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 Supplement to

THE AMERICAN
JOURNAL of April 2009

MEDICINE
Volume 122
Number 4A

The Green Journal

The Obesity Epidemic: Strategies in

Reducing Cardiometabolic Risk
GUEST EDITORS:
Louis J. Aronne, MD
Clinical Professor of Medicine
Weill Cornell Medical College
Director
The Comprehensive Weight Control Program
New York-Presbyterian Hospital
New York, New York

Stephen Havas, MD, MPH, MS

Former Vice President
Science, Quality, and Public Health
American Medical Association
Chicago, Illinois

CME ISSUE
OFFICIAL JOURNAL OF

Full Text Available

Online to Subscribers at:
www.amjmed.com
ISSN 0002-9343
THE AMERICAN
JOURNAL of
MEDICINE
April 2009
Volume 122
® Number 4A

The Obesity Epidemic: Strategies in Reducing

Cardiometabolic Risk
GUEST EDITORS
Louis J. Aronne, MD
Clinical Professor of Medicine
Weill Cornell Medical College
Director
The Comprehensive Weight Control Program
New York-Presbyterian Hospital
New York, New York
Stephen Havas, MD, MPH, MS
Former Vice President
Science, Quality, and Public Health
American Medical Association
Chicago, Illinois

This supplement is supported by an educational grant from sanofi-aventis Pharmaceuticals, Inc. Editorial support by IMED
Communications, Califon, New Jersey.

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THE AMERICAN
JOURNAL of
MEDICINE
April 2009
Volume 122
® Number 4A

The Obesity Epidemic: Strategies in Reducing

Cardiometabolic Risk

S1 Introduction
Stephen Havas, Louis J. Aronne, and Kristina A. Woodworth

S4 Obesity: Why Be Concerned?

W. Virgil Brown, Ken Fujioka, Peter W. F. Wilson, and Kristina A. Woodworth

S12 Regulation of Energy Homeostasis and Health Consequences in Obesity

Judith Korner, Stephen C. Woods, and Kristina A. Woodworth

S19 Obesity Prevention: Recommended Strategies and Challenges

Anne M. Wolf and Kristina A. Woodworth

S24 When Prevention Fails: Obesity Treatment Strategies

Louis J. Aronne, Thomas Wadden, Kathy Keenan Isoldi, and Kristina A. Woodworth

S33 An Obesity/Cardiometabolic Risk Reduction Disease Management Program:

A Population-Based Approach
Victor G. Villagra

S41 CME Section

The Obesity Epidemic: Strategies in Reducing Cardiometabolic Risk
Guest Editors
Louis J. Aronne, MD
Clinical Professor of Medicine
Weill Cornell Medical College
Director
The Comprehensive Weight Control Program
New York-Presbyterian Hospital
New York, New York
Faculty
W. Virgil Brown, MD
Charles Howard Candler Professor
Emory University School of Medicine
Atlanta, Georgia
Ken Fujioka, MD
Director, Nutrition and Metabolic Research
Director, Center for Weight Management
Scripps Clinic
San Diego, California
Kathy Keenan Isoldi, MS, RD, CDE
Coordinator, Clinical Nutrition Services
The Comprehensive Weight Control Program
New York-Presbyterian Hospital
New York, New York
Judith Korner, MD, PhD
Assistant Professor of Clinical Medicine
Columbia University
Director, Weight Control Center
Columbia University Medical Center
New York, New York
Bruce S. Pyenson, FSA, MAAA
Member of the Healthcare Financial
Management Association
Principal and Consulting Actuary
Milliam Consultants and Actuaries
New York, New York
Stephen Havas, MD, MPH, MS
Former Vice President, Science, Quality, and Public
Health
American Medical Association
Chicago, Illinois
Victor G. Villagra, MD
Assistant Clinical Professor
Department of Medicine
University of Connecticut
President, Health & Technology Vector, Inc.
Farmington, Connecticut
Thomas A. Wadden, PhD
Professor of Psychology
University of Pennsylvania School of Medicine
Director, Center for Weight and Eating Disorders
University of Pennsylvania
Philadelphia, Pennsylvania
Peter W. F. Wilson, MD
Professor of Medicine
Emory University School of Medicine
Atlanta, Georgia
Anne M. Wolf, RD, MS
Instructor of Research
University of Virginia School of Medicine
Charlottesville, Virginia
Stephen C. Woods, PhD
Professor of Psychiatry
Director, Obesity Research Center
University of Cincinnati
Cincinnati, Ohio
Discussants

Earl S. Ford, MD, MPH Mark S. Johnson, MD, MPH

Medical Officer New Jersey Chapter of the American
Centers for Disease Control and Prevention Academy of Family Physicians
Atlanta, Georgia Chairman and Professor of Family Medicine
UMDNJ-New Jersey Medical School
William Griffith Newark, New Jersey
Director of Marketing
National Minority Health Month Foundation
Washington, DC Wahida Karmally, DrPH, RD, CDE
American Dietetic Association
Van S. Hubbard, MD, PhD Associate Research Scientist and Director of Nutrition
Rear Admiral, US Public Health Service Irving Center for Clinical Research
Director, NIH Division of Nutritional Research Columbia University
Coordination
New York, New York
National Institutes of Health
Senior Advisor to the Secretary on Obesity
Department of Health and Human Services
Bethesda, Maryland

Medical Writer

Kristina A. Woodworth
SciMantis Communications, Inc.
Pen Argyl, Pennsylvania
Faculty Disclosures
Faculty are expected to disclose to the program audience any real or apparent conflict(s) of interest related to the
content of their presentation(s).

The information presented represents the views and opinions of the individual authors and does not constitute the
opinion or endorsement of, or promotion by, the American Medical Association, IMED Communications, or sanofi-
aventis Pharmaceuticals, Inc. Reasonable efforts have been made to present educational subject matter in a bal-
anced, unbiased fashion and in compliance with regulatory requirements. The participant must always use his or her
own personal and professional judgment when considering further application of this information, particularly as it
may relate to patient diagnostic or treatment decisions including, without limitation, US Food and Drug Administra-
tion–approved uses and any off-label uses.

Louis J. Aronne, MD, has received financial support for research from Amylin Pharmaceuticals, Inc, GlaxoSmithKline,
Medtronic, Inc, Merck & Co, Inc, Obecure Ltd, Orexigen Therapeutics, Inc, Pfizer Inc, sanofi-aventis Pharmaceuticals, Inc,
and Transneuronix, Inc; is a consultant for Manhattan Pharmaceuticals, Inc, Metabolic Therapeutics, Inc, and sanofi-aventis
Pharmaceuticals, Inc; is a member of a Speakers’ Bureau for Pfizer Inc and sanofi-aventis Pharmaceuticals, Inc; and has
received grant support or consulted for Arena Pharmaceuticals, Inc, GI Dynamics, Johnson & Johnson, Novo Nordisk,
TransTech Pharma, Inc, and Vivus Inc.

W. Virgil Brown, MD, is a consultant for Abbott Laboratories, AstraZeneca, AtherGenics, Inc, Bayer, Bristol-Myers Squibb
Company, Merck & Co, Inc, Pfizer Inc, Reliant Pharmaceuticals, Inc, Daiichi Sankyo Co, Ltd, and Schering-Plough
Corporation; is a speaker and advisory committee member for Abbott Laboratories, AstraZeneca, Merck & Co, Inc, Pfizer Inc,
and Schering-Plough Corporation; and has received grant research support from Abbott Laboratories, AstraZeneca, Eli Lilly
and Company, Kos Pharmaceuticals, Inc, Merck & Co, Inc, Pfizer Inc, Schering-Plough Corporation, and Takeda Pharma-
ceuticals North America, Inc.

Earl S. Ford, MD, MPH, has no relevant financial relationships with a commercial entity producing healthcare-related
products and/or services.

Ken Fujioka, MD, has disclosed that the commercial entities with which he has relationships do not produce healthcare-
related products or services relevant to the content he is planning, developing, or presenting for this activity.

William Griffith has no relevant financial relationships with a commercial entity producing healthcare-related products and/or
services.

Stephen Havas, MD, MPH, MS, has no relevant financial relationships with a commercial entity producing healthcare-
related products and/or services.

Van S. Hubbard, MD, PhD, has no relevant financial relationships with a commercial entity producing healthcare-related
products and/or services.

Kathy Keenan Isoldi, MS, RD, CDE, has no relevant financial relationships with a commercial entity producing healthcare-
related products and/or services.

Mark S. Johnson, MD, MPH, has no relevant financial relationships with a commercial entity producing healthcare-related
products and/or services.

Wahida Karmally, DrPH, RD, CDE, has no relevant financial relationships with a commercial entity producing healthcare-
related products and/or services.

Judith Korner, MD, PhD, is a consultant for GlaxoSmithKline and a paid speaker for Merck & Co, Inc, and sanofi-aventis
Pharmaceuticals, Inc.
Bruce S. Pyenson, FSA, MAAA, is a consultant for Amylin Pharmaceuticals, Inc, APS Healthcare, Inc, GlaxoSmithKline,
Matria Healthcare, Novartis, Pfizer Inc, and numerous insurers, employers, and health maintenance organizations.

Victor G. Villagra, MD, is a member of the Board of Directors of Genomas Inc, a consultant for Healthways, Inc, and
sanofi-aventis Pharmaceuticals, Inc, and an independent contractor for the Disease Management Association of America.

Thomas A. Wadden, PhD, is a consultant for Abbott Laboratories.

Peter W. F. Wilson, MD, has received grant support from GlaxoSmithKline, sanofi-aventis Pharmaceuticals, Inc, and Wyeth.

Anne M. Wolf, RD, MS, has disclosed that the commercial entities with which she has relationships do not produce
healthcare-related products or services relevant to the content she is planning, developing, or presenting for this activity.

Stephen C. Woods, PhD, is a consultant and paid speaker for sanofi-aventis Pharmaceuticals, Inc.

Kristina A. Woodworth has no relevant financial relationships with a commercial entity producing healthcare-related
products and/or services.
 CME INFORMATION
The Obesity Epidemic: Strategies in Reducing
Cardiometabolic Risk
Target Audience
Primary care physicians

Educational Objectives
Upon completion of this activity, the participant should be able to:
● Describe the impact of obesity on public health, resource utilization, healthcare expenditures and mortality risk, and quality
of life.
● Recognize the role of adipose tissue as an endocrine organ and the effect that alterations in energy homeostasis may have
on fat storage and function.
● Discuss the endogenous endocannabinoid system and its effect on energy balance, fat storage, and the adipose endocrine
system.
● Identify effective strategies at the disposal of primary care clinicians for recognizing patients at risk of cardiovascular and
metabolic disease.
● Specify current and future options, including behavioral and pharmacologic strategies, to reduce risk factors for cardiovascular
and metabolic disease in the community setting.

Accreditation Statement
The American Medical Association is accredited by the Accreditation Council for Continuing Medical Education to provide
continuing medical education for physicians.

Designation Statement
The American Medical Association designates this educational activity for a maximum of 4.0 AMA PRA Category 1
Credits™. Physicians should only claim credit commensurate with the extent of their participation in the activity.
To receive AMA PRA Category 1 Credits™ for your participation in this educational activity, you must read the supplement
and complete both the posttest and the evaluation form.

Release Date: April 2009

Expiration Date: No credit will be given after April 30, 2010
Supplement issue
Introduction
The problem of obesity in the United States has become
increasingly prominent and is now recognized as a critical
target for public health intervention. Obesity rates have
increased from 13.4% of the American population in 1960
to 30.9% in 2000.1 Although the actual number of over-
weight or obese individuals in the United States has been
debated, one analysis estimates that 66% of Americans are
overweight or obese (body mass index [BMI] ⱖ25).2 Public
health advocates are now beginning to signal a call to
action. For example, the Robert Wood Johnson Foundation
is devoting $500 million in funds to combat childhood
obesity and its potential for lasting impact in adults of the
next generation, with a goal of reversing the obesity epi-
demic in American children by 2015.3
A multidisciplinary panel of experts with experience in
cardiometabolic risk convened recently to review the evolv-
ing literature; discuss current clinical practice issues as they
relate to diagnosis, treatment, and prevention; and evaluate
new options for treatment of obesity. Select faculty elected
to develop articles based on these discussions with the intent
of providing clinicians with valuable information to make
informed decisions within their practice. These contribu-
tions form the basis for the articles in this supplement to The
American Journal of Medicine.
In the first article, Dr. W. Virgil Brown and colleagues
highlight the seriousness of the obesity epidemic by exam-
ining the wide array of health risks that can accompany
overweight and obesity, potentially leading to mortality and
morbidity. Obesity can have detrimental health effects on
almost every major organ system, the most prominent im-
pact being the increased risk for cardiovascular disease and
type 2 diabetes mellitus related to hypertension, dyslipide-
mia, and insulin resistance.4 Moreover, obesity has been
linked to an increased risk for certain cancers in both men
and women.5,6 The increased morbidity and early mortality
from these health risks can have a far-reaching impact on
the healthcare system in terms of resources and costs. The
potential for early mortality from obesity was made strik-
Statement of author disclosure: Please see the Author Disclosures
section at the end of this article.
Requests for reprints should be addressed to Louis J. Aronne, MD,
Weill Cornell Medical College, Comprehensive Weight Control Program,
New York-Presbyterian Hospital, 1165 York Avenue, New York, New
York 10028.
E-mail address: ljaronne@med.cornell.edu
0002-9343/$ -see front matter © 2009 Published by Elsevier Inc.
doi:10.1016/j.amjmed.2009.01.001
ingly clear in an analysis concluding that the gains in life
expectancy achieved in the US population during the 20th
century could level off or decline if current obesity rates are
not reversed.7
Concern exists that the correlations between BMI, an
indirect measure of overweight and obesity, and certain
health outcomes, particularly mortality, have been incon-
sistent. However, the inconsistencies may reflect, in part,
inadequate control of confounding variables or improved
treatment of comorbid conditions in overweight and
obese individuals. In addition, risk of adverse health
outcomes associated with both BMI and waist circumfer-
ence, including mortality, varies with age, sex, race/
ethnicity, and socioeconomic status, and may reflect pop-
ulation-specific differences in body composition, fat
distribution, causes of overweight, and genetic suscepti-
bility. Although BMI remains a useful screening tool to
assess a patient’s overall disease risk in association with
weight, clinicians should recognize that additional as-
sessment tools, including waist circumference and waist-
to-hip ratio, are available to help develop a better picture
of global health risk in patients evaluated for overweight
and obesity. It is critical to understand that the available
obesity assessment tools are indirect measures of body
fatness, as reflected by the continuing controversy in
identifying the best instrument to predict different health
risks related to excess weight. Ultimately, clinicians
should take into account an individual’s global health and
lifestyle, including the presence of other diseases, other
disease risk factors, and family history, when considering
a person’s overall disease risk.
As discussed in the second article, by Dr. Judith Korner
and colleagues, the importance of obesity as a medical
issue, and not just a matter of cosmetics or lifestyle choice,
has resulted in a research impetus to identify the underlying
mechanisms of energy homeostasis and obesity. These in-
vestigations have uncovered important neuroendocrine
pathways that regulate food intake at each meal, energy
expenditure, and fat storage. An important finding in these
investigations has been the endocrine function of adipose
tissue in releasing hormones that regulate energy homeosta-
sis.8-10 Moreover, detrimental inflammatory endocrine ef-
fects of adipose tissue are accentuated in obesity, which is
likely a contributing factor to the cardiometabolic risk dem-
onstrated with excess body weight.11-15
S2
Large-scale prevention strategies have been proposed in
light of the current obesity epidemic. Systematic reviews
performed by an independent Task Force on Community
Preventive Services that are summarized in the Centers for
Disease Control and Prevention’s (CDC) Guide to Commu-
nity Preventive Services stress that available literature sup-
ports the value of school-based and workplace interventions
to combat obesity, such as providing nutritional counseling
and opportunities for exercise.16,17 Nevertheless, current
obesity prevention efforts are often undermined by a toxic
food environment of convenience food portions that have
been increasing in size, a higher percentage of meals eaten
outside of the home, a high consumption of sugar-based
drinks, and higher levels of dietary sodium in the diet that
increase thirst and the consumption of these high-calorie
drinks.18-21 Dietitian Anne M. Wolf and Kristina A. Wood-
worth present a review of strategies for obesity prevention,
including the need for more effective community-wide in-
tervention programs.
Effective prevention and treatment strategies are clearly
needed to stem the tide of potential health complications
related to the obesity epidemic. Although lifestyle interven-
tions, behavioral therapy, and pharmacotherapy have all
demonstrated the ability to achieve the modest weight loss
that can mitigate many of the health risks of obesity,22,23
long-term weight maintenance is still elusive for many in-
dividuals. New pharmacotherapeutic strategies are being
assessed for their ability to contribute to lasting weight loss
in obesity. As discussed in the fourth article, by Dr. Louis
J. Aronne and coworkers, a combination approach that
incorporates all of these interventions may be the most
successful available approach to long-term weight loss in
obesity.24,25 Current efforts to highlight the health risks of
obesity should emphasize the importance of making these
treatment strategies more accessible to a greater number of
individuals affected by obesity.
In the final article, Dr. Victor G. Villagra explains how
designing comprehensive obesity and cardiometabolic risk
reduction disease management programs using a chronic
care model can overcome individual and healthcare system
barriers, resulting in a wider adoption of evidence-based
treatments.
Because clinicians encounter higher rates of overweight and
obesity in daily practice, the increased risks of excessive body
weight and the beneficial health effects of even modest de-
creases in weight mitigating these risks must be brought to the
forefront of medical care. Obesity must be recognized as a
critical health issue. It is hoped that the topics addressed in this
supplement will assist clinicians and other health professionals
by highlighting some of the most important current issues in
obesity and lifelong healthy weight management.
Stephen Havas, MD, MPH, MS
Formerly with the Division of Science, Quality,
and Public Health
American Medical Association
Chicago, Illinois, USA
The American Journal of Medicine, Vol 122, No 4A, April 2009
Louis J. Aronne, MD
Department of Medicine
Weill Cornell Medical College
The Comprehensive Weight Control Program
New York-Presbyterian Hospital
New York, New York, USA
Kristina A. Woodworth
SciMantis Communications, Inc
Pen Argyl, Pennsylvania, USA
AUTHOR DISCLOSURES
The authors who contributed to this article have disclosed
the following industry relationships:
Stephen Havas, MD, MPH, MS, has no relevant financial
relationships with a commercial entity producing health-
care-related products and/or services.
Louis J. Aronne, MD, has received financial support for
research from Amylin Pharmaceuticals, Inc, GlaxoSmith-
Kline, Medtronic, Inc, Merck & Co, Inc, Obecure Ltd,
Orexigen Therapeutics, Inc, Pfizer Inc, sanofi-aventis Phar-
maceuticals, Inc, and Transneuronix, Inc; is a consultant
for Manhattan Pharmaceuticals, Inc, Metabolic Therapeu-
tics, Inc, and sanofi-aventis Pharmaceuticals, Inc; is a
member of a Speakers’ Bureau for Pfizer Inc and sanofi-
aventis Pharmaceuticals Inc; and has received grant sup-
port or consulted for Arena Pharmaceuticals, Inc, GI Dy-
namics, Johnson & Johnson, Novo Nordisk, TransTech
Pharma, Inc, and Vivus Inc.
Kristina A. Woodworth has no relevant financial relation-
ships with a commercial entity producing healthcare-
related products and/or services.
References
1. Flegal KM, Carroll MD, Ogden CL, Johnson CL. Prevalence and trends in
obesity among US adults, 1999-2000. JAMA. 2002;288:1723-1727.
2. Ogden CL, Carroll MD, Curtin LR, McDowell MA, Tabak CJ, Flegal
KM. Prevalence of overweight and obesity in the United States, 1999-
2004. JAMA. 2006;295:1549-1555.
3. Robert Wood Johnson Foundation Announces $500-Million Commit-
ment to Reverse Childhood Obesity in US [press release]. Princeton,
NJ: Robert Wood Johnson Foundation, April 4, 2007. Available at:
http://www.rwjf.org/newsroom/product.jsp?id⫽21938. Accessed De-
cember 14, 2008.
4. National Heart, Lung, and Blood Institute (NHLBI). The Practical
Guide: Identification, Evaluation, and Treatment of Overweight and
Obesity in Adults. Bethesda, MD: National Heart, Lung, and Blood
Institute, National Institutes of Health, Dept of Health and Human
Services, October 2000. NIH Publication No. 00-4084.
5. Calle EE, Rodriguez C, Walker-Thurmond K, Thun MJ. Overweight,
obesity, and mortality from cancer in a prospectively studied cohort of
US adults. N Engl J Med. 2003;348:1625-1638.
6. Lukanova A, Bjor O, Kaaks R, et al. Body mass index and cancer:
results from the Northern Sweden Health and Disease Cohort. Int J
Cancer. 2006;118:458-466.
7. Olshansky SJ, Passaro DJ, Hershow RC, et al. A potential decline in
life expectancy in the United States in the 21st century. N Engl J Med.
2005;352:1138-1145.
8. Schwartz MW, Woods SC, Porte D Jr, Seeley RJ, Baskin DG. Central
nervous system control of food intake. Nature. 2000;404:661-671.
Havas et al The Obesity Epidemic
9. Marx J. Cellular warriors at the battle of the bulge. Science. 2003;299:
846-849.
10. Korner J, Aronne LJ. The emerging science of body weight regulation
and its impact on obesity treatment. J Clin Invest. 2003;111:565-570.
11. Marette A. Mediators of cytokine-induced insulin resistance in obesity
and other inflammatory settings. Curr Opin Clin Nutr Metab Care.
2002;5:377-383.
12. Lyon CJ, Law RE, Hsueh WA. Minireview: adiposity, inflammation,
and atherogenesis. Endocrinology. 2003;144:2195-2200.
13. Trayhurn P, Wood IS. Adipokines: inflammation and the pleiotropic
role of white adipose tissue. Br J Nutr. 2004;92:347-355.
14. Steinberg HO, Baron AD. Vascular function, insulin resistance and
fatty acids. Diabetologia. 2002;45:623-634.
15. Caballero AE. Endothelial dysfunction in obesity and insulin resistance: a
road to diabetes and heart disease. Obes Res. 2003;11:1278-1289.
16. Centers for Disease Control and Prevention (CDC). Guide to Commu-
nity Preventive Services (Community Guide). [CDC Website.] Avail-
able at: http://www.thecommunityguide.org/obese/default.htm. Ac-
cessed April 10, 2007.
17. Katz DL, O’Connell M, Yeh MC, et al, for the Task Force on Com-
munity Preventive Services. Public health strategies for preventing and
controlling overweight and obesity in school and worksite settings.
MMWR Recomm Rep. 2005;54:1-12. Available at: http://www.cdc.gov/
mmwr/preview/mmwrhtml/rr5410a1.htm. Accessed April 20, 2007.
S3
18. Rolls BJ, Morris EL, Roe LS. Portion size of food affects energy
intake in normal-weight and overweight men and women. Am J Clin
Nutr. 2002;76:1207-1213.
19. Rolls BJ, Kim S, Fedoroff IC. Effects of drinks sweetened with
sucrose or aspartame on hunger, thirst and food intake in men. Physiol
Behav. 1990;48:19-26.
20. McCrory MA, Fuss PJ, Hays NP, Vinken AG, Greenberg AS, Roberts
SB. Overeating in America: association between restaurant food con-
sumption and body fatness in healthy adult men and women ages 19 to
80. Obes Res. 1999;7:564-571.
21. Karppanen H, Mervaala E. Sodium intake and hypertension. Prog
Cardiovasc Dis. 2006;49:59-75.
22. Knowler WC, Barrett-Connor E, Fowler SE, et al. Reduction in the
incidence of type 2 diabetes with lifestyle intervention or metformin.
N Engl J Med. 2002;346:393-403.
23. Tuomilehto J, Lindstrom J, Eriksson JG, et al, for the Finnish Diabetes
Prevention Study Group. Prevention of type 2 diabetes mellitus by
changes in lifestyle among subjects with impaired glucose tolerance.
N Engl J Med. 2001;344:1343-1350.
24. Wadden TA, Berkowitz RI, Womble LG, et al. Randomized trial of
lifestyle modification and pharmacotherapy for obesity. N Engl J Med.
2005;353:2111-2120.
25. Wadden TA, Berkowitz RI, Sarwer DB, Prus-Wisniewski R, Steinberg
C. Benefits of lifestyle modification in the pharmacologic treatment of
obesity: a randomized trial. Arch Intern Med. 2001;161:218-227.
Supplement issue

