Table Of ContentN M
UTRITION AND ETABOLISM
Nutrition and Health
Adrianne Bendich, PhD, FACN, Series Editor
For other titles published in this series, go to
www.springer.com/series/7659
N
UTRITION
M
AND ETABOLISM
Underlying Mechanisms
and Clinical Consequences
Editor
Christos S. Mantzoros, MD, DSc
Division of Endocrinology, Diabetes and Metabolism,
Beth Israel Deaconess Medical Center, Harvard Medical School,
Boston, MA, USA
Editor
Christos S. Mantzoros, MD, DSc
Division of Endocrinology
Diabetes and Metabolism
Beth Israel Deaconess Medical Center
Harvard Medical School
Boston, MA
USA
Series Editor
Adrianne Bendich, PhD, FACN
GlaxoSmithKline Consumer Healthcare
Parsippany, NJ
USA
ISBN: 978-1-60327-452-4 e-ISBN: 978-1-60327-453-1
DOI: 10.1007/978-1-60327-453-1
Library of Congress Control Number: 2009922619
© Humana Press, a part of Springer Science+Business Media, LLC 2009
All rights reserved. This work may not be translated or copied in whole or in part without the written permission of the
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Dedication
To my parents, whose lifelong service to their suffering fellow human beings became
a true inspiration and enlightened guidance for my professional and personal life
Series Preface
The Nutrition and HealthTM series of books have, as an overriding mission, to pro-
vide health professionals with texts that are considered essential because each includes:
(1) a synthesis of the state of the science, (2) timely, in-depth reviews by the leading
researchers in their respective fi elds, (3) extensive, up-to-date fully annotated reference
lists, (4) a detailed index, (5) relevant tables and fi gures, (6) identifi cation of paradigm
shifts and the consequences, (7) virtually no overlap of information between chapters,
but targeted, inter-chapter referrals, (8) suggestions of areas for future research, and
(9) balanced, data-driven answers to patient/health professionals questions which are
based upon the totality of evidence rather than the fi ndings of any single study.
The series volumes are developed to provide valuable in-depth information to nutrition
health professionals and health providers interested in practical guidelines. Each editor
has the potential to examine a chosen area with a broad perspective, both in subject mat-
ter as well as in the choice of chapter authors. The international perspective, especially
with regard to public health initiatives, is emphasized where appropriate. The editors,
whose trainings are both research and practice oriented, have the opportunity to develop
a primary objective for their book, defi ne the scope and focus, and then invite the leading
authorities from around the world to be part of their initiative. The authors are encouraged
to provide an overview of the fi eld, discuss their own research, and relate the research
fi ndings to potential human health consequences. Because each book is developed de
novo, the chapters are coordinated so that the resulting volume imparts greater knowledge
than the sum of the information contained in the individual chapters.
Nutrition and Metabolism: Underlying Mechanisms and Clinical Consequences, edited
by Christos S. Mantzoros, MD is a very welcome addition to the Nutrition and Health
Series and fully exemplifi es the Series’ goals. This volume is especially timely since
the obesity epidemic continues to increase around the world and the comorbidities, such
as the metabolic syndrome, type II diabetes, hypertension, and hyperlipidemia are seen
even in very young children. The editor reminds us that, for most people, their weight
remains relatively stable despite wide variations in the types of foods we consume each
day, differences in caloric content, and differences in daily physical activity. It is only
recently that physicians, scientists, and health providers have begun to think about the
complexities of excess body weight. This volume contains informative chapters that
look at the genetics associated with obesity, the role of the nervous system and the
endocrine system, the gastrointestinal tract and of great importance, adipose tissue,
as more than a fat storage site. The last decade has seen an explosion of identifi cation
vii
viii Series Preface
and characterization of the many bioactive molecules that are synthesized and secreted
by adipose cells (adipokines). The adipokines and other molecules synthesized in the
stomach, intestines, pancreas, and other gastrointestinal organs have been associated
with the development of obesity and its comorbidities as well as many, often thought of
as unrelated, consequences including insulin resistance, cardiovascular complications,
lipid disorders, hypertension, and hormonal imbalances as examples. Thus, the relevance
of obesity-related pathophysiology to the clinical setting is of great interest to not only
academic researchers, but also healthcare providers. This text is the fi rst to synthesize
the knowledge base concerning obesity and its comorbidities including metabolic syn-
drome, diabetes, hypertension, and hyperlipidemia, and relate these to the mechanisms
behind the alterations in metabolism that increase chronic disease risk. This unique
volume also contains practice guidelines and tools for obesity management to help the
practicing health professional as well as those professionals who have an interest in the
latest, up-to-date information on obesity treatments and their implications for improving
human health and reducing obesity-related diseases.
