Presentation on theme: "The Aetiology of Obesity"— Presentation transcript:
1 The Aetiology of Obesity A New Hope – Part 1 of 6
2 William Banting 1796-1878 www.kidneylifescience.ca Age 62 weighed 202lbs and stood 5’5”Increased exercise and decrease caloric intake but no weight lossAte 3 meals a day of meat, fish or game with an ounce or 2 of stale toast or cooked fruit on the sideScrupulously avoided any other food that might contain either sugar or starch – in particular – bread, milk, beer, sweets, and potatoesAvoid ‘fattening’ carbohydrates“Letter on Corpulence” 1863
3 William Osler www.kidneylifescience.ca “Father of Modern Medicine” Author of seminal textbook “The Principles and Practice of Medicine” 1907Discussed treatment of obesityThese diets featured lean beef, veal, mutton and eggs1882 monograph “Obesity and Its Treatment” – insisted that fatty foods were crucial because they increased satiety and so decreased fat accumulation“Father of Modern Medicine”
4 Common Knowledge Obesity www.kidneylifescience.ca Fattening Baby and Child Care“Rich desserts, the amount of plain, starchy foods (cereals, breads, potatoes) taken is what determines … how much (weight) they gain or lose”1963 –British Journal of Nutrition“Every woman knows that carbohydrate is fattening: this is a piece of common knowledge, which few nutritionists would dispute”FatteningCarbohydratesObesity
5 The Great Epidemic of Coronary Disease 1950s - “Diet-Heart” Hypothesis 1960s - Jean Mayer carbohydrate-restricted diets “The equivalent of mass murder” Fattening carbohydrate suddenly transformed into the healthy whole grain1950s Dietary fat increasingly vilified for heart disease due to its effects on LDL cholesterol1960sthe American Medical Association were insisting that low carbohydrate diets were dangerous fads (a 200 year old fad)Low fat, high carbohydrate diets previously unknown in human historyBUT… the fattening carbohydrate could not be healthy (low fat) and unhealthy (causes obesity) at the same timeFat, with dense calories assumed to cause obesityCalories in/ calories out model displaces traditional ‘fattening carbohydrate’ modelCreated in 1948
6 Dietary Goals For the United States 1977 Dietary Goals 1. Raise consumption of carbohydrates until they constituted 55-60% of calories 2. Decrease fat consumption from approximately 40% to 30% of which no more than 1/3 from saturated fatFirst time any government institution had told Americans they could improve their health by eating less fatDietary fat controversy was now a political issue and not a scientific one
8 An Eating Plan for Healthy Americans: The American Heart Association Diet 1995 “To control the amount and kind of fat, saturated fatty acids and dietary cholesterol you eat, choose snacks from other food groups such as…low fat cookies, low-fat crackers…unsalted pretzels, hard candy, gum drops, sugar*, syrup, honey, jam, jelly, marmalade (as spreads)”*WTF??AHA endorsed ‘healthy snacks’
9 How did we do? www.kidneylifescience.ca Conscious effort to eat less fat, less red meat, fewer eggsClear evidence that the general public listened to the leading authorities of the day and tried to complyRise in obesity was not simply a case of the general public not listening to conventional medical adviceAverage fat intake decreased from 45% of calories to less than 35%1976 – 199640% decline in hypertension28% decline in hypercholesterolemiaSmoking drops 33% to 25%
14 Caloric Reduction As Primary Eat too muchPersonal ChoiceBehaviourObesityExercise too littleImplicit Assumptions1. “A calorie is a calorie”2. Fat stores are essentially unregulatedA ‘dump’ for excess calories3. Intake and Expenditure of calories are under conscious controlIgnores effects Hunger and basal metabolic rates4. Intake and Expenditure of calories are independent of each other
15 Energy Balance Paradigm Calories in/ Calories out modelTrue but completely uselessExample – crowded airport at March BreakToo many people entering, too few people leaving is the cause of the crowdingKey question is WHY?Accumulation of fat due to caloric imbalance “First Law of Thermodynamics” Cause of overeating/ underactivity is BEHAVIOURAL
16 Popular Theory www.kidneylifescience.ca Easy to understandAppeals to American sense of self-determinism – it is your ‘choice’, ‘captain of your own ship’Obesity is not a medical condition, but a psychological, character defect ‘low willpower’