Obesity: Why Be Concerned?

W. Virgil Brown, MD,a Ken Fujioka, MD,b Peter W. F. Wilson, MD,a Kristina A. Woodworthc
a
Department of Internal Medicine, Emory University School of Medicine, Atlanta, Georgia, USA; bCenter for Weight Management,
Scripps Clinic, San Diego, California, USA; cSciMantis Communications, Inc, Pen Argyl, Pennsylvania, USA

ABSTRACT

The obesity epidemic in the United States represents a critical public health issue that has the potential to
incur major healthcare costs because of the substantial risks associated with excess body fat. Whereas
many recognize the significant risk of cardiovascular disease and diabetes mellitus associated with excess
body fat, a myriad of other health problems can accompany overweight and obesity, potentially leading to
early morbidity and mortality. Public recognition of obesity as an important health crisis, and not simply
a matter of cosmetics or lifestyle choice, is clearly needed. A greater awareness of the health risks
associated with excess weight will facilitate more frequent obesity screenings and discussions about
healthy weight management that have the potential to result in a greater commitment of healthcare
resources to effective obesity prevention and management strategies.
© 2009 Published by Elsevier Inc. • The American Journal of Medicine (2009) 122, S4 –S11

KEYWORDS: Cardiovascular disease; Health care costs; Lipoproteins; Metabolic syndrome; Obesity; Risk factor

Obesity is a problem that has reached epidemic proportions
in the United States. Data from the National Health Exam-
ination Survey (NHES) and the National Health and Nutri-
tion Examination Survey (NHANES) demonstrated a steady
increase in obesity rates over the second half of the 20th
century. It is now estimated that ⬎66% of the US adult pop-
ulation is overweight or obese (body mass index [BMI] ⱖ25).1
An analysis reported by Olshansky and associates2 pro-
jected a reversal of 20th-century gains in American life
expectancy owing to the health consequences of the obesity
epidemic; these findings highlight the critical importance of
addressing overweight and obesity, including the associated
health risks, from the perspectives of public education and
policy. In an effort to prompt a greater level of commitment
to healthy weight management, this review discusses the
substantial health concerns that present with excess body
fat.
DEFINING OBESITY
BMI is commonly accepted as a general measure of over-
weight and obesity. It is calculated by dividing the patient’s
Statement of author disclosure: Please see the Author Disclosures
section at the end of this article.
Requests for reprints should be addressed to W. Virgil Brown, MD,
Emory University School of Medicine, Atlanta VAMC 111, 1670 Clair-
mont Road, Atlanta, Georgia 30033.
E-mail address: W.Virgil.Brown@med.va.gov.
weight in kilograms by the square of the individual’s height
in meters. Adults with a BMI in the range of 25 to 29.9 are
classified as overweight, and those with a BMI of ⱖ30 are
classified as obese.3 The location of excess body fat is also
a factor in the detrimental effects of obesity. Intra-abdom-
inal fat is more closely associated with diabetes mellitus and
vascular disease. Therefore, measurements of waist size
have been used to predict the extent of excess risk with body
fat.
THE METABOLIC SYNDROME AND OBESITY
In defining the metabolic syndrome, the National Choles-
terol Education Program Adult Treatment Panel III (NCEP
ATP III) recognized elevated waist circumference, or ab-
dominal obesity, as an independent component of the syn-
drome along with elevated triglyceride concentrations, low
high-density lipoprotein (HDL) cholesterol levels, elevated
blood pressure, and high fasting glucose concentrations
(Table 1).4 Individuals with ⱖ3 of these factors are classi-
fied as having the metabolic syndrome.4 A joint statement
by the American Heart Association (AHA) and the Na-
tional Heart, Lung, and Blood Institute (NHLBI) concurs
with this definition but lowers the threshold for elevated
fasting glucose concentrations from 110 mg/dL to 100 mg/dL
(1 mg/dL ⫽ 0.05551 mmol/L), because of the importance of
this marker in assessing diabetic risk.5 With the 2001 update
in recommendations, NCEP ATP III emphasized the impor-

0002-9343/$ -see front matter © 2009 Published by Elsevier Inc.

