat Analysis with LOCF Imputation
  123. 123. Naltrexone SR/Bupropion 2011
  124. 124. Naltrexone/Bupropion • Mechanism of Action – Naltrexone ─ Opioid receptor antagonist – Bupropion ─ Dopamine/noradrenaline reuptake inhibitor • Approved by FDA committee but FDA did not approve until a CVD outcome study is performed due to concerns about blood pressure and pulse in some patients • The Light Study (CVD outcomes) is under way; estimated completion: July 2017 Apovian C, et al. Obesity. 2013. Clinicaltrials.gov. Cardiovascular Outcomes Study of Naltrexone SR/Bupropion SR in Overweight and Obese Subjects With Cardiovascular Risk Factors (The Light Study). 2012. http://clinicaltrials.gov/show/NCT01601704
  125. 125. Mean Weight Loss Greenway FL, et al. Lancet 2010 Aug 21; 376:595. DOI:10.1016/S0140-6736(10)60888-4. Naltrexone/ Bupropion 56 Weeks – Completer PopulationCOR-I Phase 3
  126. 126. Side Effects Most frequent events: – Nausea • N=171 (29.8%) naltrexone 32 mg plus bupropion • N=155 (27.2%) naltrexone 16 mg plus bupropion • N=30 (5.3%) placebo – Headache, constipation, dizziness, vomiting, and dry mouth were also more frequent in the naltrexone plus bupropion groups vs. placebo – Transient increase of ~1·5 mm Hg in mean systolic and diastolic blood pressure was followed by a reduction of around 1 mm Hg below baseline in the naltrexone plus bupropion groups – Combination treatment was not associated with increased depression or suicides vs. placebo Naltrexone/Bupropion Greenway FL, et al. Lancet. 2010 Aug 21;376(9741):595-605.PMID: 20673995.
  127. 127. Liraglutide 2010
  128. 128. Liraglutide  Glucagon-Like Peptide 1 (GLP-1) receptor agonist approved in 2010 for treatment of type 2 diabetes (1.8 mg/day)  Appetite effect mediated by both the activation of GLP-1 receptors expressed on vagal afferents and hypothalamus  Affects visceral fat adiposity, appetite, food preference, and cardiovascular biomarkers in patients with type 2 diabetes  Suppresses appetite, and delays gastric emptying  Phase III trials assessing effects of doses as high as 3.0 mg/day submitted to FDA
  129. 129. Effects of Liraglutide and Orlistat on Body Weight in Nondiabetic Obese Adults Data are mean (95% CI) for the ITT population Astrup A, et al. Lancet. 2009 Nov 7;374(9701):1606-16.
  130. 130. • Generally well tolerated and improved quality of life • Adverse events mostly mild or moderate • Gastrointestinal events (particularly nausea and vomiting), consistent with the known physiological effects of GLP-1, were more frequent than with placebo • At year 1, nausea and/or vomiting was associated with greater weight loss with liraglutide 3.0 mg, but even those who did not experience these events lost more weight than those on placebo or orlistat • Injection regimen did not impair adherence or cause significant withdrawal during treatment or run-in Liraglutide: Adverse Events Astrup A, et al. Int J Obes (Lond). Jun 2012; 36(6): 843–854.
  131. 131. Obesity Drugs in the Pipeline Beloranib Phase 2 Trial
  132. 132. Anti-obesity Medications in Development Kim GW, et al. Clin Pharmacol Ther. 2013 Oct 8. doi: 10.1038/clpt.2013.204. [Epub ahead of print]
  133. 133. Medications Approved for Obesity Medication Average Weight Loss* Mechanism of Action Potential Side Effects Phentermine (short-term treatment) ~ 5% Adrenergic Tachycardia, hypertension Phentermine / Topiramate 10% Adrenergic, CNS Tachycardia, hypertension, cognitive dysfunction, neuropathy, teratogenicity Lorcaserin 3.5% Serotonergic (5HT2C) Headache Orlistat 3% Lipase inhibitor Steatorrhea, incontinence * Beyond placebo
  134. 134. Weight Loss from Other Medications Medication Indicated Uses Comments Bupropion Depression Avoid in bipolar disease Topiramate Seizures Migraines Mood disorders May produce neurological side effects Zonisamide Seizures Mood disorders Few studies Metformin Type 2 diabetes PCOS Rare liver toxicity Liraglutide. Exenatide Type 2 diabetes Injectable Pramlintide Type 2 diabetes Injectable Pramlintide Type 2 diabetes Injectable Strategy: Aim for Double Benefits when Possible
  135. 135. Pharmacological Treatment of Obesity  Current medications 5-12% wt loss  Benefits only last as long as patient takes the medication. Chronic treatment likely needed.  Drugs probably not paid for by insurance so cost is a big issue for patients.  Issues of FDA approval, long term safety, and efficacy.  Are medications an appropriate treatment modality for obesity?
