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The Aetiology of ObesityA New Hope – Part 1 of 6
William Banting 1796-1878
Avoid ‘fattening’ carbohydrates“Letter on Corpulence” 1863
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William Osler
“Father of Modern Medicine”
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Common Knowledge
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”
FatteningCarbohydrates Obesity
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The Great Epidemic of Coronary Disease
1950s - “Diet-Heart” Hypothesis1960s - Jean Mayer carbohydrate-restricted diets “The equivalent of mass murder”
Fattening carbohydrate suddenly transformed into the healthy whole grain
Created in 1948
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Dietary Goals For the United States 1977
Dietary Goals 1. Raise consumption of carbohydrates until they constituted 55-60% of calories2. Decrease fat consumption from approximately 40% to 30% of which no more than 1/3 from saturated fat
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Food Pyramid
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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’
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How did we do?
Average fat intake decreased from 45% of calories to less than 35% 1976 – 1996
40% decline in hypertension28% decline in hypercholesterolemia
1979-1994 Smoking drops 33% to 25%
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Jus’ Doin’ what we’re told…
Source www.nusi.org
Increasing Sugar Consumption
Increasing availabilityof sugar
DietaryGuidelines
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Increasing grain consumption
1950-59 1960-69 1970-79 1980-89 1990-99 20000
50
100
150
200
250
155.4142.5 138.2
157.4
190.6 199.9
125.7114.4 113.6
122.8141.8 146.3
Total GrainWheat
Per C
apita
com
sum
ption
(lbs
)
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1st Dietary Guidelines for Americans
Caloric Reduction As Primary
Personal ChoiceBehaviour Obesity
Eat too much
Exercise too little
1. “A calorie is a calorie” 2. Fat stores are essentially unregulated
A ‘dump’ for excess calories
3. Intake and Expenditure of calories are under conscious controlIgnores effects Hunger and basal metabolic rates
4. Intake and Expenditure of calories are independent of each other
Implicit Assumptions
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Energy Balance Paradigm
Accumulation of fat due to caloric imbalance“First Law of Thermodynamics”
Cause of overeating/ underactivity is BEHAVIOURAL
Calories in/ Calories out model
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Popular Theory
Obesity is not a medical condition, but a psychological, character defect ‘low willpower’
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Experts say… Eat Less and Exercise MoreJoslin’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”
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An easily tested hypothesis
Key Assumption – Caloric intake and expenditure are independent of each other
Personal ChoiceBehaviour Obesity
Eat too much
Exercise too little
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Elusive Benefits of Under-eating
Semi-starvation diets of 1400-2100 cal/day“almost impossible to keep warm, even with an excessive amount of clothing”
30% decrease in metabolism Excess eating immediately after experiment - Weight regain
Carnegie Institution of Washington’s Nutrition Laboratory1917
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The Biology of Human Starvation
1570 calories per day
Resting metabolic rates declined by 40 percent
Heart volume shrank by 20 percentHeart rate slowedBody temperatures dropped
1944 Ancel KeysUniversity of Minnesota
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Changes in Energy Expenditure Resulting from Altered Body WeightRudolph L. Leibel NEJM 1995 march 9, 332 (10); 621-28
Changes in Energy Expenditure
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Response to weight change
Leibel RL et al. N Engl J Med 1995;332:621-628.
Reduced Energy Expenditure
Long-term persistence of adaptive thermogenesis in subjects who have maintained a reduced body weight
Maintained weight loss of 10% over 1 year
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Mean (±SE) Changes in Weight from Baseline to Week 62.
Sumithran P et al. N Engl J Med 2011;365:1597-1604
Hormonal Changes
Long-Term Persistence of Hormonal Adaptations to Weight LossN Engl J Med 2011; 365:1597-1604October 27, 2011
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Long term persistence of hormonal mediators of hunger after weight loss
Increased Hunger
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Body Weight “Thermostat”
Adaptions to weight loss:1) Reduced energy expenditure2) Increased hunger
10% increaseweight
10% decreaseweight
16% increaseEnergy expended
15% decrease Energy expended
Weight Regain!