17 Experts say… Eat Less and Exercise More Joslin’s Diabetes Mellitus (2005)“reduction of caloric intake” is “the cornerstone of any therapy for obesity”However, from low calorie to very low calorie diets “none of these approaches has any proven merit”Handbook of Obesity (1998)“Dietary therapy remains the cornerstone of treatment and the reduction of energy intake continues to be the basis of successful weight reduction programs”Results of such diets are “known to be poor and not long-lasting”2005 USDA Dietary Guidelines for Americans “eating fewer calories while increasing physical activity are the keys to controlling body weight”
18 An easily tested hypothesis Eat too muchPersonal ChoiceBehaviourObesityExercise too littleKey Assumption – Caloric intake and expenditure are independent of each other
19 Elusive Benefits of Under-eating Semi-starvation diets of cal/day“almost impossible to keep warm, even with an excessive amount of clothing”30% decrease in metabolismExcess eating immediately after experiment - Weight regain12 young menDecreases in BP, HR, inability to concentrate and marked weakness during physical activityreduced energy expenditure so much that if they ate more than 2100 calories/day – would start to regain weightSubjects lost weight, but constantly complained of hungerCarnegie Institution of Washington’s Nutrition Laboratory 1917
20 The Biology of Human Starvation 1570 calories per dayResting metabolic rates declined by 40 percentHeart volume shrank by 20 percentHeart rate slowedBody temperatures droppedObsessive thoughts about food, binge eating36 men put on a 24 weeks semi-starvation diet1944 Ancel Keys University of Minnesota
21 Changes in Energy Expenditure 18 obese and 23 non obese subjects with a stable weightFed a liquid diet of 40% fat, 45% carbohydrates and 15% proteinCaloric intake adjusted until weight stableSubjects then measured for energy expenditureChanges in Energy Expenditure Resulting from Altered Body Weight Rudolph L. Leibel NEJM 1995 march 9, 332 (10);
22 Response to weight change Leibel RL et al. N Engl J Med 1995;332:
23 Reduced Energy Expenditure Maintained weight loss of 10% over 1 year21 Subjects fed liquid diet of 45% carbohydratesMeasured total, resting and non resting energy expenditureDecreased energy expenditureEven 1 year after weight lossLong-term persistence of adaptive thermogenesis in subjects who have maintained a reduced body weight
24 Mean (±SE) Changes in Weight from Baseline to Week 62. Hormonal ChangesMean (±SE) Changes in Weight from Baseline to Week 62.50 patients given 10 weeks of 500 calorie liquid shakes (51% carbohydrates)Hormonal analysis after 1 year of weight lossPersistent increase in hunger signalling 1 year after weight lossLong-Term Persistence of Hormonal Adaptations to Weight LossN Engl J Med 2011; 365: October 27, 2011Sumithran P et al. N Engl J Med 2011;365:
25 Increased Hunger www.kidneylifescience.ca Long term persistence of hormonal mediators of hunger after weight loss
26 Body Weight “Thermostat” 10% increaseweight16% increaseEnergy expended10% decreaseweight15% decreaseEnergy expendedIncreased hormonalSignals of hungerPhysiological changes aimed at increasing the ‘metabolic efficiency’ and fuel supply of the tissues at a time of energy deficitThe body is smart!!Body fat is finely regulatedAdaptions to weight loss:Reduced energy expenditureIncreased hungerWeight Regain!
27 Caloric Reduction as Primary CoalPower plantStorage
28 Eat less… www.kidneylifescience.ca Randomized controlled trial 19,541 low-fat diet 29,294 usual dietstarted in 199350,000 women age enrolledDietary counselling – goal to lower fat calories from 38% to less than 20%rich in fruits, vegetables and fibreLow-fat dietary pattern and weight change over 7 years: the Women's Health Initiative Dietary Modification Trial Howard BV et al. JAMA 2006; 295:39-49
30 What happened? www.kidneylifescience.ca Normal Diet Eat Less Exercise More
31 What happened? www.kidneylifescience.ca Women should have lost 36 pounds of fat in the first year alone!
32 The Cruel Hoax www.kidneylifescience.ca A perfect 35 year record unblemished by successCaloric deprivation triggers 2 adaptive mechanisms1. Reduced energy output2. Increased hungerVirtually all studies of ‘semi-starvation’ diets are remarkably similar and unsuccessfulThe Cruel Hoax of the low fat, calorie-restricted dietTHEY DON’T WORK!
