Transcript obesity[2]

Obesity
The Perils of Portliness
AIMGP Clinic
19 April 2005
Prepared by Damon Scales, M.D.
Updated by Sean Pritchett
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;158:1855-1867
Obesity and Pharmacologic Therapy. Endocrinol
Metab Clin N Am 2003;32:1005-10024.
Medical Consequences of Obesity. J Clin
Endocrinol Metab 2004; 89(6)
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;160:503-505
Birmingham,CL et al.How much should Canadians
eat?. CMAJ 2002;166(6):767-770
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
The Case
PMH
appendectomy
cholecystectomy
Family History
Father - MI age 54
Older brother - DM 2
Both of her parents have always been obese
No medications
The Case
Exam reveals:
moderate obesity
Weight 215 lbs (97.7 kg)
Height 5’ 6” (167.6 cm)
BMI 34.8
BP 130/76 HR 72 bpm RR 12
Cardiac Exam
JVP 3 cm
normal S1, S2, no murmurs
Remainder of examination normal
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?
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
Complex Interactions which Determine Relationship
Between Energy Intake and Expenditure
from NEJM, Aug. 7, 1997
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
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
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
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)
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
Obesity as a Risk Factor for
DMII
Bray, G.A. Medical Consequences of Obesity. J Clin Endocrinol Metab; 89(6), 2004.
The Evidence for Mortality
Significant decreases in Life Expectancy
40 y.o.
Overweight female
Overweight male
Obese
female
Obese
male
Non-smoker
3.3 y
3.1 y
7.1 y
5.8 y
Smoker
7.2 y
6.7 y
13.3 y
13.7 y
BMI at 30-49 y predicted mortality at ages 50-69
EVEN after adjustment for BMI at 50 -69 y
Mortality from obesity is affected by ethnicity
Peeters, et al. 2003 Years of Life Lost Due to Obesity. JAMA; 289:187-193.
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
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
Goals
Initial goal - reduce body weight by 10%
within ~ 6 months
For BMI 27 - 35: deficits of ~ 300-500 kcal/d will lead to
weight loss of ~ 0.23 - 0.45 kg/wk (10% in 6 mos)
For BMI > 35: deficits of ~ 500-1000 kcal/d will lead to
weight loss of ~ 0.45 - 0.9 kg/wk (10% in 6 mos)
Further weight loss can be attempted (if
indicated) after this goal is achieved
Fad Diets: The Theory
The Zone/South Beach Diet
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
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
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
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
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 stomachstapling operation?”
What do you tell her?
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
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
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
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
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
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)
Orlistat
Lancet 1998 - RCT, 743 patients, 2 years
at 1 year: -10.3 kg in orlistat group vs. -6.1 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
Surgery
Many bariatric surgical options including:
Goal is malabsorption
restriction (early satiety)
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%
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
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
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
The End