doi:10.1016/j.amjmed.2009.01.002
Brown et al Obesity and Health Concerns
Table 1 Clinical Components of the Metabolic Syndrome as
Defined by the National Cholesterol Education Program Adult
Treatment Panel III (NCEP ATP III)
Risk Factor Defining Level
Abdominal obesity (waist circumference)
Men ⬎102 cm (⬎40 in)
Women ⬎88 cm (⬎35 in)
Triglycerides* ⱖ150 mg/dL
HDL cholesterol†
Men ⬍40 mg/dL
Women ⬍50 mg/dL
Blood pressure ⱖ130/ⱖ85 mm Hg
Fasting glucose ⱖ110 mg/dL‡
HDL ⫽ high-density lipoprotein.
*1 mg/dL ⫽ 0.01129 mmol/L.
†
1 mg/dL ⫽ 0.02586 mmol/L.
‡
The American Heart Association/National Heart, Lung, and Blood In-
stitute (AHA/NHLBI) lowered this threshold to ⱖ100 mg/dL (1 mg/dL ⫽
0.05551 mmol/L).
Adapted with permission from JAMA.4
tance of focusing on multiple risk factors in mitigating the
substantial health consequences associated with the meta-
bolic syndrome and suggested that clinicians consider the
metabolic syndrome as a secondary target for risk-reduction
therapy after the management of low-density lipoprotein
(LDL) cholesterol, because of the substantial disease burden
associated with the syndrome.4 Furthermore, the NCEP
ATP III recommended weight reduction and increased
physical activity as a strategy to treat all of the factors that
define the metabolic syndrome.4
The cluster of cardiometabolic factors referred to as the
metabolic syndrome substantially increases the risk of im-
portant health consequences, including heart attack, stroke,
and type 2 diabetes, all of which can result in morbidity and
early mortality. Data from NHANES III (1988 to 1994)
revealed that in Americans ⱖ50 years of age, the age-
adjusted prevalence of coronary heart disease (CHD) was
19.2% in those with the metabolic syndrome and diabetes
compared with 8.7% in those without the metabolic syn-
drome or diabetes.6 Diabetes substantially increased the rate
of CHD in individuals with the metabolic syndrome. An
analysis from the San Antonio Heart Study reported that the
metabolic syndrome, as defined by the NCEP ATP III,
predicted both all-cause mortality and cardiovascular mor-
tality.7 Likewise, in a large population-based study of fa-
milial type 2 diabetes conducted in Finland and Sweden, the
metabolic syndrome was associated with a significant risk
for CHD, myocardial infarction, and stroke, as well as a
significant risk for both all-cause mortality and cardiovas-
cular mortality (P ⬍0.001).8
In light of the substantial risks presented by the meta-
bolic syndrome, it is critical that clinicians develop routine
strategies to control these factors in daily practice. Further-
more, the links between obesity, particularly abdominal
obesity, and the metabolic syndrome suggest that many of
S5
the factors comprising the NCEP ATP III definition are
present in patients with excess body weight. Clinicians
therefore should recognize the importance of weight control
in mitigating risk and the benefits of screening overweight
and obese patients for underlying conditions, including hy-
pertension, dyslipidemia, and type 2 diabetes.
OBESITY AND CARDIOVASCULAR DISEASE
The recognition of the association between increased
cardiovascular disease incidence and overweight and
obesity suggests that weight loss represents an important
opportunity for primary cardiovascular disease preven-
tion. An analysis from the Framingham Heart Study re-
sulted in the findings that both overweight and obesity
increased the risk of the development of cardiovascular risk
factors, including hypertension, hypercholesterolemia, and
diabetes, as well as overt cardiovascular disease.9 It is
critical to control underlying cardiovascular risk factors and
encourage weight loss in individuals presenting with over-
weight and obesity to avoid substantial long-term cardio-
vascular disease.
Mechanisms of Cardiovascular Risk
Excess weight, especially excess adipose tissue, exacerbates
a number of cardiovascular and metabolic risk factors. It is
now recognized that this increased risk is characterized by a
series of metabolic changes that alter lipid profiles and increase
the potential for atherosclerosis due to inflammation.
Adipose tissue, especially intra-abdominal visceral fat
associated with abdominal obesity, has an independent en-
docrine function that results in the release of inflammatory
adipokines, including tumor necrosis factor–␣, interleu-
kin-6, and plasminogen-activator inhibitor–1 (PAI-1).10-12
These hormones increase risk for atherosclerosis, thrombo-
sis, and diabetes. Adipokines also may affect the progres-
sion of endothelial dysfunction, which further increases
inflammation and the risk for atherosclerosis.13 Inflamma-
tory adipokines increase atherogenic potential by altering
the normal function of arterial smooth muscle cells and
white blood cells, including lymphocytes and monocytes.
The adipokine PAI-1 has a prothrombotic effect that in-
creases the risk for thromboembolic events. Inflammatory
adipokines may also increase insulin resistance and diabetes
in obesity.10-12 Free fatty acids are also produced more
readily in the visceral fat associated with abdominal obesity
and may decrease insulin sensitivity, impair vascular reac-
tivity, and increase endothelial dysfunction.13,14 Mean-
while, higher blood concentrations of adiponectin are asso-
ciated with less evidence of inflammation and improved
insulin sensitivity; however, adiponectin levels have been
shown to decrease with increasing levels of obesity and
adiponectin is counterregulated by the inflammatory
adipokines.12,13,15
Abnormal lipid metabolism, particularly the cluster of
lipid abnormalities that characterize atherogenic dyslipide-
mia, is common in individuals with obesity and type 2
S6
diabetes and increases the risk for cardiovascular events.
Individuals with obesity and the metabolic syndrome
present with increased concentrations of very-low-density
lipoprotein (VLDL) particles, increased triglycerides, and
small-particle LDL, increased LDL particle number, and
decreased HDL particle size. This has been confirmed by
measuring particle numbers through nuclear magnetic res-
onance spectral analysis.16-18 These lipoproteins can also
undergo a process of oxidation that results in the formation
of foam cells and enhanced monocyte binding that results in
the early stages of atherosclerotic plaque.19 Meanwhile,
small-particle LDL has a greater atherogenic potential and
is more common in individuals with diabetes.20 However, it
should be stressed that the total number of lipoprotein par-
ticles may be a more important factor in predicting the
potential for cardiovascular disease.21 Elevated triglyceride
concentrations are associated with greater circulating num-
bers of triglyceride-rich VLDL particles and higher levels of
VLDL cholesterol, an environment that alters the metabo-
lism of LDL and HDL cholesterol and contributes to athero-
genic potential.22 Elevated triglyceride concentration is an
important independent risk factor for atherosclerotic poten-
tial and may partly explain the inability of statin therapies
that address hypercholesterolemia in fully protecting against
cardiovascular events.23
Weight loss is associated with increases in adiponectin
levels, a reversal of inflammatory adipokine release, and
improved endothelial function.13 These findings strongly
support the importance of obesity as a risk factor for car-
diovascular disease, including atherosclerosis and thrombo-
embolic events, and highlight the value of weight loss as a
therapeutic modality.
Evidence of Cardiovascular Risk with Excess
Weight
The increased cardiovascular risk associated with over-
weight, obesity, and the metabolic syndrome is routinely
demonstrated in clinical practice. One population-based
study found that the presence of the metabolic syndrome as
defined by the NCEP and the World Health Organization
(WHO) in a cohort of middle-aged men was an accurate
predictor of cardiovascular mortality and all-cause mortal-
ity.24 This increased mortality risk was independent of other
confounding traits such as smoking, alcohol consumption,
and LDL cholesterol levels.
In a population of postmenopausal women, subjects with
NCEP-defined metabolic syndrome or a combination of
enlarged waist and elevated triglyceride concentrations
were at a significantly increased risk for cardiovascular and
all-cause mortality (P ⬍0.05).25 The authors of this study
noted that the combination of enlarged waist and elevated
triglyceride concentrations was a stronger predictor of
atherogenesis than was the metabolic syndrome and con-
cluded that the use of enlarged waist circumference and
elevated triglyceride concentrations could be a valuable,
The American Journal of Medicine, Vol 122, No 4A, April 2009
cost-savings tool to identify individuals at risk in clinical
practice.
The Framingham Heart Study, which followed ⬎5,000
individuals for a period of up to 44 years, likewise reported
substantial cardiovascular risk linked to overweight and
obesity. In one analysis, overweight and obesity were inde-
pendently associated with an increased risk for developing
cardiovascular disease as well as established cardiovascular
risk factors, including hypertension, hypercholesterolemia,
and type 2 diabetes.9 It is important to note that cardiovas-
cular risk not only was increased in obese persons but also
was elevated in overweight individuals.9 Additionally, it is
notable that another Framingham analysis found that the
Framingham Risk Score was significantly superior to met-
abolic syndrome in predicting cardiovascular risk.26 These
findings highlight the importance of healthy weight main-
tenance and the clinical value of assessing patients exhib-
iting overweight and obesity for underlying cardiovascular
disease.
OBESITY AND ENDOCRINE DISEASE
Obesity clearly increases the risk of developing type 2
diabetes. Large population studies have confirmed the links
between excess weight and the development of insulin re-
sistance and diabetes, suggesting that patients with exces-
sive weight are at substantial risk for developing diabetes.
In the Nurses’ Health Study, which followed close to
85,000 female nurses, a BMI of ⱖ25 (overweight) was the
single most important risk factor for the development of
type 2 diabetes over a 16-year period.27 The authors noted
that modifiable changes in lifestyle and health, including
maintenance of a BMI ⱕ25; consumption of a diet high in
fiber and low in fat and glycemic load; regular exercise;
avoidance of smoking; and moderate alcohol consumption
reduced the incidence of type 2 diabetes by approximately
90% compared with subjects who did not demonstrate these
factors or make these changes.
BMI, as a measure of excess weight, can be an important
predictor of developing diabetes. In fact, BMI has been
shown to correlate linearly with the risk for both CHD and
diabetes. One analysis found that BMI values ⬎30 corre-
lated directly with the risk for developing type 2 diabetes, as
well as hypertension, CHD, and gallbladder disease.28 Fur-
thermore, men with a BMI of 26 had a 4-fold higher risk
for developing type 2 diabetes than did men whose BMI
was ⬍21; women with a BMI of 26 had an 8-fold higher
risk for developing type 2 diabetes than did women
whose BMI was ⬍21.
Abdominal obesity, classified as an elevated BMI plus
elevated waist circumference (⬎102 cm [⬎40 in] in men
and ⬎88 cm [⬎35 in] in women),4 may be a more accurate
predictor of diabetic risk. The Nurses’ Health Study re-
ported that, in female subjects, measures of abdominal obe-
sity, including waist circumference and waist-to-hip ratio,
were more predictive of diabetes risk than was BMI alone.29
A study of men aged 22 to 70 examined abdominal obesity
Brown et al Obesity and Health Concerns
by analyzing abdominal adipose tissue through magnetic
resonance imaging.30 Researchers reported that body weight
was inversely proportional to insulin sensitivity but weight
alone could not fully explain the risk of developing insulin
resistance. Meanwhile, the accumulation of body fat in the
abdominal region was found to be an important contributor
to insulin resistance, as measured by both global insulin
sensitivity and hepatic insulin sensitivity.30 Clinicians
should recognize the importance of screening for diabetes as
an important component to global risk assessment in pa-
tients presenting with chronic excess weight, especially
those demonstrating abdominal obesity.
OBESITY AND HEALTHCARE COSTS
The increased cardiometabolic risks associated with obe-
sity, including cardiovascular disease and type 2 diabetes,
have important treatment implications in terms of healthcare
utilization and resulting healthcare costs. Costs attributable
to obesity in 1995 US dollars were estimated to total $99.2
billion per year, $51.64 billion of which were associated
with direct medical costs.31 Furthermore, an analysis of
healthcare costs and wages found that in populations receiv-
ing workplace healthcare benefits, the increased healthcare
costs associated with obesity are passed on to obese workers
through lower wages.32 In individuals who are overweight
or obese, effective treatment strategies are needed to either
achieve weight loss or attenuate the underlying cardiometa-
bolic risk factors that are present with excess body weight.
Researchers have found that efforts to prevent obesity
may be less costly than are the substantial costs associated
with the treatment of obesity and comorbid cardiometabolic
risk. In one analysis, the pharmaceutical treatment of obe-
sity, achieving weight loss of 8.2% to 10.6% of initial body
weight, was associated with substantial pharmaceutical cost
savings due to a reduced need for medications to treat
diabetes, hyperlipidemia, and hypertension.31 Weight loss
was maintained at 1 year with the pharmaceutical interven-
tion. Also, the achieved weight loss demonstrated the ability
to improve risk factors for cardiovascular disease, including
total cholesterol, systolic blood pressure, LDL cholesterol,
and HDL cholesterol. The pharmaceutical costs associated
with weight loss medications were more than offset by the
reduced need for medications to treat cardiometabolic risk
factors.
Lifestyle interventions that reduce weight may also re-
duce the risk of developing type 2 diabetes and the substan-
tial pharmaceutical costs associated with treatment. In a trial
conducted by the Diabetes Prevention Program (DPP) Re-
search Group, a population of individuals with elevated
fasting glucose concentrations were treated with a lifestyle
modification program with the goals of a ⱖ7% reduction in
weight and physical activity totaling ⱖ150 minutes per
week, to determine the effects of resulting weight loss on
diabetic risk.33 Over a mean follow-up period of 2.8 years,
researchers reported that individuals receiving lifestyle in-
terventions to achieve weight loss had a 58% reduced risk of
S7
developing type 2 diabetes compared with a placebo group
and a 39% reduced risk compared with a group receiving
metformin therapy to reduce diabetic risk.33 Over a mean
follow-up of 3.2 years, another study that tracked the effects
of weight-loss lifestyle interventions on the incidence of
type 2 diabetes in individuals with impaired glucose toler-
ance likewise reported a 58% reduction in type 2 diabetes
incidence with weight loss.34 Although large-scale cam-
paigns to achieve weight loss through lifestyle interventions
may be associated with substantial costs, these costs may be
attenuated by the resulting decrease in disease risk.
OTHER HEALTH EFFECTS OF OBESITY
The projected decrease in overall life expectancy if the
current obesity epidemic is not reversed2 highlights the
importance of excess weight as a public health issue. As
noted earlier, the presence of obesity and the metabolic
syndrome increases the mortality risk associated with car-
diovascular disease.7,8,24,25 In one analysis, obese, 40-year-
old individuals demonstrated life expectancies that were
reduced by 7.1 years in women and 5.8 years in men
compared with those of normal weight,35 demonstrating the
far-reaching, lifelong implications of excess body weight.
Cancer Risk
Obesity is associated with the development of certain can-
cers in both men and women. A prospective analysis of a
population of ⬎900,000 US adults who were cancer free at
baseline found that individuals with extreme obesity (BMI
ⱖ40) had a substantially higher risk of death due to cancer
(52% and 62% in men and women, respectively) than did
those of normal weight during the 16 years of follow-up.
The authors of the study concluded that of all cancer deaths
in the United States, 14% of cases in men and 20% of cases
in women ⱖ50 years of age may be attributable to over-
weight and obesity. Overall, they predicted that 90,000
cancer deaths could be avoided if all Americans could
maintain a BMI ⬍25 throughout life.36 Researchers have
cited several potential mechanisms that increase the risk of
cancer with obesity, including the higher levels of insulin
and sex hormones observed in overweight and obese indi-
viduals.36 Other physiologic factors have been cited in the
link between specific cancers and excess weight. For in-
stance, a higher incidence of gastroesophageal reflux has
been cited as a possible causative factor in the increased risk
of esophageal cancer in overweight and obesity. A higher
rate of gallstones with overweight and obesity has also been
cited as a possible causative factor in an increased risk of
gallbladder cancer with excess weight, particularly in
women.36
In men, significant positive correlations were found be-
tween BMI and rates of death due to all cancers, as well as
esophageal cancer, stomach cancer, colorectal cancer, liver
cancer, gallbladder cancer, pancreatic cancer, prostate can-
cer, kidney cancer, non-Hodgkin’s lymphoma, multiple my-
eloma, and leukemia (P ⱕ0.03).36 In women, BMI corre-
S8
lated significantly with deaths due to all cancers, as well as
colorectal cancer, liver cancer, gallbladder cancer, pancre-
atic cancer, lung cancer, breast cancer, uterine cancer, cer-
vical cancer, ovarian cancer, kidney cancer, non-Hodgkin’s
lymphoma, and multiple myeloma (P ⱕ0.001). Uterine can-
cer was most strongly associated with excess body weight.
Women may be particularly vulnerable to cancer mortality
associated with excess body weight.36
The strong association between BMI and cancer risk in
women was reported in a Swedish population study. Inves-
tigators concluded that up to 7% of cancers in the women
studied were attributable to overweight and obesity. More-
over, up to 30% of endometrial cancers, 20% of colon
cancers, and 22% of ovarian cancers were estimated to be
attributable to overweight and obesity.37
Based on the findings of epidemiologic studies, the Inter-
national Agency for Research on Cancer (IARC) has con-
cluded that sufficient evidence exists to demonstrate that the
avoidance of weight gain over time can be an effective pre-
ventive strategy for colorectal cancer, postmenopausal breast
cancer, endometrial cancer, kidney cancer, and esophageal
cancer.38 Successful obesity prevention and management strat-
egies may prevent the substantial morbidity and early mortality
associated with common cancers.
Pulmonary Disease
Obesity increases respiratory demand and has an important
effect on pulmonary function that can predispose an indi-
vidual to a range of pulmonary problems, including obstruc-
tive sleep apnea and obesity hypoventilation syndrome. The
reduced pulmonary function common in obesity results in
dyspnea and decreased exercise capacity, which can con-
tribute substantially to poor quality of life.39
Obesity has been found to be a primary risk factor for the
development of sleep apnea. One observational study found
that subjects with obstructive sleep apnea exhibited substan-
tially greater BMI, waist circumference, percentage of body
fat, and fat mass than did controls.40 Obstructive sleep
apnea not only was associated with excess weight but also
was linked to features of the metabolic syndrome, including
increased blood pressure, increased fasting insulin levels,
increased triglyceride concentrations, decreased HDL cho-
lesterol levels, and an increased total cholesterol–to–HDL
cholesterol ratio.40 Moreover, obesity has been identified as
an important risk factor for mortality in persons with sleep
apnea.41
Musculoskeletal Disorders
Musculoskeletal problems are also common in obesity be-
cause of the added strain on bones and joints due to exces-
sive body weight. Obesity carries a greater risk of osteoar-
thritis of weight-bearing joints, especially the knees,
because of the chronic loading of the musculoskeletal sys-
tem with walking and other daily tasks.42 In a meta-analysis
of randomized controlled trials, researchers noted that dis-
ability associated with knee osteoarthritis was significantly
The American Journal of Medicine, Vol 122, No 4A, April 2009
improved with weight reductions of ⬎5.1% over a 20-week
period.43 Plantar heel pain, or plantar fasciitis, is also com-
mon in obesity because of chronic excessive weight load on
the heel. Whereas obesity may provide a protective benefit
against hip and wrist fractures in the elderly, obese children
are more vulnerable to wrist fractures. Overall, the muscu-
loskeletal problems associated with obesity carry a 4-fold
higher risk of pain that restricts work.42 Weight loss is often
the most important therapy for musculoskeletal problems
associated with obesity. Along with the observed impact of
obesity on pulmonary function, the long-term morbidity
associated with osteoarthritis, plantar fasciitis, and other
musculoskeletal conditions may be important factors that
limit exercise and hamper achievement of weight loss rec-
ommendations in obesity.
Gastrointestinal and Hepatic Disorders
Obesity predisposes individuals to gastrointestinal and he-
patic complications that contribute to morbidity and possi-
ble mortality. Nonalcoholic fatty liver disease, or hepatic
steatosis, is the most common chronic liver disease in the
United States44; it can be hypothesized that increasing rates
are linked to the obesity epidemic, because the most impor-
tant risk factors for hepatic steatosis are obesity, insulin
resistance, and hyperlipidemia.44,45 An analysis of data
from NHANES found that factors associated with elevated
alanine aminotransferase (ALT) levels, which may signal
the presence of liver dysfunction, included higher BMI,
waist-to-hip circumference ratio, and fasting serum leptin,
triglyceride, insulin, and glucose concentrations.46 Investi-
gators concluded that 65% of elevated ALT activity was
related to overweight and obesity (BMI ⱖ25). Although
hepatic steatosis does not progress to substantial complica-
tions in most patients, up to 3% of patients develop cirrhosis.
Moreover, obesity is a major risk factor for the development
of hepatic fibrosis, which can lead to cirrhosis, hepatocel-
lular carcinoma, and early mortality.44
Gallbladder disease is another common complication of
obesity, and abdominal obesity may further increase the risk
of developing this condition. In the Health Professionals
Follow-Up Study (HPFS), abdominal obesity, as measured
by waist circumference and waist-to-hip ratio, was associ-
ated with a significant increase in the risk of developing
symptomatic gallbladder disease (P ⬍0.001).47 This effect
persisted even when findings were adjusted for BMI.
Reproductive Disorders
Reproductive problems are commonly associated with obe-
sity in both women and men. In women, obesity substan-
tially increases risk for polycystic ovary syndrome (PCOS).
One study reported a 28.3% rate of PCOS in premenopausal
overweight and obese subjects, compared with a 5-fold
lower rate of 5.5% in matched lean women.48 Furthermore,
individuals with PCOS were more likely to exhibit insulin
resistance than were matched controls with similar BMI and
obesity severity.
Brown et al Obesity and Health Concerns
Table 2 Potential Health Concerns Associated with Obesity
Organ System/
Disease State Health Effects
Cancers Men: esophageal cancer, stomach cancer,
colorectal cancer, liver cancer, gallbladder
cancer, pancreatic cancer, prostate cancer,
kidney cancer, non-Hodgkin’s lymphoma,
multiple myeloma, leukemia
Women: uterine cancer, cervical cancer,
ovarian cancer, breast cancer, colorectal
cancer, liver cancer, gallbladder cancer,
kidney cancer, non-Hodgkin’s lymphoma,
multiple myeloma
Cardiovascular Atherosclerosis, myocardial infarction, stroke
Dermatologic Acanthosis nigricans, skin tags, acne, boils,
hirsutism, pathologies of augmented folds,
plantar hyperkeratosis, cellulite, stretch
marks, varicose veins
Endocrine Insulin resistance, type 2 diabetes mellitus
Gastrointestinal Nonalcoholic fatty liver disease, gallbladder
disease
Musculoskeletal Osteoarthritis and degenerative joint
disease, changes in foot anatomy due to
excess load
Pulmonary Obstructive sleep apnea
Reproductive Men: premature testosterone decline,
erectile dysfunction
Women: polycystic ovary syndrome
Obesity can also lead to substantial reproductive prob-
lems in men, including premature testosterone decline and
erectile dysfunction. Data from 2 lipid treatment trials that
collected baseline total serum testosterone levels were
pooled to examine the effects of BMI and the metabolic
syndrome on testosterone levels.49 The authors reported a
significant correlation between low testosterone levels in
aging men (mean age, 52 years) and the presence of the
metabolic syndrome (P ⬍0.0001). The components of the
metabolic syndrome linked to this effect included obesity,
diabetes, and hypertriglyceridemia. Another study found
that abdominal obesity significantly increased risk for erec-
tile dysfunction in men 61 to 81 years of age who did not
have other important comorbidities, including diabetes and
hypertension (P ⱕ0.04).50 In a study of men who had
undergone bariatric surgery to address severe obesity, re-
searchers reported significant weight loss 1 year after bari-
atric surgery (P ⬍0.001) and found that testosterone levels
were inversely proportional to BMI and fat mass.51 The
correction of severe obesity with bariatric surgery normal-
ized testosterone levels in all subjects and improved sexual
performance in 80%.
Dermatologic Disease
Many dermatologic complications are also associated with
obesity and the metabolic syndrome. Insulin resistance and
S9
obesity can result in important cellular changes that can lead
to acanthosis nigricans, a disorder characterized by dark
plaques, and skin tags. Up to 74% of obese individuals
exhibited acanthosis nigricans and skin tags in one analy-
sis.52 Importantly, acanthosis nigricans and skin tags are
markers of insulin resistance in obesity based on the fact
that hyperinsulinemia causes the cellular changes that result
in these conditions.53 The hyperandrogenism in obesity also
results in important skin manifestations, including acne,
boils, and hirsutism.53 Plantar hyperkeratosis is another
common condition in obesity characterized by chronic cal-
luses that develop in response to changes in the anatomy of
the foot due to excessive weight load.53,54 Stretch marks,
varicose veins, intertrigo (friction-related injury associated
with fat folds), and cellulite may also be produced or exac-
erbated by obesity.53
A summary of the potential health concerns associated
with excess weight is presented in Table 2. The increased
risk of developing this wide range of health problems un-
derscores the importance of obesity prevention and man-
agement in clinical practice.
SUMMARY
The obesity epidemic requires new strategies to mitigate the
substantial health effects linked to excess body weight. The
health risks associated with overweight and obesity are con-
siderable. They require an increased level of intensive pa-
tient management to address healthy weight maintenance,
and suggested strategies to achieve and maintain weight
loss. A greater public awareness of obesity and health risks
is required to move past the potential stigma associated with
discussing weight so that clinicians and patients can work
together to achieve long-term health goals.
AUTHOR DISCLOSURES
The authors who contributed to this article have disclosed
the following industry relationships:
W. Virgil Brown, MD, is a consultant for Abbott Laborato-
ries, AstraZeneca, AtherGenics, Inc, Bayer, Bristol-Myers
Squibb Company, Merck & Co, Inc, Pfizer Inc, Reliant
Pharmaceuticals, Inc, Daiichi Sankyo Co, Ltd, and Scher-
ing-Plough Corporation; is a speaker and advisory com-
mittee member for Abbott Laboratories, AstraZeneca,
Merck & Co, Inc, Pfizer Inc, and Schering-Plough Corpo-
ration; and has received grant research support from Ab-
bott Laboratories, AstraZeneca, Eli Lilly and Company,
Kos Pharmaceuticals, Inc, Merck & Co, Inc, Pfizer Inc,
Schering-Plough Corporation, and Takeda Pharmaceuti-
cals North America, Inc.
Ken Fujioka, MD, has disclosed that the commercial en-
tities with which he has relationships do not produce
healthcare-related products or services relevant to the
content he is planning, developing, or presenting for this
activity.
S10
Peter W. F. Wilson, MD, has received grant support from
GlaxoSmithKline, sanofi-aventis Pharmaceuticals, Inc,
and Wyeth.
Kristina A. Woodworth has no relevant financial relation-
ships with a commercial entity producing healthcare-
related products and/or services.
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Supplement issue

Regulation of Energy Homeostasis and Health

Consequences in Obesity
Judith Korner, MD, PhD,a Stephen C. Woods, PhD,b Kristina A. Woodworthc
a
Department of Medicine, Columbia University College of Physicians and Surgeons, and Weight Control Center, Columbia University
Medical Center, New York, New York, USA; bObesity Research Center and Department of Psychiatry, University of Cincinnati,
Cincinnati, Ohio, USA; and cSciMantis Communications, Inc, Pen Argyl, Pennsylvania, USA.