Increased hormonalSignals of hunger
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Caloric Reduction as Primary
Coal
Storage
Power plant
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Eat less…
Randomized controlled trial
19,541 low-fat diet 29,294 usual diet
Low-fat dietary pattern and weight change over 7 years: the Women's Health Initiative Dietary Modification TrialHoward BV et al. JAMA 2006; 295:39-49
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Exercise more…
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What happened?
Normal Diet
Eat LessExercise More
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What happened?Women should have lost 36 pounds of fat in the first year alone!
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The Cruel HoaxA perfect 35 year record unblemished by success
Caloric deprivation triggers 2 adaptive mechanisms
1. Reduced energy output2. Increased hunger
The Cruel Hoax of the low fat, calorie-restricted dietTHEY DON’T WORK!
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Vicious Cycle of Under-eating
Eat Less Calories
Lose Weight
Decreased Energy ExpenditureIncreased Hunger
Regain Weight
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The Overeating Paradox
Metabolism increased by 50%
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The Overfeeding Paradox
Metabolic response to experimental overfeeding in lean and overweight healthy volunteersAm J Clin Nutr Oct 1992;56(4): 641-55 Diaz EO
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The Overfeeding Paradox
Metabolic response to experimental overfeeding in lean and overweight healthy volunteersAm J Clin Nutr Oct 1992;56(4): 641-55 Diaz EO
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Caloric Reduction
Eat Less
Eat More
Weight Loss
Weight Gain
Caloric deprivation is difficult because it is a fight against mechanisms which have evolved to precisely minimize its effects
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The Ultimate Proof…
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Exercise More…
“Experts” routinely claim that exercise is the key to weight loss
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Exercise More…
Source: wholehealthsource.blogspot.ca
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Exercise does not lead to increased weight loss
Prospective cohort study 39 876 women 1992-2004Physical Activity and Weight Gain Prevention, Women’s Health StudyJAMA 2010;303(12): 1173-1179 Buring et al
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Exercise and Weight Loss
>21 7.5-21 <7.5
-0.15
-0.1
-0.05
0
0.05
0.1
0.15
0.2
0.25
0.3
<5555-64>65
Kg w
eigh
t los
s
Reference
Physical Activity and Weight Gain Prevention, Women’s Health StudyJAMA 2010;303(12): 1173-1179 Buring et al
Age
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No Weight Loss
Changes 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 e4515
No difference in any of the group in weight lost!
Randomized to 0, 72, 136, 194 min/wk exercise
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Minimal Weight LossExercise Effect on Weight and Body Fat in Men and WomenMcTiernan et al, Obesity (2007) 15, 1496-1512
12 month randomised, controlled trial6 days per week of 1 hour
Results 1.4 kg! (3 pounds) – women1.8 kg! (4 pounds) - men
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Marathons must work….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 GM
ResultsMen – average weight loss 5 pounds9 women – no weight lost
“no change in body composition was observed”
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CompensationMultiple studies lasting more than 25 weeks that average weight loss was only 30% of predicted*Possible mechanisms
1. 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: S521-527 2001
Church et al 2009 PLos www.kidneylifescience.ca
PhysEdEuropean Congress on Obesity 2009Alissa FremeauxMeasured physical activity of 206 children aged 7-8 by accelerometer
Averaged 9.2 hours per week of physical education in schoolNo difference in total weekly activity
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Compensation – mechanisms
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Exercise More…Baseline Energy Expenditure for 140 pound person:2200-2500 calories/day
Caloric expenditure 45 minute walk (2 miles/hour):
102 calories – 4% of daily caloric intake
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Exercise is not the Key
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Hypothesis
Not True!