33 Vicious Cycle of Under-eating Eat Less CaloriesRegain WeightLose WeightContinues until it is intolerable – then we blame the victimDecreased Energy ExpenditureIncreased Hunger
34 The Overeating Paradox Most famous of overeating studies done in late 1960’s by endocrinologist Ethan SimsStudied convicts at Vermont State PrisonInitially raised food consumption to 4000 calories/ daygained some weight but then weight stabilizedAte up to 10,000 calories a day, while carefully controlling exerciseTook 4-6 months to increase weight by 20-25%One man less than 10 pound weight gainMost returned to normal weight with surprising rapidityMetabolism increased by 50%
35 The Overfeeding Paradox Overfed volunteers by 50% over 42 days followed by 6 weeks of monitoring46% carbohydrate dietMetabolic response to experimental overfeeding in lean and overweight healthy volunteersAm J Clin Nutr Oct 1992;56(4): Diaz EO
36 The Overfeeding Paradox Why didn’t they gain weight? Body is burning it off – increase in energy expenditureMetabolic response to experimental overfeeding in lean and overweight healthy volunteersAm J Clin Nutr Oct 1992;56(4): Diaz EO
37 Caloric Reduction www.kidneylifescience.ca Weight LossEat LessEat MoreWeight GainInduces hunger and a compensatory decrease in energy expenditureBody weight acts as if it has an ‘set point’Body acts as a thermostat NOT a scaleCaloric deprivation is difficult because it is a fight against mechanisms which have evolved to precisely minimize its effects
39 Exercise More… www.kidneylifescience.ca 1966 US Public Health Service advocated increased physical activity and diet as the best ways to lose weight1980’s “new fitness revolution” led by running and aerobics“Experts” routinely claim that exercise is the key to weight loss
41 Exercise does not lead to increased weight loss Completed health questionnaires every 6 monthsProspective cohort study womenPhysical Activity and Weight Gain Prevention, Women’s Health StudyJAMA 2010;303(12): Buring et al
42 Exercise and Weight Loss AgeAverage increase in weight loss over 3 years0.12 kgJust over ¼ pounds weight loss in 3 years!!3 years of 60 minutes per day, every day!!ReferencePhysical Activity and Weight Gain Prevention, Women’s Health StudyJAMA 2010;303(12): Buring et al
43 No Weight Loss www.kidneylifescience.ca Randomized to 0, 72, 136, 194 min/wk exerciseNo change in dietary habits24 week study duration464 womenChanges in Weight, Waist Circumference and Compensatory Responses with Different Doses of Exercise among Sedentary, Overweight Postmenopausal WomenChurch et al PLoS One (Public Library of Science) Feb 2009 Vol 4 #2 e4515No difference in any of the group in weight lost!
44 Minimal Weight Loss www.kidneylifescience.ca 6 days per week of 1 hour Exercise Effect on Weight and Body Fat in Men and WomenMcTiernan et al, Obesity (2007) 15,12 month randomised, controlled trial6 days per week of 1 hourResults1.4 kg! (3 pounds) – women1.8 kg! (4 pounds) - men102 men and 100 women – sedentarymoderate – vigorous exerciseAt baseline average weightWomen 78 kg (172 lbs)Men 96 kg (211 lbs)
45 Marathons must work…. www.kidneylifescience.ca Results Food intake and body composition in novice athletes during a training period to run a marathonInternational Journal of Sports Medicine, May 1989; 10(1 suppl.):S17-21 Janssen GMResultsMen – average weight loss 5 pounds9 women – no weight lost“no change in body composition was observed”Trained sedentary subjects to run marathon over 18 months
46 Compensation www.kidneylifescience.ca Multiple studies lasting more than 25 weeks that average weight loss was only 30% of predicted*Possible mechanisms1. Increased caloric intake2. Decreased activity outside of prescribed exercise*Ross R et al Physical activity, total and regional obesity: dose-response considerations. Med Sci Sports Exerc 33: SDifference between actual weight loss and predicted weight loss called “compensation”Church et al 2009 PLos
47 PhysEd www.kidneylifescience.ca European Congress on Obesity 2009 Alissa FremeauxMeasured physical activity of 206 children aged 7-8 by accelerometerAveraged 9.2 hours per week of physical education in schoolNo difference in total weekly activity“children who got a lot of PE time at school were compensating by doing less at home, while those who got very little PE time compensated by cranking up their activity at home, so that over the week, they all accumulated the same amount"
49 Exercise More… www.kidneylifescience.ca Baseline Energy Expenditure for 140 pound person: calories/day Caloric expenditure 45 minute walk (2 miles/hour): 102 calories – 4% of daily caloric intakeBEE estimated to calories per poundIn bed bound state caloric needs is (BEE) * 1.2Majority of calories expended is NOT exercise but basal metabolic rate – mostly used in heating the bodyWhy do we get so hungry after swimming?Why do patients on semi-starvation dietsget cold?
