1. Obesity The Perils of Portliness
AIMGP Clinic
19 April 2005
Prepared by Damon Scales, M.D.
Updated by Sean Pritchett

2. References
Periodic Health Examination, 1999: Detection, prevention, and treatment of obesity. CMAJ 1999;160:513-25
Executive Summary of the Clinical Guidelines on the Identification, Evaluation, and Treatment of Overweight and Obesity in Adults. Arch Intern Med 1998;158:
Obesity and Pharmacologic Therapy. Endocrinol Metab Clin N Am 2003;32:
Medical Consequences of Obesity. J Clin Endocrinol Metab 2004; 89(6)

3. References Cont’d
A.Peeters, et al, Obesity in Adulthood and Its Consequences for Life Expectancy: A Life-Table Analysis, Ann Intern Med. 2003; 138: 24-32
Lau,D. Call for action: preventing and managing the expansive and expensive obesity epidemic. CMAJ 1999;160:
Birmingham,CL et al.How much should Canadians eat?. CMAJ 2002;166(6):

4. The Case
34 year old woman referred by family physician for opinion regarding obesity management
She states that she has been overweight for most of her life
She lives by herself, and often eats takeout
She is an executive and says it’s difficult finding time to exercise

5. The Case PMH Family History No medications appendectomy
cholecystectomy
Family History
Father - MI age 54
Older brother - DM 2
Both of her parents have always been obese
No medications

6. The Case Exam reveals: moderate obesity BP 130/76 HR 72 bpm RR 12
Weight 215 lbs (97.7 kg)
Height 5’ 6” (167.6 cm)
BMI 34.8
BP 130/ HR 72 bpm RR 12
Cardiac Exam
JVP 3 cm
normal S1, S2, no murmurs
Remainder of examination normal

7. Questions:
She wants to know if the Atkins diet is safe, and what are her risks if she does not lose weight.
Would you advise her to lose weight? How?
What are her risks associated with her level of obesity?

8. Why do people gain weight?
Beyond the scope of this seminar, but first law of thermodynamics applies…
“The amount of stored energy equals the difference between energy intake and work”
Amount of triglyceride in adipose tissue is the cumulative sum over time of the difference between energy (food) intake and energy expenditure
Current availability of highly palatable, calorically dense foods and a sedentary lifestyle promote weight gain
NEJM, Aug. 7, 1997

9. Complex Interactions which Determine Relationship Between Energy Intake and Expenditure
from NEJM, Aug. 7, 1997

10. Nature versus Nurture
Studies in twins suggest 40 to 75% of variance in BMI is attributable to genetic factors
Certain single gene disorders may result in marked obesity (Prader-Willi, Bardet-Biedl, Alstrom, etc.)
But, potent environmental influences on adiposity...
inverse relation between obesity and social class
secular trend toward increasing obesity

11. Diagnosis and Definitions
Body Mass Index = weight (kg)
height (m)2
Greater reliability than skinfold thickness indices
Cannot distinguish between increased weight due to adiposity or fluid retention
Body circumference indices
identify adults with a central (android) pattern of obesity who are at higher risk of obesity-related problems, independent of BMI
Use of these indices limited by lack of established normal reference ranges

12. Definitions
Much controversy in literature regarding definitions of overweight and obesity
Canadian Periodic Health Examination, 1999 update:
obesity defined as BMI > 27
morbid obesity defined as BMI > 35
American Medical Association, 1998 Expert Panel on Obesity
overweight defined as BMI between 25 and 29.9
obesity defined as BMI > 30

13. Scope of the Problem 64% of adults are overweight or obese.
Over past 20 yrs doubling of % obese
BMI > 27 (obesity):
35% of men, 27 % of women (Canada)
BMI > 35 (morbid obesity)
2% of men, 4% of women (Canada)
Total direct cost of obesity estimated > $1.8 billion (~2.4% of total direct medical costs)

14. Scope of the Problem Associated Conditions
Hypertension
Diabetes Mellitus
Hyperlipidemia
Coronary Artery Disease
Malignancies
Breast
Uterus
Prostate
Colon
Psychological Disorders
depression
anorexia nervosa
Bulimia
Obstructive Sleep Apnea
Osteoarthritis

15. Obesity as a Risk Factor for DMII
Bray, G.A. Medical Consequences of Obesity. J Clin Endocrinol Metab; 89(6), 2004.

16. The Evidence for Mortality
Significant decreases in Life Expectancy
40 y.o Non-smoker Smoker
Overweight female 3.3 y y
Overweight male y y
Obese female y y
Obese male y y
BMI at y predicted mortality at ages EVEN after adjustment for BMI at y
Mortality from obesity is affected by ethnicity
Peeters, et al Years of Life Lost Due to Obesity. JAMA; 289:

17. Reducing Mortality
Sustained (x 2yrs) intentional weight loss reduces all cause mortality by 20-25%.
10% reduction in weight results in:
Reduction in incidence of DM (OR 0.16)
Reduction in BP (but relapse to baseline in ~5yrs)
Reduced TG (33%), Total (9.9%), LDL (11.9%), incr. HDL

18. Therapy
Aim of weight reduction should be to decrease morbidity/mortality rather than meet cosmetic standards of thinness
Set reasonable short-term goals
Recognize that any lifestyle alterations will need to be continued indefinitely if lower body weight is to be maintained
2/3 of persons who lose weight will regain it within one year
almost all persons who lose weight will regain it within 5 years

19. Goals Initial goal - reduce body weight by 10% within ~ 6 months
For BMI : deficits of ~ kcal/d will lead to weight loss of ~ kg/wk (10% in 6 mos)
For BMI > 35: deficits of ~ kcal/d will lead to weight loss of ~ kg/wk (10% in 6 mos)
Further weight loss can be attempted (if indicated) after this goal is achieved