BehaviourGluttony/Sloth
ObesityEat too much
Exercise too little
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Hormonal Obesity Theory
Insulin(cortisol)
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An Easily tested hypothesis
HighInsulin(cortisol)
LevelsObesity
Eat too much
Exercise too little
Implicit Assumptions
1) Fat, like all body systems, are regulated under hormonal control2) Intake and Expenditure of calories are under hormonal control
Hunger/ Basal metabolic Rate3) Intake and Expenditure of calories are linked to each other
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Insulin – fattening agent
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I can make you fat…
The percentage of adult men (a) and women (b) with major weight gain (increase in BMI of more than 5 kg/m 2 ) receiving intensive (white bars) or conventional (black bars) insulin therapy in the DCCT. The overall pattern of differences over time was significant (p < 0.01) for both sexes (DCCT 2001). © 2001 Diabetes Care 2001, 24: 1711–172
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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;24:1711-21
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)
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Insulin and Weight gain
Intensive Conventional Insulin Therapy for Type II Diabetes Diabetes Care 16:21-31 Henry RR
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Insulin and Weight Gain
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Insulin and Weight Gain
Addition of Biphasic, Prandial, or Basal Insulin to Oral Therapy in Type 2 DiabetesN Engl J Med 2007;357:1716-30 Holman RR
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Insulin Lipohypertrophy
‘Lipogenic’ effect of insulin – self injections of insulin can lead to masses of fat at site of injection
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Insulin and oral hypoglycemics
The American Journal of Medicine 108, Issue 6, Supp 1, 17 April 2000, Pages 23–32 John Buse et al
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Long-Term Efficacy of Dapagliflozin in Patients With Type 2 Diabetes Mellitus Receiving High Doses of Insulin: A Randomized Trial
Ann Intern Med. 2012;156(6):405-415
Change in daily dose of insulin Change in Weight
Insulin and Weight Gain
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Metformin is Weight Neutral
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Januvia
DPP4 inhibitors increase glucose dependent insulin release
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Dapaglifozin
Effects 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 MetforminJ Clin Endocrinol Metab 97: 1020–1031, 2012
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J Clin Endocrinol Metab 97: 1020–1031, 2012
Fat Loss
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Drugs that increase basal insulinIncrease
• Insulin• Sulfonylureas
• Glyburide• Glicizide
No Increase
• Metformin• DPP IV inhibitors
• Januvia• Onglyza• Trajenta
• SGLT – 2
With exception of TZD class
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Drugs that cause weight gain
Increase
• Insulin• Sulfonylureas
• Glyburide• Glicizide
No Increase
• Metformin• DPP IV inhibitors
• Januvia• Onglyza• Trajenta
• SGLT – 2
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I can make you thin…
Untreated and treated Type 1 Diabetes Mellitus
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Diabulimia
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 loss
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I can make you fat…Excess cortisol result in weight gain
Exogenous – steroids, prednisoneEndogenous – Cushings syndrome
”the hallmark sign of Cushing's syndrome is accelerated weight gain”
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I can make you thin….
“Most patients with Addison's disease experience fatigue, generalized weakness, loss of appetite and weight loss”
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Hormones are the Key!Insulin = WeightInsulin = Weight
Cortisol = WeightCortisol = Weight
What makes us fat?
Eat too muchExercise too littleHormones! Obesity is a hormonal dis-regulation of fat!
Insulin (cortisol)www.kidneylifescience.ca
Caloric Reduction As Primary
Uninterrupted 35 year string of failure in treatment of obesity “a perfect record - unblemished by success”
BehaviourGluttony/Sloth
ObesityEat too much
Exercise too little
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Hormonal Theory of Obesity
We do not get fat because we overeatWe overeat because we get fat!
HighInsulin(cortisol)
Levels
ObesityEat too much
Exercise too little
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The Aetiology of Obesity
What is driving my insulin (cortisol) levels up?
Answer – The fattening carbohydrates
FatteningCarbohydrates
High InsulinLevels
Obesity Over-eatingUnder-activity
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Banting’s understanding
FatteningCarbohydrates Obesity
FatteningCarbohydrates
IncreasedInsulin Levels
Obesity
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Obesity Set Point
Insulin adjusts the “body weight setpoint”
Body acts as a thermostat not a scale
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The Practice of Endocrinology 1951Food 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 sweets
You 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
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