50 Exercise is not the Key www.kidneylifescience.ca WE SHOULD ALL GET EXERCISEBut simply not that effective for weight lossIncrease muscle toneIncrease insulin sensitivity of musclesDecrease vascular diseaseIncreased bone densityDespite 40 years of constant and utter failure ‘experts’ still insist exercise is the key to weight loss1. Burn surprising few calories with exercise – we focus on the 4% of daily caloric intake and ignore the 96% (Basal Metabolic Rate)2. Compensation effectsIncrease in appetiteDecreased other activity
51 Not True! Hypothesis Obesity www.kidneylifescience.ca Behaviour Eat too muchBehaviourGluttony/SlothObesityExercise too littleNot True!
53 An Easily tested hypothesis HighInsulin(cortisol)LevelsEat too muchObesityExercise too littleImplicit AssumptionsFat, like all body systems, are regulated under hormonal controlIntake and Expenditure of calories are under hormonal controlHunger/ Basal metabolic RateIntake and Expenditure of calories are linked to each other
54 Insulin – fattening agent Insulin discovered in 19211923 clinicians successfully used insulin to fatten chronically underweight children1930’s clinicians using it regularly in Europe and USA for pathologically underweight patientsOften gained as much as 6 pound per week using insulin and meals “rich in carbohydrates”
56 Insulin and weight gain Intensive control of type 1 DM in DCCT trial resulted in average 4.75 kg more weight gainDiabetes Control and Complications (DCCT) Trial Research Group. Influence of intensive diabetes treatment on body weight and composition of adults with type 1 diabetes in the Diabetes Control and Complications Trial. Diabetes Care 2001;24:
57 Weight gain during insulin therapy in patients with type 2 diabetes mellitus Weight gain over time in type 2 diabetes patients undergoing intensive or conventional treatment with insulin or sulfonylureas. (The Lancet, vol. 352, 1998, pp. 837–853)
58 Insulin and Weight gain 14 DM2 patients treated with intensive insulin therapyAt 6 months100 units insulin/dayDecrease of 300 calories/dayWeight gain of 8.7 kg (19lbs)!Intensive Conventional Insulin Therapy for Type II Diabetes Diabetes Care 16:21-31 Henry RR
60 Insulin and Weight Gain 708 patients on oral hypo-glycemics who added insulinIncreasing insulin dose leads to increased weightAddition of Biphasic, Prandial, or Basal Insulin to Oral Therapy in Type 2 DiabetesN Engl J Med 2007;357: Holman RR
61 Insulin Lipohypertrophy ‘Lipogenic’ effect of insulin – self injections of insulin can lead to masses of fat at site of injectionInsulin acts through LPL (Lipoprotein Lipase) – and HSL (Hormone Sensitive Lipase)
62 Insulin and oral hypoglycemics The American Journal of Medicine 108, Issue 6, Supp 1, 17 April 2000, Pages 23–32 John Buse et al
63 Insulin and Weight Gain Combination of insulin and dapaglifozinChange in WeightChange in daily dose of insulinLong-Term Efficacy of Dapagliflozin in Patients With Type 2 Diabetes Mellitus Receiving High Doses of Insulin: A Randomized TrialAnn Intern Med. 2012;156(6):
64 Metformin is Weight Neutral Metformin does not increase insulin levelsIncreases insulin sensitivityIs weight reduction related to its effect on blood glucose?
