Transcript Obesity The Perils of Portliness

Obesity
The Perils of Portliness
AIMGP Clinic
14 Jan 2003
Prepared by Damon Scales, M.D.
Updated by Tim Cook (8/1/3)
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
Yanovsky et al. Obesity. NEJM 2002;346:591-602
Willett et al. Guidelines for Healthy Weight. NEJM
1999;341:427-434
References Cont’d
K.Fontaine, et al, Years of Life Lost Due to
Obesity, JAMA, 2003; 289 : 187-193
A.Peeters, et al, Obesity in Adulthood and
Its Consequences for Life Expectancy: A
Life-Table Analysis, Ann Intern Med. 2003;
138: 24-32
Health & Drug Alerts, Obesity drug
sibutramine (Meridia), CMAJ, 2002;
166(10) 1307
References
 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
 Bray,G. Drug Therapy of Obesity. UpToDate 2002.
 Davidson et al. Weight Control and Risk Factor Reduction
in Obese Subjects Treated for 2 Years with Orlistat. JAMA
1999;281:235-241
 Sjostrom et al. Randomised placebo-controlled trial of
orlistat for weight loss and prevention of weight regain in
obese patients. Lancet 1998;352:167-172
The Case
34 year old man referred by family
physician for opinion regarding obesity
management
He states that he has been overweight for most
of his life
He lives by himself, and eats mostly pre-made
meals
He works as a long-haul truck driver, and
exercises infrequently
The Case
PMH
appendectomy
inguinal hernia repair
Family History
Father - MI age 54
Older brother - DM 2
Both of his parents have always been obese
No medications
The Case
Exam reveals:
moderate obesity
Weight 250 lbs (113.6 kg)
Height 5’ 10” (177.8 cm)
BMI 35.9
BP 130/76 HR 72 bpm RR 12
Cardiac Exam
JVP 3 cm
normal S1, S2, no murmurs
Remainder of examination normal
Questions:
How would you counsel this patient?
What other conditions are associated with
obesity?
Would you advise him to lose weight? How?
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 as much as 80% 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 reproducibility 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
Obesity Pandemic! 10-20% of all people in
“rich countries”
 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)
CMAJ Feb. 23, 1999. The Cost of Obesity in
Canada
Scope of the Problem
Associated Conditions
Hypertension
Diabetes Mellitus
Hyperlipidemia
Coronary Artery
Disease
Obstructive Sleep
Apnea
Malignancies
Breast
Uterus
Prostate
Colon
 Psychological Disorders
depression
anorexia nervosa
bulimia
The Evidence for Mortality
Annals Int Med 2003 Article
Framingham Data
Signif 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
JAMA 2003 Article
Data from US Life Tables and NHANES I-III
(Nat’l Health & Nutrition Exam. Survey)
Derive YLL (Yrs Life Lost) for ages 18-85
based on BMI
Marked race and sex differences
For any degree of overweight, younger adults
had greater YLL than older
20-30 yo w.m. BMI>45 = 13 YLL (22%
20-30 yo w.f. BMI>45 = 8 YLL
Prevention
Several studies of community-based
interventions
seminars
mailed educational packages
mass media participation
Several methodological problems, but no
significant weight reductions achieved
Therapy
Aim of weight reduction should be to
decrease morbidity 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
Dietary Therapy
Weight reducing diets that consist of
drastically altered proportions of nutrients
may be dangerous and no more effective than
more well-balanced diets
Dietary Therapy
Two main strategies have included
low-calorie diet (800 - 1500 kcal/d)
very-low-calorie diet (<800 kcal/d)
8 RCT’s/6prospective studies:
consistent pattern of initial weight loss (mean -2.6 kg)
followed by gradual weight gain
the diet should be consistent with the NCEP Step I
or Step II diet
Reducing fat alone will not produce
weight loss unless total energy intake
is also reduced
Dietary Therapy
Reduction of weight most effective during
period of supervision, but across studies a
pattern of gradual weight regain occurred in
unsupervised period
Underestimation of caloric intake welldocumented in obesity… portion size is main
problem
REFER to a Dietician!
They are much better at this intervention than we
are...