  136. 136. Practical Use of Weight Loss Medications  Understand risks, cautions and monitoring essentials  Start when weight is stable (within 3% over 3 months)  Aim for weight stability with lifestyle management  Assess effects at 1 and 3 months  Continue medication beyond 3 months if ≥ 5% total weight loss  Some use “4x3” rule - ≥ 4 lbs. weight loss/month x 3 months  Weight plateau with increased hunger is expected  Medication still working if substantial weight regain absent
  137. 137. Proper Use of Obesity Medications  Recognizing non-responders An obese patient is started on a weight loss medication and is not losing adequate amounts of weight ● STOP the medication  Lorcaserin patient should lose 5% or more of their weight by 3 months, otherwise stop  Phentermine/topiramate patient should lose 3% by 3 months or 5% by 6 months
  138. 138. The super-obese (BMI 40 + )  Incidence in U.S. population: 2.1% (4.4 million).  Increased risk of OA, cardiopulmonary failure, OSA, all consequences of metabolic syndrome (DM, NASH, HTN, hyperlipidaemia).  Medical treatment essentially hopeless, though met syndrome improves with 5-10% weight loss.  >2x mortality with BMI>40 kg/m2 due to cardiopulmonary failure, sleep apnea, diabetes
  139. 139. Gastric BypassLap Band Effectiveness Risk Low High
  140. 140. C. Biliopancreatic diversion with duodenal switch. D. Biliopancreatic diversion.
  141. 141. Comparison of Operations  Lap band: 20% weight loss, very low mortality, 1% serious or 2.4% any complication  Sleeve gastrectomy: 25% weight loss, 0.1% mortality, 2.4% serious or 6.3% any complication  Gastric bypass: 30% weight loss, 0.2% mortality, 2.5% serious or 10% any complication Ann Surg 2013;257: 791–797; Flum DR, N Engl J Med. 2009 Jul 30;361(5):445-54
  142. 142. Who is a Good Candidate?  BMI>35 with co-morbidities or >40 without  Age 20-60  Co-morbidities: Diabetes, sleep apnea, reflux > Hypertension, DJD  Failed other forms of therapy  No serious, active cardiac, pulmonary, or psychiatric disease  Must be psychologically stable and wiling to follow postoperative diet instruction  No endocrine cause for obesity  Surgical intervention work by decreasing energy intake
  143. 143. Surgical Treatment Morbidity and mortality  Mortality ranges from 0.1% for gastric banding and 0.5% for Roux-en-Y gastric bypass to 1% for biliopancreatic bypass and duodenal switch.  Laparoscopic gastric banding provides a better post-operative safety profile and therefore represents the least invasive of the frequently performed bariatric procedures.  Laparoscopic adjustable gastric banding and roux-en-Y gastric bypass are the most common bariatric surgical procedures.
  144. 144. Effect of bariatric surgery on body fatness parameters Changes After 2 years After 10 years Body weight 22% decrease 16% decrease Waist circumference 16% decrease 12% decrease BMI 22% decrease 16% decrease
  145. 145. Bariatric Surgery is Associated with a Reduced Mortality: the SOS Study Sjostrom L NEJM 2007: 357-741-752 30% lower risk Of dying MI: 25 in control Group 13 in the Surgery group Cancer: 47 in The control group 29 in the surgery group
  146. 146. Stampede Trial: Benefits of Surgery for Type 2 DM Parameter Medical Therapy (n=41) Bypass (n=50) Sleeve (n=49) P Value HbA1c<6 12% 42% 37% 0.008 HbA1C<6 without DM med 0% 42% 27% 0.003 % change in Tg -14% -44% -42% 0.08 % change in HDL 11% 28% 28% 0.001 N Engl J Med 2012;366:1567-76
  147. 147. Guide for Selecting Obesity Treatment The Practical Guide: Identification, Evaluation, and Treatment of Overweight and Obesity in Adults. October 2000, NIH Pub. No.00-4084 Treatment 23-26.9 27-29.9 30-34.9 35-39.9 >40 Diet, Exercise, Behavior Tx + + + + + Pharmaco- therapy With co- morbidities + + + Surgery With co- morbidities + BMI Category (kg/m2)
  148. 148. A Call to Action  Obesity IS a disease, regardless of its designation  Counsel patients with obesity on the risks of excess weight and the benefits of weight loss  Identify the medical comorbidities of obesity in each patient  Pursue a step-wise strategy for weight loss – lifestyle, medications and surgery as needed  Help patients maintain weight loss by optimizing the patients lifestyle – healthy diet, regular exercise, adequate sleep, stress reduction 15
  149. 149. Take-home Messages Obesity Treatment • Lifestyle adjustment is the mainstay of therapy • Medications can be effective • In selected patients • Medications work differently in different patients – requires ‘trial and error’ approach • Combination therapies look particularly promising • Go Slow and Try Different Approaches
  150. 150. Currently Available Options  Accept weight where it is  Diet/Exercise: 3-10% weight loss  Drugs: 5-12% weight loss  Medically Supervised/Combination of Diet + Drug: 10-15% weight loss  Surgery: 15-30% weight loss Low High Effectiveness
  151. 151. Currently Available Options  Accept weight where it is  Diet/Exercise: 3-10% weight loss  Drugs: 5-12% weight loss  Medically Supervised/Combination of Diet + Drug: 10-15% weight loss  Surgery: 15-30% weight loss Low High Risks/Time/Money
  152. 152.  In 2008, 1.5 billion adults, 20 and older, were overweight  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.
  153. 153. Prevention of Obesity Eat less Eat less Eat less …… ………………. Use legs
  154. 154. Health benefits Whether or not liposuction provides the health benefits commonly associated with achieving weight loss through other means is a matter of debate in scientific circles. Mainstream doctors agree that liposuction does not help to combat obesity related metabolic disorders like insulin resistance. "Liposuction does not achieve metabolic benefits of weight loss". BMJ 328 (7454): 1457–1450. doi:10.1136/bmj.328.7454.1457-a. PMC 428545. liposuction

×