ABSTRACT

The growing awareness of the obesity epidemic as a critical matter of health concern has prompted research
into the mechanisms underlying energy homeostasis and the pathophysiology of obesity. Food intake,
energy expenditure, and fat storage all are regulated by a complex neuroendocrine system. It is now
recognized that in addition to central neurohumoral pathways, adipose tissue has an independent endocrine
function that contributes to energy homeostasis. Moreover, adipose tissue exerts inflammatory effects that
are linked to the most important health problems associated with obesity, including cardiovascular disease
and type 2 diabetes mellitus, each of which has the potential to confer long-term morbidity and increased
mortality risks. This inflammatory effect of adipose tissue is more pronounced in abdominal obesity, which
is reflected by the heightened cardiometabolic risk observed in persons with excess abdominal adiposity.
The endocrine impact of adipose tissue on energy homeostasis and inflammation highlights the critical
health implications of obesity, particularly abdominal obesity, and the importance of effective prevention
and management strategies in clinical practice.
© 2009 Elsevier Inc. All rights reserved. • The American Journal of Medicine (2009) 122, S12–S18

KEYWORDS: Endocannabinoids; Metabolic syndrome; Gut hormones; Visceral adiposity; Melanocortin system

A complex neuroendocrine system that regulates energy intake
and energy expenditure, and ultimately affects the amount of
energy stored as fat, has been uncovered.1 It is now recognized
that adipose tissue plays an independent endocrine role that
may result in an inflammatory response that increases the risk
of cardiovascular disease and type 2 diabetes mellitus,2-4 syn-
dromes that can result in substantial morbidity and early mor-
tality. This review provides an overview of the underlying
mechanisms of energy homeostasis, important regulatory sys-
tems that affect energy homeostasis and fat storage, and the
endocrine effects of visceral abdominal fat.
from the gastrointestinal system, central nervous system,
and adipose tissue, among other sources, to regulate both
short-term and long-term balances between energy intake
and energy expenditure (Figure 1).1,5-7 Meal initiation in
humans is likely to be influenced by a variety of environ-
mental factors, such as food availability and palatability,
emotions, and time of day; by contrast, meal size and meal
cessation are more likely to be regulated by a variety of
changes in body fuel stores and resulting adiposity signals,
in addition to neurohormonal signals emanating from the
gastrointestinal tract.1

MECHANISMS OF ENERGY HOMEOSTASIS The Hypothalamus and Energy Regulation

It is now recognized that energy homeostasis involves
a complex network of neuroendocrine signals originating
Statement of author disclosure: Please see the Author Disclosures
section at the end of this article.
Requests for reprints should be addressed to Judith Korner, MD, PhD,
Weight Control Center, Columbia University Medical Center, 650 West
168th Street, New York, New York 10032.
E-mail address: Jk181@columbia.edu
Neurotransmitters and hormones in the brain contribute to
the control of energy intake (eating) and energy expenditure
(metabolism). The arcuate nucleus in the hypothalamus of
the brain is the home of a regulatory process that controls
these functions.5 Agouti-related peptide/neuropeptide Y
(AgRP/NPY) neurons in the arcuate nucleus stimulate ap-
petite and reduce metabolism. Other types of neurons found
in the arcuate nucleus, known as proopiomelanocortin/

0002-9343/$ -see front matter © 2009 Elsevier Inc. All rights reserved.
doi:10.1016/j.amjmed.2009.01.003
Korner et al Obesity and Energy Homeostasis S13

Figure 1 Gut hormone regulation of energy homeostasis. AgRP ⫽ Agouti-

related peptide; ARC ⫽ arcuate nucleus; GLP-1 ⫽ glucagon-like peptide;
NPY ⫽ neuropeptide Y; OXM ⫽ oxyntomodulin; POMC ⫽ proopiomelan-
ocortin; PVN ⫽ paraventricular nucleus; PP ⫽ pancreatic peptide;
PYY3-36 ⫽ peptide YY3-36. (Adapted with permission from Nature.7)

cocaine- and amphetamine-regulated transcript (POMC/
CART) neurons, release ␣-melanocyte–stimulating hor-
mone, a neurotransmitter that inhibits food intake.1,5,6
Satiety- and hunger-inducing hormones and other signals
affect this regulatory system to control energy homeostasis.
For instance, peptide YY3-36 (PYY), a hormone secreted by
the gut in direct proportion to the caloric content of a meal,
decreases AgRP/NPY activity and reduces food intake in
both animals and humans.6 Meanwhile, many other hor-
mones also have potent neuroendocrine functions that con-
trol food intake and energy expenditure.
Insulin and Leptin
Insulin and leptin serve as peripheral adiposity signals to the
arcuate nucleus in the hypothalamus to control food intake
and metabolism. Both AgRP/NPY and POMC/CART neu-
rons in the arcuate express both insulin and leptin receptors,
and the direct administration of either hormone into the
brain reduces food intake.1 Insulin is secreted by the pan-
creas in response to meals and circulating nutrients, and
leptin is secreted by adipocytes, or fat cells, in proportion to
their fat content.1 Whereas both insulin and leptin levels
increase proportionately with body fat, leptin levels de-
crease more rapidly with food deprivation than with reduc-
tions in body fat content, which may occur to allow com-
pensatory mechanisms to be activated before energy stores
decrease substantially.1 Leptin may, in fact, have an espe-
cially important role in protecting against starvation as op-
posed to preventing weight gain.8
Decreased leptin secretion associated with decreased fat
stores results in a compensatory increase in appetite and
decrease in metabolism. However, beyond a certain level of
elevated fat stores and resulting increased leptin production,
few changes in appetite or metabolism have been observed.5
These findings are consistent with the fact that leptin levels
are substantially increased in obese individuals and suggest
that obesity is associated with a certain level of leptin
resistance.9
Cholecystokinin
Cholecystokinin (CCK) is a short-term satiety signal that
controls meal size but is unlikely to play an important role
in long-term weight regulation.10,11 Released by neuroen-
docrine cells in the intestinal wall in response to nutrient
S14
Figure 2 The role of endocannabinoids in energy homeostasis. Black wavy lines indicate sites at which cannabinoid
CB1 receptors are expressed. ARC ⫽ arcuate nucleus; CCK ⫽ cholecystokinin; GI ⫽ gastrointestinal; LHA ⫽ lateral
hypothalamic area; NPY ⫽ neuropeptide Y; NTS ⫽ nucleus tractus solitarii; PFA ⫽ perifornical area;
POMC ⫽ proopiomelanocortin; PVN ⫽ paraventricular nucleus; SNS ⫽ sympathetic nervous system. (Reprinted
with permission from Nature.1)
stimulation during a meal, CCK initiates neural signals to
the brain to cause meal termination.1 CCK also slows gas-
tric emptying and stimulates gallbladder contractions in
response to dietary fat intake to enhance nutrient absorp-
tion.6 The effect of CCK to reduce meal size appears to be
independent of the counterregulatory processes controlling
body fat content that occurs in the arcuate nucleus and
occurs in regions of the brain outside of the hypothalamus.1
Ghrelin
Ghrelin, a hormone secreted by the stomach, is a potent
appetite stimulator that induces subjective hunger and food
intake by stimulating AgRP/NPY function.5,6 Unlike leptin
and insulin, which have predominantly long-term implica-
tions in terms of food intake, metabolism, and body weight,
ghrelin and CCK both have significant short-term effects on
food intake. Circulating ghrelin concentrations increase pre-
prandially and decrease postprandially, suggesting a role for
ghrelin in meal initiation and/or termination. Ghrelin con-
centrations are decreased in obese individuals, indicating
that it is unlikely that ghrelin plays a major etiologic role in
their obesity. However, diet-induced weight loss is associ-
ated with an increase in plasma ghrelin levels, a factor that
may contribute to increased hunger and difficulty in the
maintenance of reduced body weight.12 It is important to
note that other endogenous signaling systems, including the
endocannabinoid system, also have been identified recently
as having a major role in regulating energy balance.
The American Journal of Medicine, Vol 122, No 4A, April 2009
REGULATION OF ENERGY HOMEOSTASIS: THE
ROLE OF THE ENDOCANNABINOID SYSTEM
As previously discussed, leptin functions as a strong medi-
ator of energy homeostasis by downregulating the neurons
that control food intake, including PYY. For example, leptin
inhibits the action of arcuate AgRP/NPY neurons, and it
also inhibits endocannabinoid activity in the hypothala-
mus.13 Like insulin and leptin levels, endocannabinoid lev-
els have been found to be increased in obesity, and it has
been suggested that endocannabinoids regulate food intake
and energy expenditure.13
Endocannabinoids play a prominent role in obesity, and
these hormones are active in numerous tissues, including the
brain, the liver, muscle, the gastrointestinal tract, and adi-
pose tissue (Figure 2).1,13 In the presence of palatable food
or other pleasant situations, endocannabinoids are released
in the brain and act on the endocannabinoid receptor can-
nabinoid-1 (CB1), which is located on presynaptic neuronal
membranes to attenuate satiety signals. This results in
continued eating despite opposing hormonal signals that
a sufficient amount of food has been consumed, i.e.,
endocannabinoids in some brain areas result in larger-
than-normal meals being consumed.
The CB1 receptor has been identified as an important
factor in obesity and cardiometabolic risk. Ravinet Trillou
and colleagues14 reported that genetically engineered
knockout mice that lacked the CB1 receptor gene were lean
Korner et al Obesity and Energy Homeostasis S15

Table 1 Cardiometabolic effects of key adipokines

Levels in
Adipokine Intra-Abdominal Obesity Hormonal Effects Cardiometabolic Impact
Adiponectin Levels 2 ● Inhibits foam cell formation and vascular remodeling (important ● Antiatherogenic
steps in the formation of atherosclerotic plaque) ● Antidiabetic
● Improves insulin sensitivity, opposes the development of
hyperglycemia
IL-6 Levels 1 ● Systemic inflammatory hormone ● Proatherogenic
● Exerts adverse, proatherogenic effects in the vasculature ● Prodiabetic
● Exacerbates insulin resistance
TNF-␣ Levels 1 ● Reduces insulin sensitivity ● Proatherogenic
● Increases free fatty acid production, resulting in ● Prodiabetic
hypertriglyceridemia
PAI-1 Levels 1 ● Increases risk for thromboembolic events ● Prothrombotic
IL ⫽ interleukin; PAI ⫽ plasminogen activator inhibitor; TNF ⫽ tumor necrosis factor; 1 ⫽ increase; 2 ⫽ decrease.

and resistant to obesity caused by excess food consumption;
the researchers concluded that CB1 likely regulates both
food intake and body weight. Another study of these CB1
knockout mice reported similar findings of decreased body
weight, reduced fat mass, and reduced food intake.15 A
critical role of endocannabinoids in energy homeostasis can
be inferred from these reports because of the observed lack
of compensation from other hormones that induce feeding
and reduce energy metabolism.
Other animal studies, some that measured endocannabi-
noid levels after different feeding patterns and others that
assessed the effect of endocannabinoid injections directly
into the hypothalamus, support an important role of the CB1
receptor and endocannabinoids in appetite and body weight
regulation.16,17 Interestingly, endocannabinoids secreted by
the upper gastrointestinal tract have also been implicated in
increasing ghrelin secretion, because ghrelin secretion was
attenuated following administration of an investigational
CB1 receptor antagonist in an animal model.18
The CB1 receptor has also been investigated as a target of
pharmacologic intervention in human obesity. In the ran-
domized, double-blind, placebo-controlled Rimonabant in
Obesity (RIO)–North America and RIO-Europe trials, re-
searchers found that the selective CB1 receptor antagonist
rimonabant effectively reduced body weight and waist cir-
cumference in obese individuals.19,20 Cardiometabolic risk
factors were also improved with rimonabant administration.
Similarly, in a randomized placebo-controlled trial of over-
weight individuals with untreated dyslipidemia, rimonabant
20 mg/day reduced weight and waist circumference, and
improved cardiometabolic risk factors to a significantly
greater degree than placebo.21 However, although rimon-
abant has resulted in promising rates of weight loss in
clinical studies, the frequency of psychiatric adverse events
has limited its potential as a marketable weight loss agent.
THE ENDOCRINE FUNCTION OF ADIPOSE TISSUE
Adipose tissue, once considered an inert storage depot for
fat, is now recognized as an endocrine organ that affects
energy homeostasis and cardiovascular health through
release of adipokines that regulate food intake, energy
expenditure, insulin sensitivity, and inflammation. The
key properties of adipokines related to the risk of cardio-
vascular disease and diabetes, or cardiometabolic risk
clustering, are listed in Table 1.2-4,22 The inflammatory
properties of some adipokines result in an increased po-
tential for atherogenesis, thrombosis, and diabetes. Inter-
leukin-6 (IL-6), for instance, stimulates hepatic produc-
tion of C-reactive protein (CRP), which is known to
increase atherogenic risk.3 CRP may add predictive value
to total cholesterol and high-density lipoprotein (HDL)
cholesterol in evaluating the risk for myocardial infarc-
tion in otherwise healthy men.23 There also is increasing
evidence that insulin resistance in liver, muscle, and
adipose tissue is associated with, and may be the result
of, increased proinflammatory cytokines.22
In contrast, the adipocyte hormone adiponectin exerts
beneficial anti-inflammatory and anti-diabetic properties.
Adiponectin enhances insulin sensitivity and inhibits a num-
ber of steps in the inflammatory process. The expression and
release of adiponectin is decreased in obese individuals3,22;
this is thought to be owing to increased CB1 receptor ac-
tivity.24 Thus, the accumulation of excess fat may, in part,
increase the risk for cardiovascular disease and diabetes
through a relative overabundance of proinflammatory cyto-
kines and a deficiency in adiponectin.
ABDOMINAL OBESITY AND CARDIOMETABOLIC
RISK
Anatomic fat location is highly determinant of the metabolic
and endocrine effects of the adipocytes associated with this
tissue. As discussed previously, adipocytes have important
proinflammatory endocrine effects that increase cardiometa-
bolic risk,22 and these risks may be particularly increased in
individuals with abdominal obesity. In a detailed analysis of
obese men, visceral adipose tissue was predictive of fasting
insulin levels and insulin– glucose response to oral glucose
load independent of the extent of obesity, the amount of
S16
subcutaneous adipose tissue, and the proportion of abdom-
inal fat as measured by the ratio of abdominal to femoral fat
deposition.25 An analysis of men of Asian Indian ethnicity
found that these individuals had a high level of body fat
relative to body mass index (BMI) and muscle mass, as well
as a high proportion of visceral abdominal fat; fasting serum
triglyceride and HDL cholesterol levels were directly cor-
related with insulin resistance and visceral fat but not sub-
cutaneous adipose tissue.26
It is hypothesized that a predominance of visceral fat in
abdominal obesity increases the rate of free fatty acid dep-
osition in the liver and that this mechanism may explain the
increased risks for insulin resistance and type 2 diabetes in
ethnic populations that have a greater genetic propensity to
store visceral fat as opposed to subcutaneous fat.22,26 Like-
wise, it has been proposed that the inability of the liver to
metabolize excessive free fatty acids from visceral fat in
abdominal obesity leads to intracellular fat accumulation.
This hypothesis, along with the proposed endocrine conse-
quences of abdominal obesity in terms of metabolism and
insulin sensitivity, provide a new framework for consider-
ing the links between abdominal adiposity and diabetes
risk.27
The association between abdominal adiposity and the
risk of developing type 2 diabetes is well established.
Hanley and colleagues28 reported that in a population of
⬎1,000 individuals, both BMI and waist circumference
correlated directly with fasting insulin levels and were
metabolic predictors of developing type 2 diabetes over a
mean follow-up period of 5.2 years. Data from the
Nurses’ Health Study likewise reported that BMI, waist
circumference, and waist-to-hip ratio were all indepen-
dent predictors of type 2 diabetes risk in women.29 Waist
circumference ⬎100 cm (⬎39 in) in men and women has
been linked to altered lipoprotein metabolism, as well as
impaired insulin metabolism.30
Clinical Relevance of the Metabolic Syndrome
The metabolic syndrome has been identified as a constella-
tion of risk factors that increase cardiometabolic risk. The
National Cholesterol Education Program Adult Treatment
Panel III (NCEP ATP III) identifies the metabolic syndrome
in individuals exhibiting ⱖ3 critical traits, including waist
circumference ⬎102 cm (⬎40 in) in men and ⬎88 cm (⬎35
in) in women, fasting triglycerides ⱖ150 mg/dL (1 mg/dL ⫽
0.01129 mmol/L), HDL cholesterol ⬍40 mg/dL in men and
⬍50 mg/dL in women (1 mg/dL ⫽ 0.02586 mmol/L), blood
pressure ⱖ130/ⱖ85 mm Hg or use of a blood pressure
medication, and impaired fasting glucose ⱖ110 mg/dL (1
mg/dL ⫽ 0.05551 mmol/L).31,32 A joint statement by the
American Heart Association (AHA) and the National Heart,
Lung, and Blood Institute (NHLBI) proposed a similar
definition but lowered the impaired fasting glucose thresh-
old to ⱖ100 mg/dL (Table 2).33,34 The medical community
continues to debate the importance of the metabolic syn-
drome in clinical practice. Some researchers contend that
the label of metabolic syndrome in individuals with height-
The American Journal of Medicine, Vol 122, No 4A, April 2009
Table 2 Criteria defining the metabolic syndrome*
Risk Factor Defining Level
†
Abdominal obesity (waist circumference) ‡
Men ⬎102 cm (⬎40 in)
Women ⬎88 cm (⬎35 in)
Triglycerides§ ⱖ150 mg/dL
HDL cholesterol储
Men ⬍40 mg/dL
Women ⬍50 mg/dL
Blood pressure ⱖ130/ⱖ85 mm Hg
Fasting glucose¶ ⱖ100 mg/dL
HDL ⫽ high-density lipoprotein.
*As defined by the National Cholesterol Education Program Expert
Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol
in Adults III (NCEP ATP III) and a joint statement by the American Heart
Association (AHA) and the National Heart, Lung, and Blood Institute
(NHLBI).
†
Thresholds decrease to 90 cm and 80 cm in Asian men and women,
respectively.
‡
Some male patients can develop multiple metabolic risk factors
when the waist circumference is only marginally increased (e.g., 94-102
cm [37-40 in]).
§
1 mg/dL ⫽ 0.01129 mmol/L.
储
1 mg/dL ⫽ 0.02586 mmol/L.
¶
1 mg/dL ⫽ 0.05551 mmol/L.
Adapted with permission from Circulation33 and JAMA.34
ened cardiometabolic risk does not offer any additional
prognostic information.32,35 Another analysis concluded
that the metabolic syndrome, as defined by NCEP ATP III,
is less predictive of cardiometabolic risk than are the Dia-
betes Risk Score and the Framingham Risk Score, because
both of these measures were tailored to specifically identify
cardiovascular and diabetes disease risk.36 However, others
still emphasize the importance of the metabolic syndrome as
an independent cardiovascular risk factor.37 Regardless of
the identification of the metabolic syndrome in individuals,
the constellation of risk factors that define this syndrome
has been shown to independently increase the risk for cor-
onary heart disease.38
Abdominal adiposity substantially increases the risk of
developing the metabolic syndrome, as defined by NCEP
ATP III, and may be an important independent predictor of
developing the associated cardiometabolic risk factors over
time. In an observational analysis that tracked subjects over
a period of 8 years, individuals with waist circumference
levels above the cutoff levels for abdominal obesity identi-
fied by NCEP ATP III for white, black and Hispanic indi-
viduals (ⱖ102 cm [ⱖ40 in] in men and ⱖ88 cm [ⱖ35 in] in
women) were 3 to 8 times more likely to develop the
metabolic syndrome than were those with waist circumfer-
ence levels ⬍94 cm (⬍37 in) in men and ⬍80 cm (⬍31 in)
in women.39 The metabolic syndrome was defined as ex-
hibiting ⱖ3 of the metabolic disorders identified in the
NCEP ATP III definition, including dyslipidemia, hyperten-
sion, or type 2 diabetes.39 Regardless of the clinical signif-
icance of the metabolic syndrome as an independent disease
Korner et al Obesity and Energy Homeostasis
entity, it is clear that abdominal obesity increases the risk
for developing the cardiometabolic risk factors that define
the syndrome.
SUMMARY
Energy homeostasis is regulated by a neuroendocrine sys-
tem that involves hormones secreted by the gut, central
nervous system, and other sources, including adipose tissue.
The endocrine effects of adipose tissue include a proinflam-
matory effect that contributes to the insulin resistance and
atherosclerosis associated with overweight and obesity. In
particular, evidence now suggests that excessive visceral fat
is an important source of inflammation, and persons who
exhibit abdominal obesity may be at higher risk for cardio-
metabolic disease that results in excess morbidity and mor-
tality risk. Abdominal adiposity is a critical diagnostic tool
to determine overall cardiometabolic risk in overweight and
obesity, and patients should be assessed for BMI, as well as
waist circumference, to determine global health risk profiles
in clinical practice.
Author Disclosures
The authors who contributed to this article have disclosed
the following industry relationships:
Judith Korner, MD, PhD, is a consultant for GlaxoSmith-
Kline and a paid speaker for Merck & Co, Inc, and
sanofi-aventis Pharmaceuticals, Inc.
Stephen C. Woods, PhD, is a consultant and paid speaker
for sanofi-aventis Pharmaceuticals, Inc.
Kristina A. Woodworth has no relevant financial relation-
ships with a commercial entity producing healthcare-
related products and/or services.
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Supplement issue

Obesity Prevention: Recommended Strategies

and Challenges
Anne M. Wolf, RD, MS,a Kristina A. Woodworthb
a
Department of Public Health Sciences, University of Virginia School of Medicine, Charlottesville, Virginia, USA; and bSciMantis
Communications, Inc, Pen Argyl, Pennsylvania, USA.