66 Dapaglifozin www.kidneylifescience.ca 24-wk multicenter, randomized, parallel-group, double-blind, placebo-controlled study182 diabetic patients with T2DMSGLT2I vs placeboEffects of Dapagliflozin on Body Weight, Total Fat Mass, and Regional Adipose Tissue Distribution in Patients with Type 2 Diabetes Mellitus with Inadequate Glycemic Control on Metformin J Clin Endocrinol Metab 97: 1020–1031, 2012
68 Drugs that increase basal insulin No IncreaseInsulinSulfonylureasGlyburideGlicizideMetforminDPP IV inhibitorsJanuviaOnglyzaTrajentaSGLT – 2With exception of TZD class
69 Drugs that cause weight gain IncreaseNo IncreaseInsulinSulfonylureasGlyburideGlicizideMetforminDPP IV inhibitorsJanuviaOnglyzaTrajentaSGLT – 2
70 I can make you thin… www.kidneylifescience.ca Type 1 diabetesAretaeus’ classic description “Diabetes is …a melting down of the flesh and limbs into urine...”Lack of insulin leads to rapid loss of weight and fatLose all fat! No matter how many calories are ingestedUntreated and treated Type 1 Diabetes Mellitus
71 Diabulimia www.kidneylifescience.ca Diabulimia (diabetes and bulimia) refers to an eating disorder in which people with Type 1 diabetes deliberately give themselves less insulin than they need, for the purpose of weight lossWell known in Type 1 DM community that a lack of insulin causes immediate and substantial weight loss
72 I can make you fat… www.kidneylifescience.ca Excess cortisol result in weight gainExogenous – steroids, prednisoneEndogenous – Cushings syndrome ”the hallmark sign of Cushing's syndrome is accelerated weight gain”Excess fat deposition due to hormonal dys-regulation – not character defect (lack of willpower)
73 I can make you thin…. www.kidneylifescience.ca “Most patients with Addison's disease experience fatigue, generalized weakness, loss of appetite and weight loss”Lack of cortisol results called Addison’s disease
74 Hormones are the Key! Eat too much Exercise too little Insulin = Weight Cortisol = WeightWhat makes us fat?Eat too muchExercise too littleHormones! Obesity is a hormonal dis-regulation of fat!Insulin (cortisol)
75 Caloric Reduction As Primary Eat too muchBehaviourGluttony/SlothObesityExercise too littleUninterrupted 35 year string of failure in treatment of obesity“a perfect record - unblemished by success”Belief in CRAP theory led to singular research focus on behavioural/ psychological issue (lack of willpower, overeating, lack of exercise)Entire generation of health professionals endorsing low fat caloric restriction as treatment
76 Hormonal Theory of Obesity HighInsulin(cortisol)LevelsEat too muchObesityExercise too littleWe do not get fat because we overeat We overeat because we get fat!Calories are primarily pushed into storage leaving inadequate amounts for energy expenditure – thus either increase caloric intake or decrease energy expenditureOvereating and under-activity are the result not the cause of obesity
77 The Aetiology of Obesity What is driving my insulin (cortisol) levels up?Answer – The fattening carbohydratesThe absolutely crucial question in obesity is not how many calories am I eatingCalories are largely irrelevant – increased caloric intake will be matched by increased caloric expenditureMore calories in, more calories outFatteningCarbohydratesOver-eatingUnder-activityHigh InsulinLevelsObesity
79 Obesity Set Point www.kidneylifescience.ca Insulin tells the body to get fat – calories and energy expenditure are adjusted to meet that goalInsulin adjusts the “body weight setpoint”Body acts as a thermostat not a scale
80 The Practice of Endocrinology 1951 Food to be avoided:1. Bread, and everything else made with flour2. Cereals, including breakfast cereals and milk puddings3. Potatoes and all other white root vegetables4. Foods containing much sugar5. All sweetsYou can eat as much as you like of the following foods:1. Meat, fish, birds2. All green vegetables3. Eggs, dried or fresh4. Cheese5. Fruit, if unsweetened, except bananas, and grapes