Exercise
 Increases caloric
expenditure and also may
promote dietary compliance
 intermittent exercise (high
intensity followed by low
intensity) results in greater
reduction in weight and fat
than continuous exercise of
low-medium intensity with
the same caloric
expenditure
Exercise
Most weight loss occurs because of decreased intake,
and exercise will not lead to substantially greater
weight loss over 6 months
BUT… Sustained physical activity is most helpful
in the prevention of weight regain
Intensity of exercise should be increased gradually
Example: start walking 30 min/day, 3 days per week and
build to 45 minutes of more intense walking at least 5 days
per week
Behavior Modification Therapy
Involves analyzing the meaning of eating for
a person and the circumstances in which a
person tends to eat
May be helpful
May not be
5 RCT’s, 4 prospective cohort studies
modest weight reduction (1 - 5kg) with gradual weight regain
during follow-up period
Back to the Case
He returns 3 months later
He lost 2 kg in the first month, but has since
regained 1 kg
He is now exercising 3 times per week (walks 30
minutes)
He asks you, “Look Doc, Can’t I just take a
pill to lose weight? Or should I just have that
stomach-stapling operation?”
What do you tell him?
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 brain concentrations of
catecholamines leading to decreased appetite
or increased expenditure
Examples: phenteramine, 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
Few small studies involving these agents:
Modest benefit (-3kg in small RCT involving
Mazindol) in short term; long term effectiveness
(after 1 year of F/U) has not been studied
Sympathomimetic Drugs
These drugs have only modest benefit in
promoting weight loss, and should be used
with extreme caution in patients with cardiac
disease, hypertension, or history of stroke
AMA recommendation: consider these agents as
adjunctive to dietary therapy for:
patients with BMI > 30
patients with BMI > 27 and any of
CAD, HTN, DM, Sleep apnea
CMA Periodic Health Exam:
insufficient evidence to recommend in favor of or
against
Sibutramine
Approved in Canada late 2001(but taken off
market in Italy d/t 2 CV deaths)
Drug with both catecholaminergic and serotonergic
agonist effects ---> enhances satiety, incr metab rate
modestly enhances weight loss and can help facilitate
weight loss maintenance
increases in blood pressure and heart rate with use
Contraindicated in patients with CAD, HTN, CHF, stroke
 2 small RCTs (1 year F/U) - suggest modest weight loss
(mean 5.2 kg in one trial) but high drop-out rates (up to 44%)
Sibutramine
Risk:benefit & Cost:benefit profile must be
discussed before prescribing
Check HR, BP before Rx, q2/52 X 3/12 then
q1-3/12
Consider D/C ing Rx IF HR incr 10 beats/min
or BP incr 10 mm Hg (either syst or diast) in 2
consecutive visits.
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)
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%
Orlistat
JAMA 1999 - RCT of 1187 patients
at 1 year: -8.8 kg (orlistat) vs - 5.8kg
again, weight regain when orlistat stopped
45% completed 2 year trial
Reduction in LDL also seen (mean -0.22 mmol)
adverse event rate and profile similar to previous Lancet
trial
Bottom Line: Orlistat may result in weight
loss, but…
weight regain may occur once it is stopped
bothersome GI effects are likely to be unacceptable to
many patients
Surgery
Bariatric or weight-reduction surgery
gastric bypass (complete gastric partitioning with
anastomosis of proximal gastric segment to a
jejunal loop)
gastroplasty (partial gastric partitioning at the
proximal gastric segment with placement of a
gastric outlet stoma of fixed diameter)
Both methods intended to create an upper gastric
pouch that reduces gastric luminal capacity and
causes 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 a low-calorie diet
exercise (especially to help prevent weight regain)
Pharmacologic therapy provides only modest
benefit, and often has unacceptable side effects
 Dexfenfluramine and fenfluramine are no longer available because of
risk of severe adverse events
 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 may be effective for some patients, but should be
reserved for patients with severe obesity (BMI > 40) in whom other
strategies fail
Summary
CMA Periodic Health Exam:
a) community-based obesity prevention methods
are ineffective
b) obesity treatment methods are ineffective over
the long term (beyond 2 years) except
in small proportion of people who receive dietary or
surgical treatments
in patients with selected obesity-related diseases
weight loss may reduce need for drug therapy for the
related diseases
c) insufficient evidence to recommend in favor of
our against inclusion of BMI as part of periodic
health exam
Back to the Case
You decide with your patient to embark on a
trial of orlistat
Initially, he finds the flatulence he develops to be
quite bothersome (no oily stools!), but over time
learns that this can be minimized by avoiding
foods which are high in fat-content
At the next 3 month follow-up appointment he
has been successful at maintaining his low-calorie
diet and exercise regimen, and he reports with
great pride that he has lost a further 3 kg!
The End