ABSTRACT

Lifelong healthy weight maintenance is an important goal for all Americans to avoid the health problems
associated with excessive body weight. In those who are overweight, even modest weight loss can reduce the
risk of developing diseases associated with obesity. Federal health agencies, including the Centers for Disease
Control and Prevention and the US Department of Agriculture, have recognized the critical nature of the obesity
epidemic and the importance of lifelong weight management. As a result, these agencies have published
evidence-based dietary and exercise recommendations, as well as analyses of population-based efforts to
achieve weight loss that specifically address strategies to maintain a healthy weight. Despite the availability of
recommendations and increased public education efforts, however, obesity rates continue to climb. The rising
prevalence of obesity in the United States suggests that current efforts to control weight have been inadequate.
Large-scale prevention programs that involve interventions targeting individuals as well as the larger commu-
nity, including initiatives spearheaded through workplaces and schools, are needed to control weight and reduce
the risk of long-term health consequences.
© 2009 Elsevier Inc. All rights reserved. • The American Journal of Medicine (2009) 122, S19 –S23

KEYWORDS: Prevention; Obesity; Diet; Physical activity

INTRODUCTION epidemic trend in American children by 2015.5 This review

Weight maintenance is an important lifelong health goal to
reduce the risk of cardiometabolic complications and other
substantial health problems that can arise with overweight
and obesity. Lifestyle interventions that achieve even mod-
est weight loss may reduce the risk of developing type 2
diabetes mellitus in overweight individuals with insulin
resistance.1-3 Likewise, modest reductions in abdominal fat
may reduce overall cardiometabolic risk.4 The substantial
health benefits of healthy weight management are now rec-
ognized and have resulted in a call for large-scale preven-
tion efforts. The likely benefits of obesity prevention have
been recognized by organizations devoted to public health,
including the Robert Wood Johnson Foundation. The foun-
dation has vowed to devote $500 million in funds to combat
childhood obesity, with a goal of reversing the obesity
discusses current dietary and exercise guidelines for healthy
weight maintenance, the call to action for large-scale obe-
sity prevention strategies, the role that the community can
play in helping individuals achieve long-term weight man-
agement goals, and the barriers to implementing effective
obesity prevention programs.
CENTERS FOR DISEASE CONTROL AND
PREVENTION OBESITY CONTROL EFFORTS
The Centers for Disease Control and Prevention (CDC) has
examined the importance of population-based efforts to control
obesity and increase physical activity. Results from these anal-
yses are available in the CDC Guide to Community Preventive
Services as a resource for local officials to develop community-
specific and site-specific plans to improve health.6

Statement of author disclosure: Please see the Author Disclosures
section at the end of this article.
Requests for reprints should be addressed to Anne M. Wolf, RD, MS,
Department of Public Health Sciences, University of Virginia School of
Medicine, 5030 Rutherford Rd, Charlottesville, VA 22901.
E-mail address: AMW6N@virginia.edu
Population-Based Interventions
The CDC Guide to Community Preventive Services provides a
systematic review of the effectiveness of population-based
interventions in preventing obesity, including school-based
interventions, worksite interventions, healthcare system inter-

0002-9343/$ -see front matter © 2009 Elsevier Inc. All rights reserved.
doi:10.1016/j.amjmed.2009.01.004
S20 The American Journal of Medicine, Vol 122, No 4A, April 2009

Table 1 Centers for Disease Control and Prevention (CDC) Evidence-Based Recommendations for Promoting Physical Activity

Intervention
Informational approaches
Community-wide campaigns
“Point-of-decision” prompts
Behavioral and social approaches
Individually adapted health behavior change
programs
School-based physical education
Nonfamily social support
Environmental and policy approaches
Creation of and/or enhanced access to
places for physical activity combined
with informational outreach activities
Adapted from Physical activity, 2007 in The Community Guide.8
Description
Large-scale, highly visible, community-wide campaigns through television, radio,
newspapers, movie theaters, billboards, and mailings
Signs posted at elevators and escalators encouraging individuals to use stairs
Teach behavioral skills to help incorporate physical activity into daily routines
Longer classes, encouraging students to be more active during class
Social networks of exercise groups
Groups working to change the environment to promote physical activity with the
creation of, or improved access to, for example, walking trails and exercise
facilities.

ventions, and community-wide interventions.6 Analyses have
been completed for school-based interventions and inter-
ventions in the workplace.
Worksite interventions are supported by the available
literature and were therefore recommended by the CDC to
combat obesity. The CDC suggests multicomponent inter-
ventions that target diet, physical activity, and behavioral
changes, because these strategies have been found to be
effective when delivered through the workplace.6 Single-
component programs that targeted only nutrition, physical
activity, or behavioral intervention lacked sufficient evi-
dence for support based on systematic reviews.7 The CDC
report noted that worksite interventions to prevent and con-
trol overweight and obesity are cost-effective, with an esti-
mated cost of less than $1 per employee per year to reach
1% of the population at risk, which may be an important
selling point in encouraging employers to support these
onsite programs.7 A full summary of the systematic reviews
that resulted in the CDC recommendations for obesity pre-
vention in schools and the workplace was published in
2005.7
Although insufficient evidence is available to fully rec-
ommend systematic school-based interventions, the CDC
guide noted that several program elements should be con-
sidered when designing future policies aimed at combating
childhood obesity. Modest positive changes were found
with interventions that integrated nutritional education with
physical activity; allotted additional time for physical activ-
ity during the school day; included noncompetitive sports,
such as dance, in the physical education curriculum; and
emphasized the limitations of sedentary activities, espe-
cially television viewing. Internet use and video games were
also cited as possible sources of additional sedentary time
that were worthy of future investigation.7
Physical Activity Recommendations
The CDC Guide to Community Preventive Services likewise
offers a systematic review of efforts designed to increase phys-
ical activity, including informational approaches, behavioral
and social approaches, and environmental and policy ap-
proaches.7 The CDC review of the literature has identified
multiple strategies for increasing physical activity that are
strongly supported by the literature. These strategies are
summarized in Table 1, and additional details are available
in the published document.8 Additional strategies to pro-
mote physical activity are currently under review, including
transportation policy and infrastructure changes to promote
nonmotorized transit and new urban planning approaches
that change zoning and land use.8
US DEPARTMENT OF AGRICULTURE DIETARY
GUIDELINES AND WEIGHT CONTROL
The US Department of Agriculture (USDA) Dietary Guide-
lines for Americans are updated every 5 years and were last
published in 2005.9 Individuals should be encouraged to
follow these established dietary guidelines regularly for
long-term weight maintenance.
The guidelines stress the importance of a diet rich in
fruits and vegetables, suggesting that individuals with a
2,000-calorie daily target should consume 2 cups of fruits
and 2.5 cups of vegetables each day (1 c ⫽ 0.24 L), which
translates to ⱖ9 daily servings of fruits and vegetables.
Furthermore, the guidelines emphasize that individuals
should choose a variety of fruits and vegetables from all 5
vegetable subgroups (dark green, orange, legumes, starchy
vegetables, and other vegetables) several times each week.9
In support of these recommendations, the CDC offers pub-
lications to support a large-scale campaign to increase fruit
and vegetable consumption.10
The USDA also recommends that individuals consume
ⱖ3 ounce-equivalent (1 oz ⫽ 30 mL) servings of whole
grain products daily and emphasizes that ⱖ50% of grain
products consumed should come from whole grains.9 This
level of whole grains in the diet, along with suggested
amounts of fruits and vegetables, contributes to the daily
Wolf and Woodworth Strategies and Challenges in Obesity Prevention S21

Table 2 Key Recommendations of the US Department of Agriculture (USDA) Dietary Guidelines for Americans, 2005

Category Recommendations at the 2,000-Calorie Level

Food group
Fruits and vegetables Choose a diet rich in fruits and vegetables, consuming 2 cups of fruits and
2.5 cups* of vegetables each day, which translates to ⱖ9 daily servings
Grains Consume ⱖ3 or more ounce-equivalent† servings of whole-grain products
daily; ⱖ50% of grain products consumed should come from whole grains
Macronutrients
Fiber 28 g/day
Total fat 20%-35% of calories consumed should come from fat
Saturated fat ⬍10% of calories consumed should come from saturated fat
Physical activity
To prevent chronic disease ⱖ30 min of moderate-intensity physical activity on most days of the week
To help manage body weight and avoid weight gain ⱖ60 min of moderate- to vigorous-intensity physical activity on most days
of the week
To help maintain weight loss 60-90 min of moderate-intensity physical activity daily
Adapted from Dietary Guidelines for Americans.9
*1 c ⫽ 0.24 L.
†
1 oz ⫽ 30 mL.

fiber intake of 25 to 30 g/day recommended by the USDA A TOXIC ENVIRONMENT: INCREASED

and the American Heart Association (AHA).11 Of note,
Howarth and colleagues12 found that high-fiber diets of 25
to 30 g/day increase satiety, reduce hunger, and improve
weight loss. The authors concluded that the prevalence of
obesity could be reduced if individuals increased target
daily fiber levels from 15 g to 25 to 30 g, with the goal
achieved by replacing refined grain products with whole
grains and increasing fruit and vegetable consumption.
According to the USDA guidelines, individuals should
limit total fat intake to 20% to 35% of daily calories, with
most fats coming from polyunsaturated or monounsaturated
sources.9 Meta-analyses of low-fat diets that consist of only
25% to 30% of total calories from fat confirm that these
recommendations likely contribute to weight loss. One
meta-analysis of 16 studies of low-fat diets with 19 inter-
vention groups concluded that this dietary strategy results in
weight loss of 3.2 kg greater than that in control groups.13
Another meta-analysis of 37 studies likewise found a pos-
itive correlation between fat intake and weight loss.14
The 2005 update of the USDA dietary guidelines repre-
sents the first time that physical activity recommendations
were offered, with the goals of promoting health, psycho-
logical well-being, and weight maintenance.9 The guide-
lines recommend that adults should engage in ⱖ30 minutes
of moderate-intensity physical activity on most days of the
week to prevent chronic disease. To help manage body
weight and avoid weight gain, the guidelines suggest that
individuals should engage in ⱖ60 minutes of moderate-
to vigorous-intensity activity on most days of the week;
to help maintain weight loss, moderate-intensity exercise
of 60 to 90 minutes daily is recommended. A summary of
the USDA dietary and exercise guidelines is presented in
Table 2.9
AVAILABILITY AND CONSUMPTION OF
UNHEALTHY FOODS
Portion Control, Sugar-Sweetened Drinks,
and Sodium Intake
Portion control at each meal is critical to maintain weight
and prevent weight gain over time, and has been cited as an
important contributor to the current obesity epidemic. Rolls
and associates15 demonstrated a significant relation between
the amount of a particular food (macaroni and cheese)
offered at each meal and the amount of that food consumed
(P ⬍0.0001). The authors noted that in contrast to obser-
vations from previous studies, larger portion sizes led to
greater amounts of energy consumed: overall, 30% more
energy was consumed with the largest portion size com-
pared with energy consumed with the smallest portion size.
These findings stress the importance of portion control and
highlight the likely health ramifications of convenience
foods that are offered in ever-increasing portion sizes.
The habitual consumption of high-calorie, sugar-based
drinks is another appropriate target to control daily energy
intake and prevent weight gain. In another study by Rolls
and associates,16 sugar-based drinks consumed with meals
increased the overall energy intake during the meal because
individuals demonstrated a lack of compensation by con-
suming fewer food calories during the meal. Drinks sweet-
ened with the artificial sweetener aspartame, meanwhile, did
not increase the amount of food consumed during the meal
and therefore did not increase energy intake. Sugar-based
drinks also had a lower ability to quench thirst than did
aspartame-sweetened drinks and water, suggesting that a
higher amount of sugar-based drink, and consequently a
greater energy intake, may be consumed during a meal if
this type of drink is chosen as a meal accompaniment.16 In
S22
school-aged children, the incidence of childhood obesity
was found to be 1.6 times greater with each serving of
sugar-sweetened drinks consumed per day. Likewise, base-
line consumption of sugar-based drinks and changes in
consumption over the course of the study independently
predicted changes in body mass index (BMI).17 Interven-
tions that stress reductions in the amount of sugar-based
drinks consumed may have an important impact on obesity
prevention.
Increases in sodium intake by the American population
in recent decades may be another important underlying
factor in the current obesity epidemic. According to the Salt
Institute, a North American trade organization, total pur-
chases of salt intended for human consumption in the
United States increased by 86%, and per capita sales in-
creased by 55%, between 1983 and 1998.18 Meanwhile,
energy consumption from sugar-sweetened beverages in-
creased by 135% from 1977 to 2001, and milk consumption
declined by 38% during the same period. A higher level of
dietary sodium results in a greater degree of thirst, which
may contribute to obesity in an environment of high levels
of energy consumed from sugar-sweetened drinks, espe-
cially carbonated soft drinks. Overall, it is estimated that
Americans now consume an additional 278 calories each
day because of changes in patterns of drink consumption.18
Food Consumption Outside of the Home
An increase in the number of meals consumed outside of the
home and a simultaneous decrease in the number of meals
prepared at home have also been cited as contributing to the
problem of obesity. In a study of 73 adults who completed
questionnaires on the frequency of food intake from various
restaurant settings, McCrory and coworkers19 reported that
the frequency of eating foods from restaurants serving fried
chicken, burgers, pizza, Chinese food, Mexican food, fried
fish, and other convenience foods was directly associated
with body fatness. A greater frequency of consuming these
restaurant foods was also associated with higher levels of
total fat and saturated fat intake and lower levels of fiber
intake. Although healthy meals prepared at home may be
ideal, public education efforts should at least emphasize
healthy food choices and closer attention to restaurant and
convenience foods consumed on a regular basis.
Current patterns of food consumption in the United
States highlight the importance of public education efforts
designed to improve eating habits and public health.
Whereas education may be 1 component in a larger strategy
to reduce the obesity trend, society-wide changes will ulti-
mately be necessary to bring about lasting change.
THE ROLE OF THE COMMUNITY IN OBESITY
PREVENTION
Society can play a critical role in supporting obesity pre-
vention efforts. As suggested by the CDC recommendations
for physical activity,8 obesity prevention strategies should
recognize the limitations of individual lifestyle changes
The American Journal of Medicine, Vol 122, No 4A, April 2009
when the surrounding environment and community do not
support these efforts.
Prevention efforts should be designed to exert influence at
the level of the individual, the overall community environment,
and governmental policy. Social networks, including churches,
community groups, schools, and other organizations, are im-
portant targets for intervention to achieve large-scale obesity
prevention at the population level.20
Obesity Prevention: A Global Call to Action
The obesity crisis has been highlighted by the fact that the
World Health Organization (WHO) has recognized obesity
as a critical concern that needs to be addressed through
global health policy. The Global Alliance for the Prevention
of Obesity and Related Chronic Disease is a worldwide
initiative to combat obesity and comprises 5 organizations
linked to the WHO, including the International Association
for the Study of Obesity (IASO), the World Heart Federa-
tion (WHF), the International Diabetes Federation (IDF),
the International Pediatric Association (IPA), and the Inter-
national Union of Nutritional Sciences (IUNS). In response
to a call to action from the WHO to prevent chronic disease
linked to unhealthy diet, sedentary lifestyles, and tobacco
use, the Alliance is now in the process of developing guide-
lines that focus on preventing childhood obesity through
improvements in diet and physical activity, as well as de-
veloping local, best-practice prevention models.21
CHALLENGES IN ACHIEVING WEIGHT LOSS AND
MAINTAINING WEIGHT
Despite increasing levels of concern and the introduction of
large-scale public health initiatives, obesity prevention ef-
forts to date have been essentially ineffective in reversing
obesity trends in the United States. The Trust for America’s
Health, a nonpartisan health advocacy organization, has
reported that US obesity prevention efforts are failing.22
The organization cites several critical barriers to effective
obesity prevention: funds and political prioritization are
lacking to support sustained obesity prevention efforts; obe-
sity research is not being translated effectively into clinical
practice; the public perceives obesity as an individual con-
cern; and current measurements of success and behavior
change, including BMI and weight loss, are limited. Public
education programs that highlight the health risks of over-
weight and obesity may be required to motivate individuals
to lose weight. Moreover, substantial policy changes are
necessary to promote obesity prevention efforts.
SUMMARY
The high prevalence of obesity represents a public health
crisis that requires effective prevention efforts to stem the
rising costs of managing cardiometabolic risk and other
substantial health problems that arise with excessive body
weight. Although the problem of obesity is now being
recognized with large-scale prevention efforts, it is clear
that treatment strategies are needed to address the health
Wolf and Woodworth Strategies and Challenges in Obesity Prevention
risks and resulting medical costs in the large population of
individuals who already suffer from obesity. Lifestyle mod-
ification that emphasizes a healthy diet and regular exercise
is the ideal route to combat overweight and obesity, but
many individuals may realize lasting weight loss only with
advanced treatment interventions. Current obesity prevention
efforts should be driven by interventions through schools and
worksites that promote healthy diets and regular exercise, and
these interventions should be complemented by larger envi-
ronmental and policy initiatives that expand opportunities
for physical activity.
AUTHOR DISCLOSURES
The authors who contributed to this article have disclosed
the following industry relationships:
Anne M. Wolf, RD, MS, has disclosed that the commercial
entities with which she has relationships do not produce
healthcare-related products or services relevant to the
content she is planning, developing, or presenting for
this activity.
Kristina A. Woodworth has no relevant financial relation-
ships with a commercial entity producing healthcare-
related products and/or services.
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4. Després JP. Dyslipidaemia and obesity. Baillières Clin Endocrinol
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ment to Reverse Childhood Obesity in US [press release]. Princeton,
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http://www.rwjf.org/newsroom/product.jsp?id⫽21938. Accessed De-
cember 14, 2008.
6. Centers for Disease Control and Prevention (CDC). Guide to Commu-
nity Preventive Services (The Community Guide). [CDC Website.]
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org/obese/default.htm. Accessed March 24, 2008.
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[CDC Website.] Updated December 7, 2004. Available at: http://
www.thecommunityguide.org/pa/. Accessed March 24, 2008.
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Agriculture (USDA). Dietary Guidelines for Americans. [HHS Website.]
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11. Krauss RM, Deckelbaum RJ, Ernst N, et al. Dietary guidelines for
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12. Howarth NC, Saltzman E, Roberts SB. Dietary fiber and weight
regulation. Nutr Rev. 2001;59:129-139.
13. Astrup A, Grunwald GK, Melanson EL, Saris WH, Hill JO. The role
of low-fat diets in body weight control: a meta-analysis of ad libitum
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1545-1552.
14. Yu-Poth S, Zhao G, Etherton T, Naglak M, Jonnalagadda S, Kris-
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16. Rolls BJ, Kim S, Fedoroff IC. Effects of drinks sweetened with
sucrose or aspartame on hunger, thirst and food intake in men. Physiol
Behav. 1990;48:19-26.
17. Ludwig DS, Peterson KE, Gortmaker SL. Relation between consump-
tion of sugar-sweetened drinks and childhood obesity: a prospective,
observational analysis. Lancet. 2001;357:505-508.
18. Karppanen H, Mervaala E. Sodium intake and hypertension. Prog
Cardiovasc Dis. 2006;49:59-75.
19. McCrory MA, Fuss PJ, Hays NP, Vinken AG, Greenberg AS, Roberts
SB. Overeating in America: association between restaurant food con-
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80. Obes Res. 1999;7:564-571.
20. Stokols D. Translating social ecological theory into guidelines for
community health promotion. Am J Health Promot. 1996;10:282-298.
21. Global Alliance for the Prevention of Obesity and Related Chronic
Disease [Website]. Available at: http://www.preventionalliance.net/.
Accessed March 24, 2008.
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Failing in America, 2006 [report]. [TFAH Website.] August 2006.
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cessed March 24, 2008.
Supplement issue