20. Fad Diets: The Theory The Zone/South Beach Diet Atkins
Reduced carbohydrate (into “proper zone” or mix) with increased fat content
Atkins
Very low carbohydrate (<20g/) aka high fat diet
Promotes unintentional calorie reduction through blunting of appetite. High fat content induces ketogenesis and reduces GI motility
Glycemic Index (GI) diet
Prevents high insulin secretion which acts as a direct appeteite stimulant

21. Fad Diets: The Evidence
2 RCT’s comparing low fat vs. high fat diets showed greater weight loss at 6 months for high fat diets, but no difference at 1 yr
High fat diets in short term, do not affect lipids, BP
Study of isocaloric low vs. high GI diets, showed no benefit on insulin resistance, and inconclusive data regarding weight loss

22. Exercise
Dieting is more effective than exercise in initial weight loss, but exercise is more helpful in preventing weight regain
In patients with known cardiovascular, pulmonary, metabolic disease undergo physician evaluation and graded exercise test before starting an exercise program

23. Exercise
Exercise reduces cardiovascular morbidity and mortality independent of weight loss
Blood pressure, lipids, insulin resistance all improve with exercise even in absence of weight loss
In dieting, 50% weight loss can be from lean muscle mass, causing fatigue and reducing metabolic rate, which can be attenuated by combining dieting with exercise

24. Back to the Case She returns 3 months later
She lost 2 kg in the first month, but has since regained 1 kg
She is now exercising 3 times per week (walks 30 minutes)
She asks you, “Can’t I just take a pill to lose weight? Or should I just have that stomach-stapling operation?”
What do you tell her?

25. Anorectic Drug Therapy
Pharmacologic therapy should be considered when:
Lifestyle modifications unsuccessful after 6 months
BMI > 30 or BMI > 27 with 2+ assoc. comorbidities
Contraindicated during pregnancy
Pharmacologic therapy acts by: reducing appetite, alter nutrient absorption, increase thermogenesis

26. Anorectic Drug Therapy
Dexfenfluramine and fenfluramine
serotonin-reuptake inhibitors
effective as appetite suppressants
result in weight loss when used for 6 months to 1 year
THESE DRUGS WORK!! But...
Withdrawn from market after association noted with use of these drugs and
valvular heart disease
primary pulmonary hypertension

27. Sympathomimetic Drugs
Increase catecholamines (noradrenergic) leading to decreased appetite or increased expenditure
Examples: phentermine, mazindol
phenylpropanolamine removed from OTC market by FDA after recent demonstration of risk of hemorrhagic stroke
unsuitable for obese persons with evidence of cardiovascular disease
Ephedra alkaloid containing drugs associated with incr. death, stroke, hypertension
Few studies on benefits. Avg 3-8% weight loss. Not to be used for > 12 wks

28. Sibutramine A norepinephrine and serotonin reuptake inhibitor.
Starting dose 10mg OD, titrate +/- 5mg OD
Reduce hunger, increase satiety as above N.T are anorexigenic. May also increase thermogenesis
>10 prospective RCT on efficacy

29. Sibutramine
If do not lose 2Kg (or 2%) then unlikely to benefit from higher dose
Avg weight loss of 5-8%
Weight loss maximized by 6 months
Regain of weight if drug stopped
Adverse effects: dry mouth, constipation, insomnia
Increase BP by 4mmHg systolic, 2-4mmHg diastolic
Increase HR by 4bpm

30. Orlistat Only drug available that alters fat metabolism
inhibits pancreatic lipases resulting in incomplete breakdown of ingested fat
fecal fat excretion increased (peaks at ~30% of ingested fat at dose of 120mg TID)

31. Orlistat Lancet 1998 - RCT, 743 patients, 2 years
at 1 year: kg in orlistat group vs kg
at year 2: regain of weight when orlistat stopped (though less regain than in placebo group)
63% completed trial
Side effects: (orlistat vs placebo)
fatty stool - 31% vs. 5%
increased defecation 20% vs. 7%
“oily spotting” - 18% vs. 1%
fecal urgency - 10% vs. 3%
fecal incontinence 7% vs. 0%
flatus with discharge 7% vs. 0%
Reductions in LDL, TC independent of weight loss

32. Surgery Many bariatric surgical options including:
Goal is malabsorption
Goal is restriction (early satiety)

33. Surgical Interventions
4 RCTs, 1 prospective study
long-term success in sustaining initial weight reduction which occurred in first 3-6 months
magnitude of weight loss greater than that observed with dietary/drug treatments
Post-operative mortality low (1 death in 707 patients)
Perioperative morbidity < 5%

34. Surgical Interventions
Reserved for patients
in whom efforts at medical therapy have failed
who are suffering from complications of extreme obesity
AMA recommendation:
May consider bariatric surgery in patients
with clinically severe obesity (BMI > 40)
with BMI > 35 with comorbid conditions

35. Summary Weight loss for obese patients is desirable
to help control diseases worsened by obesity (diabetes, coronary artery disease, etc.)
to help decrease the likelihood of developing the associated diseases

36. Summary The initial strategy should include
dietary therapy with reasonable goals
exercise (especially to help maintain weight loss)
Pharmacologic therapy provides only modest benefit, and often has unacceptable side effects
Sympathomimetic drugs are only marginally effective and should not be recommended to most patients
Orlistat provides modest incremental benefit in promoting weight loss, but often has intolerable GI side effects
Bariatric surgery should be considered only when lifestyle and pharmacologic therapies fail and patient is morbidly obese

37. The End