ObesityThe 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;346:591-602Willett 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 managementHe states that he has been overweight for most of

his lifeHe lives by himself, and eats mostly pre-made

mealsHe works as a long-haul truck driver, and

exercises infrequently

The Case

PMHappendectomyinguinal hernia repair

Family HistoryFather - MI age 54Older brother - DM 2Both 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 12Cardiac Exam

JVP 3 cmnormal 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?

NEJM, Aug. 7, 1997

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

from NEJM, Aug. 7, 1997

Complex Interactions which Determine Relationship Between Energy Intake and Expenditure

Nature versus Nurture

Studies in twins suggest as much as 80% of variance in BMI is attributable to genetic factorsCertain 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 classsecular trend toward increasing obesity

Diagnosis and Definitions

Body Mass Index = weight (kg)

height (m)2

Greater reproducibility than skinfold thickness indicesCannot 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 > 27morbid obesity defined as BMI > 35

American Medical Association, 1998 Expert Panel on Obesityoverweight defined as BMI between 25 and 29.9obesity defined as BMI > 30

Scope of the ProblemObesity 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

HypertensionDiabetes MellitusHyperlipidemiaCoronary Artery

DiseaseObstructive Sleep

Apnea

MalignanciesBreastUterusProstateColon

Psychological Disordersdepressionanorexia nervosabulimia

The Evidence for Mortality

Annals Int Med 2003 ArticleFramingham Data

Signif decreases in Life Expectancy40 y.o. Non-smoker Smoker

Overweight female 3.3 y 7.2 y

Overweight male 3.1 y 6.7 y

Obese female 7.1 y 13.3 y

Obese male 5.8 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 differencesFor any degree of overweight, younger adults had

greater YLL than older20-30 yo w.m. BMI>45 = 13 YLL (22%20-30 yo w.f. BMI>45 = 8 YLL

Prevention

Several studies of community-based interventionsseminarsmailed educational packagesmass media participation

Several methodological problems, but no significant weight reductions achieved

TherapyAim of weight reduction should be to

decrease morbidity rather than meet cosmetic standards of thinness

Set reasonable short-term goalsRecognize that any lifestyle alterations will

need to be continued indefinitely if lower body weight is to be maintained2/3 of persons who lose weight will regain it within one

yearalmost all persons who lose weight will regain it within

5 years

Goals

Initial goal - reduce body weight by 10% within ~ 6 monthsFor 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 TherapyTwo 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 well-documented 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 graduallyExample: 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 eatMay be helpfulMay not be

5 RCT’s, 4 prospective cohort studiesmodest weight reduction (1 - 5kg) with gradual weight regain

during follow-up period

Back to the Case

He returns 3 months laterHe lost 2 kg in the first month, but has since

regained 1 kgHe 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 fenfluramineserotonin-reuptake inhibitorseffective as appetite suppressantsresult 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 diseaseprimary pulmonary hypertension

Sympathomimetic DrugsIncrease brain concentrations of catecholamines

leading to decreased appetite or increased expenditureExamples: phenteramine, mazindolphenylpropanolamine removed from OTC market by FDA after

recent demonstration of risk of hemorrhagic strokeunsuitable 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 DrugsThese 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 strokeAMA recommendation: consider these agents as

adjunctive to dietary therapy for:patients with BMI > 30patients 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 ratemodestly enhances weight loss and can help facilitate

weight loss maintenance increases in blood pressure and heart rate with useContraindicated 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 metabolisminhibits pancreatic lipases resulting in incomplete

breakdown of ingested fatfecal fat excretion increased (peaks at ~30% of

ingested fat)

Orlistat

Lancet 1998 - RCT, 743 patients, 2 yearsat 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 - 5.8kgagain, weight regain when orlistat stopped45% completed 2 year trialReduction 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 stoppedbothersome GI effects are likely to be unacceptable to

many patients

Surgery

Bariatric or weight-reduction surgerygastric 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 studylong-term success in sustaining initial weight

reduction which occurred in first 3-6 monthsmagnitude of weight loss greater than that

observed with dietary/drug treatmentsPost-operative mortality low (1 death in 707

patients)Perioperative morbidity < 5%

Surgical Interventions

Reserved for patientsin whom efforts at medical therapy have failedwho 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 desirableto help control diseases worsened by obesity

(diabetes, coronary artery disease, etc.)to help decrease the likelihood of developing the

associated diseases

SummaryThe initial strategy should include

dietary therapy with a low-calorie dietexercise (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

SummaryCMA Periodic Health Exam:

a) community-based obesity prevention methods are ineffective

b) obesity treatment methods are ineffective over the long term (beyond 2 years) exceptin small proportion of people who receive dietary or

surgical treatmentsin 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 orlistatInitially, 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