When Prevention Fails: Obesity Treatment Strategies

Louis J. Aronne, MD,a Thomas Wadden, PhD,b Kathy Keenan Isoldi, MS, RD, CDE,c Kristina A. Woodworthd
a
Department of Medicine, Weill Cornell Medical College, and Comprehensive Weight Control Program, New York-Presbyterian
Hospital, New York, New York, USA; bDepartment of Psychology, University of Pennsylvania School of Medicine, and Center for
Weight and Eating Disorders, University of Pennsylvania, Philadelphia, Pennsylvania, USA; cClinical Nutrition Services,
Comprehensive Weight Control Program, New York-Presbyterian Hospital, New York, New York, USA; and dSciMantis
Communications, Inc, Pen Argyl, Pennsylvania, USA

ABSTRACT

The obesity epidemic has resulted in increasingly urgent calls for large-scale prevention strategies.
Meanwhile, effective treatment approaches that result in sustainable weight loss are needed to attenuate the
cardiometabolic risks that may lead to comorbid illnesses and early mortality. Public education efforts
geared toward those afflicted with obesity should emphasize that a relatively modest reduction in body
weight dramatically reduces disease risk, thereby improving overall long-term health. Setting realistic
weight loss goals with patients should reduce the overwhelming frustration often associated with the belief
that large amounts of weight loss are needed for improved health. This misconception often impedes
overweight and obese individuals from seeking treatment. Effective strategies are available to help overweight
and obese individuals achieve reasonable weight loss goals. Important challenges exist in preventing
weight regain following weight loss intervention. Studies are underway to identify new therapeutic
strategies to effectively reduce weight, as well as to provide long-term data on successful weight loss
maintenance strategies.
© 2009 Published by Elsevier Inc. • The American Journal of Medicine (2009) 122, S24 –S32

KEYWORDS: Exercise; Diet and lifestyle intervention; Obesity treatment; Pharmacotherapy; Weight loss

Obesity rates in the United States have more than doubled
from 1960 to 2000,1 suggesting that current efforts to pre-
vent excess weight gain in this country have been unsuc-
cessful. Obesity confers an increased risk of developing
debilitating and life-threatening illnesses, including cardio-
vascular disease and type 2 diabetes mellitus, that often
leads to substantial comorbid disease burden and early mor-
tality.2 Substantial health benefits can be realized with rel-
atively modest weight loss.3,4 However, research reports
indicate that many obese individuals unrealistically desire to
lose ⬎25% of their body weight.5 Public education efforts
should stress the benefits of modest, obtainable weight loss
to encourage overweight and obese individuals to engage in
weight loss interventions. Effective strategies, including
lifestyle interventions that emphasize calorie restrictions
Statement of author disclosure: Please see the Author Disclosures
section at the end of this article.
Requests for reprints should be addressed to Louis J. Aronne, MD,
Weill Cornell Medical College, Comprehensive Weight Control Program,
New York-Presbyterian Hospital, 1165 York Avenue, New York, New
York 10028.
E-mail address: ljaronne@med.cornell.edu
and increased physical activity, as well as appropriate phar-
macologic treatments, have been shown to promote modest
weight loss.6,7 However, many individuals continue to en-
counter multiple obstacles that prevent maintenance of lost
weight over long periods.
Strategies that reduce weight and maintain weight loss
over time should be made available to all overweight and
obese individuals; however, individuals who are most vul-
nerable to substantial, long-term health risks should be
targeted for intensive risk factor reduction. Treatment strat-
egies, including novel pharmacologic options, are being
investigated for their role in reducing weight and supporting
long-term weight loss in obese individuals. This review
highlights important issues in obesity treatment and the role
of multifaceted management strategies in achieving long-
term weight loss success.
INITIAL PATIENT PRESENTATION AND
EVALUATION
Obese and overweight patients who are at risk for health
complications should receive a complete physical examination

0002-9343/$ -see front matter © 2009 Published by Elsevier Inc.

doi:10.1016/j.amjmed.2009.01.005
Aronne et al Obesity Treatment Strategies S25

Table 1 Overweight and obesity classifications by body mass Table 2 Waist circumference thresholds for abdominal
index (BMI) obesity by race/ethnicity

Classification BMI Race/Ethnicity Men Women

Underweight ⬍18.5 White/black/Hispanic* ⬎102 cm (⬎40 in) ⬎88 cm (⬎35 in)
Normal weight 18.5-24.9 White† ⱖ94 cm (ⱖ37 in) ⱖ80 cm (ⱖ31 in)
Overweight 25-29.9 South Asian ⱖ90 cm (ⱖ35 in) ⱖ80 cm (ⱖ31 in)
Obesity (class 1) 30-34.9 Chinese ⱖ90 cm (ⱖ35 in) ⱖ80 cm (ⱖ31 in)
Obesity (class 2) 35-39.9 Japanese ⱖ85 cm (ⱖ33 in) ⱖ90 cm (ⱖ35 in)
Extreme obesity (class 3) ⱖ40 *National Cholesterol Education Program Adult Treatment Panel III
Adapted from JAMA.2 (NCEP ATP III) definition.
†
International Diabetes Federation (IDF) definition.
Adapted from Circulation,13 IDF,14 and JAMA.15

and review of blood chemistries to investigate whether excess

weight gain is owing to a physiologic cause, such as thyroid
dysfunction. Clinicians should review current medication use
with their patients to screen for likely weight gain culprits,
because many medications can induce weight gain.8,9 Medi-
cations that may promote weight gain include, but are not
limited to, common diabetes treatments (sulfonylureas, thiazol-
idinediones, insulin), antiepileptics (gabapentin, sodium val-
proate), antipsychotics (clozapine, risperidone, olanzapine),
steroid hormones (corticosteroids), tricyclic antidepressants,
and certain other antidepressants.8,10
Initial patient evaluations should include assessments of
body mass index (BMI), waist circumference, and overall
medical risk.2 The clinician should aim to evaluate the
patient’s personal motivations for wishing to lose weight. It
is important to also discuss the patient’s understanding of
the possible risks of weight loss interventions, the benefits
of effective weight loss, the patient’s history of methods and
outcomes of previous weight loss attempts, anticipated sup-
port from family and friends, personal attitudes toward
physical activity, time availability, and possible barriers to
weight loss, including financial limitations.2 Although the
content of this important discussion appears lengthy, the infor-
mation can be obtained rather quickly, will set the foundation
for continued follow-up care, and ultimately will lead to
improvement in overall weight loss outcome.
Body Mass Index
BMI is an important screening tool to assess patients with
excess body weight and stratify treatments according to the
likelihood of underlying disease risk. BMI is calculated by
dividing an individual’s weight in kilograms by the squared
product of the individual’s height in meters.2 The determi-
nation of BMI may provide a better determination of global
disease risk than does assessing the patient’s weight alone.
However, BMI is a limited diagnostic tool in very muscular
individuals and those with little muscle mass, such as el-
derly patients.2 Clinical judgment, as well as the use of
varied tools to assess risk, should aid in appropriately diag-
nosing overweight or obesity. Overweight and obesity clas-
sifications by BMI are presented in Table 1. Persons with a
BMI of 25 to 29.9 are classified as overweight, whereas
those with a BMI ⱖ30 are considered obese.2
Assessment of Abdominal Obesity
Whereas BMI is an important screening tool, waist circum-
ference provides important additional prognostic informa-
tion, especially when BMI is not substantially increased but
an unhealthy level of excessive adiposity is still suspected.11
Waist circumference correlates with abdominal obesity, the
presence of which confers a higher absolute disease risk.11
To accurately measure waist circumference, the clinician
should stand to the right of the patient and locate the
patient’s right iliac crest by palpating the upper hipbone. A
horizontal mark should be drawn at the uppermost lateral
border of the right iliac crest, and the mark should be
crossed with a vertical mark. A tape measure should be used
to measure the waist circumference at this point, taking care
to keep the plane of the tape parallel to the floor and avoid
compression of the skin with the tape. The measurement is
made at the end of a normal expiration.11
Waist circumference is an important surrogate measure
of abdominal obesity and disease risk. A higher risk for
diabetes, dyslipidemia, hypertension, and cardiovascular
disease has been associated with a waist circumference
⬎102 cm (⬎40 in) in men and ⬎88 cm (⬎35 in) in women.
One study demonstrated effective utility of waist circum-
ference as a predictor of the metabolic syndrome, type 2
diabetes, and other cardiometabolic risk factors.12 However,
waist measurements do not add any value in estimating
disease risk in individuals with a BMI ⱖ35.2 Moreover, it
should be emphasized that waist circumference thresholds for
abdominal obesity vary with race/ethnicity (Table 2).13-15 In
summary, waist circumference, along with BMI, should be
used to assess obesity, cardiovascular disease risk, and the
efficacy of weight loss regimens.11
Cardiometabolic Risk Assessment
Excess weight increases the risk of developing cardiovas-
cular and metabolic diseases and ensuing complications.
Overweight and obese individuals who have a history of
established coronary heart disease (CHD), other atheroscle-
rotic diseases, type 2 diabetes, or sleep apnea are at the
highest level of absolute risk for morbidity and mortality.2
Overweight and obese patients should be evaluated for these
conditions and managed appropriately. A high level of ab-
S26 The American Journal of Medicine, Vol 122, No 4A, April 2009

1 Patient encounter

2 Hx of ≥ 25 BMI?

Yes

3 BMI measured in past

2 years?

• Measure weight, height, BMI ≥25 OR waist 6 7 BMI ≥ 30 OR {[BMI

Yes
4 circumference > 35 in 25 to 29.9 OR waist Yes
and waist circumference
(88 cm) (F) > 40 in circumference > 35 in
8
• Calculate BMI (102 cm) (M) Assess risk factors (F) > 40 in (M)] AND ≥
2 risk factors }
Clinician and patient
devise goals and
No
14 treatment strategy for
Yes No weight loss and risk
Hx ≥ 25 BMI? 12 factor control
Yes
15 13
Does patient want to
No
lose weight?
Brief reinforcement/ Advise to maintain
9
educate on weight weight/address other
management risk factors No Progress
being made/goal
achieved?
Yes No
Periodic weight, BMI,
16 and waist
circumference check Maintenance
Assess reasons
counseling:
• Dietary therapy for failure to
lose weight
• Behavior therapy
Examination • Physical activity
10
Treatment 11

* This algorithm applies only to the assessment for overweight and obesity and subsequent decisions based on that
assessment. It does not reflect any initial overall assessment for other cardiovascular risk factors that are indicated.

Figure 1 Treatment algorithm for the assessment of patients with overweight and obesity. BMI ⫽ body mass
index; F ⫽ females; Hx ⫽ history; M ⫽ males. (Adapted with permission from The Practical Guide:
Identification, Evaluation, and Treatment of Overweight and Obesity in Adults.2)

solute risk is also associated with individuals who exhibit
ⱖ3 of the following characteristics: hypertension, cigarette
smoking, high low-density lipoprotein (LDL) cholesterol
levels, low high-density lipoprotein (HDL) cholesterol lev-
els, impaired fasting glucose, a family history of early
cardiovascular disease, and advanced age (ⱖ45 years in
men, ⱖ55 years in women).2 A suggested treatment algo-
rithm to address excess weight and cardiometabolic risk has
been developed and published by the National Heart, Lung,
and Blood Institute (NHLBI) (Figure 1).2
DECIDING ON TREATMENT
The NHLBI Practical Guide has recommended appropri-
ate weight loss therapy in patients with a BMI ⱖ30;
likewise, weight loss interventions are recommended in
patients with a BMI ⱖ25 or a high waist circumference
plus ⱖ2 risk factors.2
Clinicians should discuss available treatment options
with the patient to develop an effective weight loss strategy
that is appropriate for the level of risk and the individual’s
lifestyle. Regardless of the amount of weight a patient
wishes to lose, it is important that the patient be assured that
significant health benefit can be achieved with even modest
weight loss.
Lifestyle Intervention Using Behavioral
Modification
Lifestyle modification is recommended as the primary treat-
ment intervention for overweight and obese individuals.
Behavior modification uses strategies focusing on behavior
change targeted at reducing overeating and sedentary activ-
ities to achieve and maintain weight loss. This type of
intervention has been found to be effective in multiple,
short-term clinical trials.16
Dietary Strategies for Weight Loss. Components of the
ideal weight loss plan have been elusive, and the benefits of
the low-fat versus low-carbohydrate diet for weight loss debate
continues. Low-fat and low-carbohydrate diets have been in-
vestigated for their ability to achieve and maintain weight loss.
In a meta-analysis by Nordmann et al, 5 trials that included 447
individuals were evaluated to compare the efficacy of low-
fat interventions compared with low-carbohydrate interven-
tions in reducing weight and cardiometabolic risk factors.17
Whereas those following the low-carbohydrate diets
achieved greater weight loss within the first 6 months of the
intervention, at the 12-month mark after diet initiation no
significant difference in weight loss was shown between the
2 diet types. Weight loss may have been linked to adherence
rates; investigators noted a higher rate of adherence to the
Aronne et al Obesity Treatment Strategies
low-carbohydrate diet over the first 6 months of the inter-
vention, but no detectable difference in adherence rates for
the 2 dietary strategies was found at 12 months.17
Researchers reported differences in lipid profile response
to the low-fat and low-carbohydrate diets. Greater decreases
in total cholesterol and LDL cholesterol levels were found
in patients following the low-fat diet, and increased levels of
HDL cholesterol and reduced triglyceride levels were re-
ported in patients following the low-carbohydrate diet.17
Personal preference, readiness to begin a diet program,
and the individual’s ability to incorporate a particular diet
into his or her daily routine are important determinants of
diet efficacy. Furthermore, individual physiologic response
to a particular dietary intervention appears to play an im-
portant role. In a recent trial of 73 obese adults aged 18 to
35 years, researchers found that patients with serum insulin
levels above the median following a 75-g glucose challenge
lost significantly greater amounts of weight and body fat if
they were on the low-glycemic-load diet compared with
participants who were on the low-fat diet. Researchers pos-
tulate that the difference found may be owing to variance in
individual hormonal response.18
Very-low-calorie diets (VLCDs) have waned in popularity
since the 1980s. A meta-analysis of low-calorie diets (LCDs)
and VLCDs, totaling approximately 800 cal/day, was per-
formed to determine the efficacy and safety of VLCDs.19
VLCDs consist of mainly liquid meal replacements along
with some conventional foods. Results of the meta-analysis
revealed that short-term weight loss was greater in patients
treated with VLCDs; however, long-term weight loss results
in patients treated with LCDs or VLCDs were comparable.
The authors proposed that VLCDs may have the greatest
utility if followed by a long-term management plan provid-
ing additional therapeutic support, such as pharmacologic
therapy, to sustain the initial weight loss of 15% to 25%
observed with VLCDs in other studies.19-21
Meal replacements have become popular options for
individuals who do not have time to prepare food or who
have difficulty controlling portion size. The variety of pre-
packaged meals, shakes, and snack bars has expanded over
the past few years, and the usefulness of these products in
aiding weight management has been studied. One study
compared 2 diets of identical energy intake, including a
standard diet and a diet containing meal replacements eaten
twice per day (once as a meal and once as a snack).22
Researchers found that patients receiving the meal replace-
ment diet lost a significantly greater amount of weight
(6.9% vs. 5.9% of initial weight; P ⬍0.0001) than did
patients restricted to the standard diet. Blood pressure, se-
rum triglyceride, and blood glucose levels decreased with
weight loss in both groups during the course of this
27-month study. Investigators concluded that the use of
meal replacements in conjunction with a low-fat, calorie-
restricted diet is an effective strategy for promoting weight
loss and lasting change in eating patterns.22 Support for this
premise was found in a trial of longer duration. Researchers
followed a group of dieters using 1 meal replacement, in-
S27
corporated into the daily diet in conjunction with a calorie-
restricted, low-fat diet.23 Sustained reductions in energy
intake, maintenance of weight loss, and improvements in
cardiometabolic risk factors over a span of 4 years were
reported.
Exercise and Weight Loss. Exercise is a component of any
lifestyle modification program aimed at improving health
and reducing body fat. Increasing daily physical activity
helps overweight and obese individuals achieve and main-
tain a healthy body weight. The 2005 Healthy Guidelines
for Americans, developed by the United States Department
of Agriculture (USDA) and the Department of Health and
Human Services (DHHS), recommends 60 to 90 minutes of
daily physical activity to maintain weight loss.24
Obese individuals who engage in regular exercise, re-
gardless of weight loss outcome, find improved health that
appears to attenuate cardiovascular risk. Research supports
that there are many health benefits gained in both men and
women by being physically fit. In an observational cohort
study of 21,925 men 30 to 83 years of age, Lee and col-
leagues25 reported that moderate-to-high levels of physical
fitness reduced mortality risk, regardless of body composi-
tion. Lean men in the study exhibited increased longevity
only if they also exhibited cardiorespiratory fitness. Unfit,
lean men had a 2-fold greater mortality risk than did fit, lean
men, and unfit, lean men had a greater mortality risk than
did fit, obese men. Obese men who were fit did not have an
increased mortality risk. In an analysis of 2,506 women and
2,860 men enrolled in the Lipids Research Clinics Study,
researchers reported an independent effect of fitness on all
causes of mortality.26 In this cohort of subjects, higher
quintiles of BMI conferred a higher mortality risk; however,
fitness was more strongly associated than was BMI with
mortality outcomes.
Research suggests that increasing time spent exercising
may not induce weight loss in the short term, but does
prevent the loss of muscle mass. Redman and colleagues27
reported that although exercise represents a favorable
change in energy balance that may result in weight loss,
body composition and fat distribution are similarly affected by
exercise or reduced caloric intake. The authors noted, however,
that exercise has independent salutary effects on cardiovascu-
lar and metabolic outcomes, most likely explaining the data
reported by Lee and colleagues25 correlating improved fitness
level with decreased mortality, regardless of BMI.
Potential Long-Term Impact of Behavior
Modification
Successful weight loss with behavioral therapy that focuses
on lifestyle modification has the potential to improve health
and prevent the progression to type 2 diabetes in vulnerable
individuals. The Diabetes Prevention Program (DPP) Re-
search Group reported that in individuals with glucose in-
tolerance, intensive lifestyle interventions—including a re-
duced-fat and reduced-calorie diet, regular moderate
physical activity, and behavior modification techniques de-
S28
signed to achieve a weight loss goal of 7% of initial body
weight—reduced the incidence of type 2 diabetes by 58%,
compared with a matched control group, after a follow-up
period averaging 2.8 years.28 Furthermore, lifestyle inter-
ventions were substantially more effective than was met-
formin therapy in preventing progression to type 2 diabetes.
A total of 53% of the 3,234 participants enrolled in the
DPP Research Group study had the metabolic syndrome at
baseline, according to the National Cholesterol Education
Program Adult Treatment Panel III (NCEP ATP III). The
NCEP ATP III defines the metabolic syndrome by the
presence of ⱖ3 of the following characteristics: waist cir-
cumference ⬎102 cm (⬎40 in) in men and ⬎88 cm (⬎35
in) in women, serum triglyceride levels ⱖ1.7 mmol/L
(ⱖ150 mg/dL), HDL cholesterol levels ⬍1.03 mmol/L
(⬍40 mg/dL) in men and ⬍1.3 mmol/L (⬍50 mg/dL) in
women, blood pressure of ⱖ130/85 mm Hg, and fasting
plasma glucose levels of ⱖ6.2 mmol/L (ⱖ110 mg/dL).28
Lifestyle intervention was most effective in preventing
the development of the metabolic syndrome in patients not
afflicted with the syndrome at baseline. The 3-year cumu-
lative incidences of the metabolic syndrome were 51%,
45%, and 34% in the placebo, metformin, and lifestyle
groups, respectively. In life table analyses, the incidence of
the metabolic syndrome was reduced by 41% in the lifestyle
group and by 17% in the metformin group, compared with
placebo.28 Resolution of the metabolic syndrome in patients
who met the criteria at baseline was significant between
groups, with the greatest reduction reported in the lifestyle
group. At 3 years, the metabolic syndrome was resolved in
18%, 23%, and 38% of patients in the placebo, metformin,
and lifestyle groups, respectively (P ⬍0.001).28
The Finnish Diabetes Prevention Study Group enrolled
individuals with impaired glucose tolerance to receive no
intervention or an intervention program with a goal of ⱖ5%
weight loss through counseling to reduce fat intake, increase
intake of fiber-rich foods, and engage in 30 minutes of
physical activity daily.4 In findings similar to those reported
by the DPP Research Group, patients receiving lifestyle
intervention had a 58% lower risk of developing type 2
diabetes than did those who received no intervention (P
⬍0.001).4
Can Behavioral Therapy and Lifestyle
Interventions Achieve Long-Term Success?
Behavioral therapy aimed at fostering lifestyle modifica-
tions has been reported as effective in aiding overweight
and obese individuals in achieving weight loss, as well as in
reducing cardiometabolic risk. However, weight regain fol-
lowing weight loss success remains a significant challenge
limiting the benefits of intervention. A review of behavioral
treatment of obesity notes that individuals receiving behav-
ioral therapy for periods of 20 to 30 weeks regained ap-
proximately 30% to 35% of weight initially lost within the
year following treatment.29 Although the rate of weight
The American Journal of Medicine, Vol 122, No 4A, April 2009
regain diminished after the first year, ⱖ50% of individuals
returned to baseline weight within 5 years of treatment.29
Long-term maintenance of lost weight has been exceed-
ingly difficult for many dieters to achieve. Experts point to
overlapping physiologic mechanisms designed to defend
body fat as a survival strategy as 1 major obstacle to long-
term weight loss success.30 Additionally, exposure to an
environment that supports overconsumption of food and
inactivity presents multiple daily challenges for overweight
and obese individuals.31
Long-term behavioral therapy is most likely required to
achieve the lasting benefits of weight loss interventions.
Regular follow-up strategies, including contact through on-
site meetings, telephone calls, mailings, or Internet commu-
nication, have been suggested to improve lasting weight
loss outcome.29
The ongoing Look AHEAD (Action for Health in Dia-
betes) study will better determine the long-term impact of
lifestyle interventions on the rate of serious cardiovascular
events (cardiovascular death, nonfatal myocardial infarc-
tion, and nonfatal stroke) in a population of overweight and
obese individuals with type 2 diabetes.32 Lifestyle interven-
tions consist of reduced-calorie diets, increased physical
activity, and portion-controlled foods; individuals receiving
this intervention strategy will be compared with a control
group receiving diabetes support and education alone. Par-
ticipants will be followed for up to 11.5 years during the
course of the study.
Lifestyle interventions have generally demonstrated the
ability to achieve weight loss of 8% to 10% of initial
weight,33 but lifestyle changes may be most effective when
coupled with pharmacologic treatment to improve weight
loss outcome. A 1-year study of men and women that
compared lifestyle intervention alone (30 group counseling
sessions), sibutramine therapy alone, the combination of
both regimens, and sibutramine plus brief therapy sessions
delivered in the primary care setting found that the combi-
nation of sibutramine and group counseling achieved the
greatest degree of weight loss, averaging 12.1 ⫾ 9.8 kg
(0.45 kg ⫽ 1 lb).6 A study in women likewise found that
sibutramine plus group lifestyle modification sessions
resulted in significantly greater weight loss than did sibu-
tramine alone (P ⬍0.05), and the benefits of this strategy
persisted at 1 year.5 A combination strategy that includes
lifestyle modifications as well as pharmacotherapy could
therefore be a more effective intervention for lasting
weight loss.
Pharmacotherapeutic Strategies for Managing
Overweight and Obesity
The NHLBI Practical Guide suggests that individuals who
already exhibit cardiometabolic risk and have a BMI of 27
to 29.9 may receive pharmacotherapy to aid weight loss
efforts.2 In those without comorbidities, pharmacologic in-
tervention is reserved for those with a BMI ⱖ30. The
Practical Guide emphasizes that pharmacotherapy should
Aronne et al Obesity Treatment Strategies S29

Table 3 Efficacy and safety of weight loss medications

FDA Approval Weight Loss Pooled Data Length of

Medication Year/Intended Use Action (placebo-corrected) Treatment (wk) Common Side Effects
Phentermine 1959/Short-term Sympathomimetic ⫺3.6 kg 7
2-24 7
Palpitations, tachycardia,
weight loss7 amine7 elevated blood
pressure,
gastrointestinal
effects7
Orlistat 1999/Long-term weight Lipase inhibitor7 ⫺2.75 kg7 527 Diarrhea, flatulence,
loss7 bloating7
Sibutramine 1998/Long-term weight Combined ⫺4.45 kg7 527 Increased blood pressure,
loss7 norepinephrine increased pulse, dry
and serotonin mouth, insomnia,
reuptake constipation30
inhibitor7
Bupropion 1985/Antidepressant; Weight loss may ⫺2.77 kg7 24-527 Dry mouth, diarrhea,
smoking cessation30 be due to constipation,
inhibition of insomnia7
norepinephrine
and dopamine
uptake30
Topiramate 1996/Seizure disorder7 Weight loss ⫺6.5%7 247 Paresthesia, taste
mechanism aversion7
unknown30
Zonisamide* 2000/Seizure disorder7 Weight loss ⫺5.0%7 167 Fatigue; small, but
mechanism significant increase in
unknown30 serum creatinine30
Metformin† 1994/Diabetes mellitus Insulin sensitizer; ⫺2.0 kg3,30 14630 Gastrointestinal
suppresses
hepatic glucose
production
*Data obtained from only one trial.
†
Data obtained from the Diabetes Prevention Program Trial; individuals with impaired fasting glucose were treated with drug.
Adapted from N Engl J Med,3 Ann Intern Med,7 and J Clin Endocrinol Metab.30

be used as only 1 aspect of a comprehensive strategy of
behavioral therapy, dietary changes, and increased physical
activity to reduce weight and maintain lost weight.2 The
American Medical Association (AMA) also discourages the
use of pharmacotherapy without supportive lifestyle mod-
ification counseling. Additionally, the AMA suggests that
pharmacotherapy for weight loss should be limited to
agents approved by the US Food and Drug Administra-
tion (FDA).34
Available Pharmacologic Agents. Available pharmaco-
therapy options for overweight and obesity include anorexi-
ants (appetite suppressants) and a lipase inhibitor.2 Anorexi-
ants work to either promote satiety or reduce appetite.
Orlistat is a novel gastric and pancreatic lipase inhibitor that
prevents the absorption of 33% of the fat consumed in
meals.7 The mechanism of action and side-effect profile of
approved weight loss agents are listed in Table 3.3,7,30 The
choice of agent is often limited by the relative ability of the
patient to tolerate anticipated side effects.
Although sibutramine, phentermine, and orlistat are all
approved by the FDA for weight loss, other agents on the
market approved for other uses, such as antidepressants and
drugs used to prevent seizures, have also been shown to
promote weight loss in preliminary clinical trials. However,
these drugs are not approved for weight loss because of lack
of randomized large-scale trials to support their efficacy and
safety.7 In a meta-analysis of agents currently used for
weight loss management, sibutramine, orlistat, and phenter-
mine, as well as the agents bupropion and topiramate, were
shown to promote weight loss for ⱖ6 months, when admin-
istered in conjunction with lifestyle modification.7 The
meta-analysis found that only modest weight loss occurred
with pharmacotherapy, averaging ⬍5 kg at 1 year, but the
authors noted that this weight loss amount may be clinically
significant.
Emerging Therapies. Investigational agents for weight
loss are understandably attractive to both clinicians and
patients because of the difficulty many individuals encoun-
ter in reducing weight and maintaining weight loss. Bupro-
pion and topiramate are approved for other uses and are still
being investigated for their utility in weight loss. Bupropion
is a norepinephrine and dopamine uptake inhibitor that is
S30
approved for use as an antidepressant and smoking cessa-
tion aid.35 Although the drug is not approved for weight
loss, randomized trials have been performed that suggest
a role in weight management; researchers continue to
exhibit interest in determining the relative efficacy and
safety of bupropion compared with that of currently ap-
proved agents.35
Topiramate, a therapy approved for migraine prevention
and the treatment of seizures, has likewise attracted interest
for its potential use in weight management. Most recently,
topiramate, in conjunction with lifestyle modifications, was
found to result in significant weight loss and improved
glucose homeostasis (P ⬍0.001 for both vs. placebo) in
obese, drug-naive subjects with type 2 diabetes. However,
researchers note that the weight loss benefits of topiramate
must be balanced against the potential for central nervous
system side effects.36
Exenatide. Exenatide is a novel incretin mimetic that has
been approved by the FDA for adjunctive therapy to im-
prove glycemic control in patients with type 2 diabetes.
Exenatide is an injectable medication taken twice daily
before mealtime and has been demonstrated to improve
glucose regulation and promote weight loss in patients with
type 2 diabetes.37 In 2 randomized, placebo-controlled 30-
week trials of exenatide in participants with type 2 diabetes,
Riddle and coworkers37 reported that adjunctive treatment
with exenatide reduced glycosylated hemoglobin (A1C) as
well as body weight (–1.4 and –2.1 kg for 5 ␮g and 10 ␮g
bid, respectively, at 30 weeks).37 In open-label extensions
of these studies in which all patients received exenatide 10
␮g bid, weight loss was progressive (⫺4.0 kg ) over 82 weeks
of treatment. Another analysis of the extension study data at 2
years similarly reported that adjunctive exenatide resulted in
progressive reductions in weight and sustained reductions of
A1C, as well as improvements in blood pressure and liver
enzymes.38 Side effects noted with exenatide therapy were
mild-to-moderate nausea and hypoglycemia.37,38
Combination Strategies. Combination pharmacotherapy
regimens that address the cardiometabolic risks of over-
weight and obesity while inducing reasonable weight loss
may represent a new strategy for long-term management.
Research is also addressing the effects of established treat-
ments for hypertension, dyslipidemia, and type 2 diabetes
and their relative ability to support weight loss achieved
with concomitant therapy in obesity. Scholze and associ-
ates39 reported that in a population of obese, hypertensive
patients, a combination antihypertensive regimen consisting
of angiotensin-converting enzyme inhibitors and calcium
channel blockers was more effective than was a combina-
tion ␤-blocker and diuretic regimen in supporting weight
loss in patients also receiving sibutramine. The authors
concluded that these findings may prompt further research
on the specific effects of different therapeutic combinations
in obesity and may guide future evidence-based treatment
recommendations for overweight and obesity.
The American Journal of Medicine, Vol 122, No 4A, April 2009
Cannabinoid Receptor Antagonist (rimonabant). The
endocannabinoid system has been investigated as a novel
therapeutic pathway to target to manage weight in over-
weight and obese individuals.40 Endocannabinoids are li-
gands that are produced and degraded endogenously and
activate the endocannabinoid system through coupling at
specific receptor sites. To date, cannabinoid receptor–1
(CB1) and cannabinoid receptor–2 have been identified and
cloned. CB1 receptors appear to influence energy and appe-
tite regulation, as well as glucose and lipid metabolism.40
Preliminary animal studies demonstrated that endocannabi-
noid levels increase with food deprivation,41 and exposure
to endocannabinoids increases food intake.42 Furthermore,
mice lacking CB1receptors were leaner and consumed less
food.43,44 Exposure to increased levels of endocannabinoids
increased food intake in rats, and this effect was reversed with
the administration of an investigational CB1 receptor blocker
(rimonabant), highlighting the role that the CB1receptor plays
in feeding signals.45
Subsequent clinical trials have supported the role of
CB1receptor antagonism in appetite reduction, weight loss,
and the reduction of cardiometabolic risk factors. In a random-
ized, double-blind, placebo-controlled study reported by
Pi-Sunyer and associates,46 the administration of a CB1receptor
antagonist (rimonabant) effectively reduced weight (– 6.3
kg with 20 mg rimonabant vs. –1.6 kg with placebo;
P ⬍0.001) and waist circumference (– 6.1 cm with 20 mg
rimonabant vs. –2.5 cm with placebo; P ⬍0.001) in over-
weight and obese patients over a period of 2 years. Further-
more, rimonabant administration was associated with ben-
eficial changes in HDL cholesterol (12.6% increase with
rimonabant vs. 5.4% increase with placebo; P ⬍0.001) and
triglycerides (5.3% reduction with rimonabant vs. 7.9%
increase with placebo; P ⬍0.001). The magnitude of car-
diometabolic risk factor reduction was much greater than
would be expected from weight loss alone. The researchers
hypothesized that administration of a CB1 receptor blocker
has a direct effect on glucose and lipid metabolism beyond
the ability to reduce food intake and achieve weight loss. A
similar 1-year trial conducted primarily at European sites
reported similar findings in support of rimonabant.47
In another trial targeting a population of high-risk over-
weight or obese individuals with drug-naive dyslipidemia,
rimonabant administration resulted in substantial weight
loss, reduced waist circumference, increased HDL choles-
terol levels, and reduced triglyceride concentrations.48
Rimonabant was also associated with favorable changes in
LDL particle size, adiponectin levels, glucose tolerance,
insulin levels, and plasma C-reactive protein concentrations,
as well as a decrease in the proportion of individuals meeting
the NCEP ATP III criteria for the metabolic syndrome.
The safety and efficacy of rimonabant treatment in over-
weight and obese individuals with type 2 diabetes was
investigated in a 1-year, randomized, placebo-controlled
trial in adults on monotherapy for diabetes control.49 In
addition to significant declines in weight and waist circum-
ference, and favorable changes in lipid profile, participants
Aronne et al Obesity Treatment Strategies
receiving rimonabant experienced a significant 0.7%, pla-
cebo-corrected reduction in A1C levels, when compared
with the placebo group.
Rimonabant therapy has been associated with mood dis-
orders, including anxiety and depression. The Rimonabant
in Obesity (RIO)–North America trial reported higher rates
of depression and anxiety in patients treated with rimon-
abant at doses of 5 mg/day or 20 mg/day than in placebo-
treated patients, but anxiety and depression scores were
similar between the groups over 2 years of treatment.46 In
the RIO-Europe study, discontinuation rates due to anxiety
were higher in patients receiving rimonabant 20 mg/day
than in those receiving rimonabant 5 mg/day or placebo.47
Another randomized, placebo-controlled trial of 1-year ther-
apy with rimonabant 5 mg/day, rimonabant 20 mg/day, or
placebo likewise reported a higher rate of discontinuation
due to adverse effects, including anxiety, in patients receiv-
ing rimonabant 20 mg/day.48 Therefore, the use of rimon-
abant may be limited in clinical practice, particularly in
patients with preexisting depression.50
SUMMARY
Obesity is a major public health concern and requires ef-
fective treatment strategies to reduce cardiometabolic risk
factors that can lead to substantial morbidity and early mor-
tality. Although strategies exist to achieve modest weight loss
that can substantially reduce cardiometabolic risk, many
individuals continue to be resistant to long-term weight loss.
Challenges persist in achieving and sustaining weight loss in
obese individuals. Individualizing weight loss plans, use of
meal replacements, and increased exercise seem to show im-
provement in outcome measurements. Current data suggest
that combining behavior modification and pharmacotherapy in
treating obese individuals may offer better outcomes than does
either modality alone. Novel therapeutic strategies may be
available in the future that will offer hope to patients combat-
ing obesity.
AUTHOR DISCLOSURES
The authors who contributed to this article have disclosed
the following industry relationships:
Louis J. Aronne, MD, has received financial support for
research from Amylin Pharmaceuticals, Inc, Glaxo-
SmithKline, Medtronic, Inc, Merck & Co, Inc, Obecure
Ltd, Orexigen Therapeutics, Inc, Pfizer Inc, sanofi-aven-
tis Pharmaceuticals, Inc, and Transneuronix, Inc; is a
consultant for Manhattan Pharmaceuticals, Inc, Meta-
bolic Therapeutics, Inc, and sanofi-aventis Pharmaceu-
ticals, Inc; is a member of a Speakers’ Bureau for Pfizer
Inc and sanofi-aventis Pharmaceuticals, Inc; and has
received grant support or consulted for Arena Pharma-
ceuticals, Inc, GI Dynamics, Johnson & Johnson, Novo
Nordisk, TransTech Pharma, Inc, and Vivus Inc.
Thomas Wadden, PhD, is a consultant for Abbott
Laboratories.
S31
Kathy Keenan Isoldi, MS, RD, CDE, has no relevant
financial relationships with a commercial entity produc-
ing healthcare-related products and/or services.
Kristina A. Woodworth has no relevant financial relation-
ships with a commercial entity producing healthcare-
related products and/or services.
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Supplement issue

An Obesity/Cardiometabolic Risk Reduction Disease

Management Program: A Population-Based Approach
Victor G. Villagra, MD
Ethel Donaghue Center for Translating Research into Practice and Policy at the University of Connecticut Health Center, Farmington,
Connecticut, USA; and Health & Technology Vector, Inc., Hartford, Connecticut, USA

ABSTRACT

Obesity is a critical health concern that has captured the attention of public and private healthcare payers
who are interested in controlling costs and mitigating the long-term economic consequences of the obesity
epidemic. Population-based approaches to obesity management have been proposed that take advantage of
a chronic care model (CCM), including patient self-care, the use of community-based resources, and the
realization of care continuity through ongoing communications with patients, information technology, and
public policy changes. Payer-sponsored disease management programs represent an important conduit to
delivering population-based care founded on similar CCM concepts. Disease management is founded on
population-based disease identification, evidence-based care protocols, and collaborative practices between
clinicians. While substantial clinician training, technology infrastructure commitments, and financial
support at the payer level will be needed for the success of disease management programs in obesity and
cardiometabolic risk reduction, these barriers can be overcome with the proper commitment. Disease
management programs represent an important tool to combat the growing societal risks of overweight and
obesity.
© 2009 Elsevier Inc. All rights reserved. • The American Journal of Medicine (2009) 122, S33–S36

KEYWORDS: Cardiometabolic risk; Chronic care model; Disease management; Obesity; Population-based

There is increasing concern among employers about the
adverse cost and productivity impact of the obesity epi-
demic. In the United States, the impact of obesity on the
cost of care among Medicare beneficiaries has also received
attention. A study conducted by the RAND Corporation
predicted that medical innovation will result in a healthier
population that lives longer but will likely also result in
increased Medicare spending because beneficiaries will be
accumulating costs over a longer period.1 The study con-
cludes that improving treatments for chronic diseases, or
even eliminating some chronic diseases, will not mitigate
the projected increase in costs. However, obesity may be an
important exception because, unlike other common chronic
conditions, obesity results in a 40% increase in disability
and a 35% higher cost, without a concomitant reduction in
life expectancy, among 70-year-old beneficiaries compared
Statement of author disclosure: Please see the Author Disclosures
section at the end of this article.
Requests for reprints should be addressed to Victor G. Villagra, MD,
674 Prospect Ave, Hartford, CT 06105.
E-mail address: victor.villagra@snet.net
with their nonobese counterparts.1 This suggests that reduc-
ing the number of obese patients reaching Medicare age
could result in significant savings.
Although there is a general understanding that the obe-
sity epidemic is the result of a complex interaction of social,
behavioral, and economic factors and that solutions will
also require a broad array of strategies, the “medical prob-
lem” of obesity presents itself to healthcare professionals as
a distinct management challenge. As employers become
aware of the adverse health and economic burden of obesity,
requests for effective interventions amenable to large-scale,
“population-based” deployment are becoming more com-
mon. There is a growing body of evidence demonstrating
which components of disease management programs are
most effective2; however, the complex, multifactorial nature
of obesity poses unique challenges. Any sustainable pro-
gram designed to address obesity and reductions in related
health risks will require a well-coordinated plan—an orga-
nization of care capable of reaching tens of thousands of
individuals and a suitable financial base to deliver it cost-
effectively. This article outlines the ideal conditions for the

0002-9343/$ -see front matter © 2009 Elsevier Inc. All rights reserved.
doi:10.1016/j.amjmed.2009.01.006
S34
development of an obesity/cardiometabolic risk reduction
disease management program, its necessary components,
and the role of patients, providers, and payers in such an
effort.
THEORETICAL FRAMEWORK
The chronic care model (CCM)3 provides a useful theoret-
ical framework for a population-based solution to the obe-
sity epidemic, and disease management offers an efficient
operational platform to put it into effect on a large scale.
Disease management is a unique expression of the CCM
and an innovative strategy for the diffusion of evidence-
based interventions across large, geographically dispersed
populations.4,5 The components of the CCM include patient
self-care, community-based resources, continuity of care
beyond traditional sites of care using telephonic and other
forms of communication, information technology, decision
support tools for patients and providers, delivery system
redesign, and enabling public policy (Figure 1).3 The ele-
ments of disease management include population-based
identification methods, evidence-based contents, collabora-
tive relationships with physicians, and ongoing evaluation
and feedback to patients, providers, and payers (Figure 2).6
BARRIERS AND OPPORTUNITIES FOR AN
OBESITY/CARDIOMETABOLIC RISK REDUCTION
DISEASE MANAGEMENT PROGRAM
A number of barriers to an effective obesity/cardiometa-
bolic risk reduction disease management program can be
identified; however, solutions are also emerging.
At the Physician Practice Level
Physicians report a number of barriers to effective manage-
ment of obesity. Cited barriers include a lack of time to
address obesity during routine office visits, a lack of reim-
bursement for these services,7 a sense that obesity is a
chronic disease with high recidivism rates, and inadequate
training and lack of training mechanisms for physicians in
the medical management of obesity. The CCM provides a
helpful template for practice redesign that would eventually
overcome some of those barriers, but transforming physi-
cian practices would represent a lengthy process that is out
of step with the sense of urgency that the obesity epidemic
represents. A more desirable approach would be a col-
laborative arrangement between existing payer-sponsored
disease management programs and individual physician
practices. Such an arrangement would offer multiple advan-
tages,8 including shortening the time required to deploy
large-scale programs.9
The solution to the perceived gap of physician low self-
efficacy would be the development of effective obesity/
cardiometabolic risk reduction physician-training vehicles.
The knowledge base for effective treatments across the entire
continuum of therapeutic alternatives spanning behavior mod-
ification, pharmacotherapy, and bariatric surgery is avail-
The American Journal of Medicine, Vol 122, No 4A, April 2009
able and expanding rapidly. Use of Web-based distance-
learning technology and case-based training are examples of
recent advances in the science of knowledge transfer.
At the Payer Level
Appropriate financial support for an obesity/cardiometa-
bolic risk reduction initiative is needed. An increasingly
popular mechanism for potentially stimulating behavior
change is physician pay-for-performance.10 Some programs
are stimulating the management of isolated cardiometabolic
risks, such as hypertension, dyslipidemia, and tobacco use,
but those efforts must be coordinated and expanded so that
efforts converge in a patient-centric direction rather than
persist as isolated, risk-oriented initiatives. A logical next
step would be to stimulate better management of overweight
and obesity. An obesity/cardiometabolic risk reduction dis-
ease management program could catalyze and expand cur-
rent pay-for-performance efforts to encompass all of the
elements of the metabolic syndrome. Financial benefits
would accrue to physicians, and patients would realize clin-
ical benefits. However, it remains to be seen whether the
RAND study suggestion that obesity prevention efforts will
translate into cost savings for payers is correct.
At a Population Level
A systematic, population-based identification of at-risk in-
dividuals is critical for the success of any disease manage-
ment program.10 To that end, clinicians develop patient
registries11 at the point of service, and payers query their
claims databases.12,13 Traditional lack of reimbursement for
obesity-related services has discouraged use of obesity In-
ternational Classification of Diseases–9th Revision (ICD-9)
codes in claims submission. Use of codes identifying the
metabolic syndrome also is very infrequent. For these
reasons, cost-effective identification of obesity/cardiometa-
bolic risk reduction program candidates using administra-
tive databases is not possible. Alternative means of patient
identification are needed. Examples include increased use of
health risk assessment by employers and insurance compa-
nies, development of patient self-referral mechanisms, and
expansion of practice-based patient registries. A coordi-
nated, collaborative effort between payers and providers
could combine strategies to identify and electronically reg-
ister large numbers of obese individuals amenable to disease
management programs in a relatively short period.8
WHAT WILL AN OBESITY/CARDIOMETABOLIC
RISK REDUCTION DISEASE MANAGEMENT
PROGRAM OFFER TO PATIENTS?
An obesity/cardiometabolic risk reduction disease manage-
ment program can offer patients a variety of concrete ben-
efits. Specifically:
● Information: Disease management programs provide pa-
tients with information about their condition and its treat-
ment. The information is of the highest scientific quality,
but it is presented in simple-to-understand lay terms.
Villagra Obesity Disease Management Program S35

The Chronic Care Model

Health System
Community
Health Care Organization
Resources and
Policies
Self-Management Delivery Decision Clinical
Support System Support Information
Design Systems

Informed,
Activated Patient
Supportive, Prepared,
Integrated Productive Interactions Proactive
Community Practice Team

Figure 1 The chronic care model of healthcare delivery. (Adapted from Health Aff
(Millwood).3)

Disease Management

24-Hour
Claims Eligibility Provider Rx Lab HRA/QOL UM Health
Advice

Population-Based Patient identification

Population-based patient Identification
Interventions Interventions
Available Risk Stratification Applied

Mild Moderate Severe

Care
Management
Workstation
Figure 2 Components of the disease management concept of healthcare delivery. HRA ⫽
health risk assessment; Lab ⫽ laboratory; QOL ⫽ quality of life; Rx ⫽ prescriptions; UM ⫽
utilization. (Adapted from the Disease Management Association of America.6)

● Self-care skills: Disease management promotes greater ● Motivation: Care managers— highly trained nurses and
control and independence in patients by encouraging de- other clinicians who interact regularly with patients, usu-
velopment of their self-care skills, including self-moni- ally over the phone—provide a source of ongoing patient
toring practices such as use of food diaries. motivation to adopt healthful lifestyles.
S36
● Support: Care managers actually support patients through
their efforts to quit smoking, increase physical activity
levels, adhere to diets, and manage their stress.
● Self-efficacy: Through repetition, attainment of short-term
realistic goals, and encouragement, patients attain pro-
gressively higher levels of self-efficacy. Perception of
self-efficacy is among the strongest predictors of success
in lifestyle modification.
● Self-care tools: Disease management programs provide
tools for self-care, such as scales for patients with con-
gestive heart failure, blood pressure cuffs for patients
with hypertension, and, for individuals with access to
computers, software for tracking and transmitting key
information to their physicians.
● Visit planning: Care managers provide visit-planning
coaching so that patients are able to maximize the value
of each physician visit. Physicians also benefit from more
effective and efficient patient visits.
PROGRAM LEADERSHIP AND COORDINATION
Under the guidance of physicians, an obesity/cardiometa-
bolic risk reduction program would provide ongoing patient
self-care education and support—a critical component for
long-term success of obesity/cardiometabolic risk reduction
treatment plans. Program contents would be supported by
the best-available scientific evidence. This approach has
been shown to improve adherence to behavioral and phar-
macologic treatment plans among patients with chronic con-
ditions. In many cases, it has been shown to reduce use of
the emergency room and hospital admissions and to lower
overall cost of care.14,15 These performance indicators align
well with employers expectations.
SUMMARY
The implementation of comprehensive obesity/cardiometa-
bolic risk reduction disease management programs faces
barriers that can be readily overcome. Disease management
programs can result in a wider adoption of evidence-based
treatments, a significant reduction in long-term treatment
failures, and potentially lower overall costs of care. A co-
ordinated disease management initiative would represent a
sensible response to employers’ and other payers’ demands
for action.
AUTHOR DISCLOSURES
The author of this article has disclosed the following indus-
try relationships:
The American Journal of Medicine, Vol 122, No 4A, April 2009
Victor G. Villagra, MD, is a member of the Board of
Directors of Genomas, Inc, a consultant for Healthways,
Inc, and sanofi-aventis Pharmaceuticals, Inc, and an
independent contractor for the Disease Management As-
sociation of America.
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Gano A Jr, et al. Interventions used in disease management pro-
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livery system during and after managed care. Health Aff (Millwood).
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11. Wagner EH, Grothaus LC, Sandhu N, et al. Chronic care clinics for
diabetes in primary care: a system-wide randomized trial. Diabetes
Care. 2001;24:695-700.
12. Koroukian SM, Cooper GS, Rimm AA. Ability of Medicaid claims
data to identify incident cases of breast cancer in the Ohio Medicaid
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13. Solz H, Gilbert K. Health claims data as a strategy and tool in disease
management. J Ambul Care Manage. 2001;24:69-85.
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266.
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Does diabetes disease management save money and improve out-
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684-689.
 Supplement to
The American Journal of Medicine

The Obesity Epidemic: Strategies in Reducing

Cardiometabolic Risk

CME SECTION
ASSESSMENT TEST

Provided by:

Release Date: April 2009 Expiration Date: April 30, 2010

CME ASSESSMENT TEST
The Obesity Epidemic: Strategies in Reducing Cardiometabolic Risk

Please circle the correct response to each question on c. Abstinence from alcohol
the Answer Sheet provided. A passing score of ⱖ70% d. Regular exercise regimen
must be achieved to receive CME credit.
7. In a trial conducted by the Diabetes Prevention
1. Approximately what percentage of Americans are Program Research Group that studied a popula-
currently classified as overweight or obese based on tion of individuals with elevated fasting glucose,
body mass index (BMI)? which of the following interventions had the
a. 30% greatest impact on lowering the risk of develop-
b. 25% ing type 2 diabetes:
c. 66% a. Metformin therapy
d. 75% b. Lifestyle interventions that achieved weight loss
2. The use of which assessment tool may be helpful in c. Weight loss medications
assessing health risks in individuals evaluated for d. Exercise alone
overweight and obesity?
a. BMI 8. Which of the following hormone levels increase(s)
b. Waist circumference proportionately with body fat?
c. Waist-to-hip ratio a. Leptin
d. All of the above b. Insulin
c. a and b
3. In its definition of the metabolic syndrome, a joint d. Cholecystokinin
statement by the American Heart Association and
the National Heart, Lung, and Blood Institute sug- 9. Which of the following organs or tissues produces
gested that the threshold for ______ be reduced inflammatory cytokines that have been linked to
from the threshold identified by the National Cho- insulin resistance and cardiovascular risk?
lesterol Education Program Adult Treatment Panel a. Liver
III (NCEP ATP III) to more accurately capture b. Small intestine
diabetic risk. c. Adipose tissue
a. Triglycerides d. Kidney
b. Fasting blood glucose
c. Abdominal obesity 10. As defined by the NCEP ATP III, the metabolic
d. Hypertension syndrome includes all of the following traits except:
a. Elevated waist circumference
4. Both the San Antonio Heart Study and a large popu- b. Elevated fasting triglyceride levels
lation-based study of familial type 2 diabetes found c. Decreased high-density lipoprotein cholesterol
that the metabolic syndrome is associated with an levels
increased risk of important health effects, including: d. Increased low-density lipoprotein cholesterol
a. Stroke levels
b. Myocardial infarction
c. All-cause mortality 11. The 2005 US Department of Agriculture (USDA)
d. All of the above Dietary Guidelines for Americans suggests that
5. Abnormal lipid metabolism is a manifestation of those with a target diet of 2,000 calories per day
obesity and increases the risk of: should consume:
a. Cardiovascular events a. 1 cup fruits, 2 cups vegetables
b. Gout b. 5 or more daily servings of fruits
c. Diabetes c. 9 or more daily servings of fruits and vegetables
d. Inflammation d. 4 or more daily servings of fruits and vegetables

6. In a study of female nurses followed over a period
of 16 years, which trait did not contribute to lower
risk of type 2 diabetes:
a. Maintenance of BMI ⱕ25
b. High-fiber, low-fat, low-glycemic-load diet
12. Rolls et al demonstrated that which of the following
factors significantly correlated with the amount of
one type of food consumed during a meal?
a. The amount of food offered
b. The perceived palatability of the food

April 2009 THE AMERICAN JOURNAL OF MEDICINE姞 Vol 122 (4A) S43
 c. The individual’s perceived hunger prior to meal
initiation
d. The caloric content of the food
13. Which of the following dietary changes in the
American population has been linked to rising obe-
15. The National Heart, Lung, and Blood Institute
sity rates in recent decades?
a. Increased fat content of food
b. Increased fruit and vegetable consumption
c. Increased sodium content of food
d. Increased consumption of dairy products
14. In a meta-analysis by Nordmann et al, which dietary
strategy was able to more effectively sustain weight
loss over 12 months?
a. Low-fat diet
b. Low-carbohydrate diet
S44 April 2009 THE AMERICAN JOURNAL OF MEDICINE姞 Vol 122 (4A)
c. There was no difference between the 2 diets at
12 months
d. Neither diet achieved measurable weight loss at
12 months
Practical Guide suggests considering the addition
of pharmacotherapy to an otherwise comprehensive
strategy of behavioral therapy, dietary changes, and
increased physical activity to induce weight loss in
individuals falling within which of the following
groups?
a. BMI of 27 to 29.9 with comorbidities
b. BMI ⱖ30
c. All individuals with a BMI ⱖ25
d. a and b
--------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
CME ASSESSMENT TEST ANSWER SHEET

The Obesity Epidemic: Strategies for Reducing Cardiometabolic Risk

Instructions for Continuing Medical Education Credit:
This activity should take approximately 4.0 hours to complete. To receive AMA PRA Category 1 Credits™ for your
participation in this educational activity, you must complete both the posttest and the evaluation form. The
participants should review the educational objectives listed in the front of this supplement to determine if the content
relates to their individual learning needs. They should read the supplement carefully, paying particular attention to
the tables and other illustrative materials, and then circle the best answer for each of the 15 multiple-choice posttest
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credit for this activity, follow the instructions provided on the posttest. Credit is valid through April 30, 2010. No
credit will be given after that date.
Mail completed posttest and evaluation to:

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Or fax to: 312-464-5841, attn: Obesity CME Coordinator

ANSWER SHEET (circle the best answer to each question)

1. a b c d 4. a b c d 7. a b c d 10. a b c d 13. a b c d
2. a b c d 5. a b c d 8. a b c d 11. a b c d 14. a b c d
3. a b c d 6. a b c d 9. a b c d 12. a b c d 15. a b c d

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CME Evaluation Form
The Obesity Epidemic: Strategies in Reducing Cardiometabolic Risk
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