This volume serves the dual purposes of providing current clinical assessment and
management guidelines as well as relevant background information on the genetics and
pathophysiology associated with the consequences of obesity. The chapters include an
historic perspective as well as suggestions for future research opportunities. Dr. Mant-
zoros is an internationally recognized leader in the fi eld of obesity research as well as
clinical outcomes. He and his authors are excellent communicators and he has worked
tirelessly to develop a book that is destined to be the benchmark in the fi eld because
of its extensive, in-depth chapters covering the most important aspects of the complex
interactions between cellular functions, diet and obesity, and its impact on disease states.
The editor has chosen 32 of the most well-recognized and respected authors from around
the world to contribute the 18 informative chapters in the volume. Hallmarks of all of the
chapters include complete defi nitions of terms with the abbreviations fully defi ned for the
reader and consistent use of terms between chapters. Key features of this comprehensive
volume include the informative key points and keywords that are at the beginning of each
chapter, appendices that include detailed tables of major nutrient recommendations for
weight reduction in the obese as well as for those with diabetes; detailed descriptions
of the Dietary Approaches to Stop Hypertension (DASH) diet protocol; an extensive list
of foods and their glycemic index and many other practical guidelines to help in patient
management. The volume also contains more than 80 detailed tables and informative
fi gures, an extensive, detailed index, and more than 2,000 up-to-date references that
provide the reader with excellent sources of worthwhile information about the role of
diet, exercise, food intake, physiology and pathophysiology of obesity, the metabolic
syndrome, types I and II diabetes, and other obesity-related comorbidities.
Dr. Mantzoros has coauthored many of the chapters and he has chosen chapter authors
who are internationally distinguished researchers, clinicians, and epidemiologists who
provide a comprehensive foundation for understanding the role of weight control in the
maintenance of human health as well as its role in obesity and related co-morbidities.
The book is organized into logical sections that provide the reader with an overview of
the complexities of weight control. There is an extensive discussion of the genetics of
obesity and the involvement of at least 11 human genes in the control of food intake and
metabolism. Genetically linked obesity syndromes are described including Prader–Willi
Series Preface ix
syndrome. This chapter includes new information on the genetics of metabolic syndrome,
types I and II diabetes and reviews the fi ndings that link these diseases genetically. The
interaction between the central and peripheral nervous systems, the endocrine system, and
molecules synthesized during digestion are discussed in the next chapter that introduces
the reader to the concepts of metabolic signals, orosensory stimuli, GI tract peptides
and adipokines from fat tissue. Explanations are provided for the role of leptin, insulin,
peptide YY, ghrelin, visfatin, cholecystokinin, and many other important modulators
in human metabolism. An important chapter is devoted to the description of the central
nervous system with detailed explanations of the importance of the hypothalamus and
the brain stem. We learn that control of appetite resides in the arcuate nucleus area of the
hypothalamus, whereas the paraventricular nucleus is involved with energy homeostasis.
This chapter reviews the importance of orexigenic and anorexigenic neuropeptides as
well as the effects of thyroid hormones, adrenergic receptors, and thermogenic tissues.
The fi nal chapter in the section on genetics and pathophysiology looks at insulin resis-
tance and its consequences. The concept of adipose tissue infl ammation is introduced
and there is discussion about body fat distribution including the effects of visceral vs.
subcutaneous fat.
Childhood obesity is a major public health concern as the percentage of young children
that are obese or overweight continues to grow globally. There is an extensive review of the
published studies that have attempted to control weight gain in children and adolescents
most of which do not use pharmacological agents. Certainly, more research is needed in
this area as long-term successful strategies have not been developed and well-accepted
guidelines for clinical practice are not currently available. Two chapters review recom-
mendations for diet and physical activity for healthy adults in one chapter and for the
prevention and management of diabetes in the other chapter. These chapters discuss the
importance of reducing trans fats, total fat, refi ned grains, and sugar-sweetened bever-
ages. The authors review the data on the importance of physical activity to help control
lipid levels and improve energy balance. The fi nal chapter in this section examines
the association of obesity and cancer risk. Poor dietary habits account for about 35%
of incident cancers and smoking accounts for 30%; obesity accounts for 15%. About
16–20% of cancer deaths in US women and 14% in US men can be attributed to obesity.
The chapter includes an analysis of the dietary habits around the globe that can result in
a sevenfold difference in the rates of breast and prostate cancers between Western type
diets and the rates seen in Japan.
Many nations have developed nutrition recommendations for the general population as
well as for those individuals who suffer from the co-morbidities associated with obesity
including diabetes and cardiovascular disease. This section of the volume considers the
guidance that has been provided, reviews the history of the development of US national
dietary guidelines and the most recent Food Guide Pyramid, and follows with a provoca-
tive chapter by Drs. Willett and Stampfer that questions the scientifi c basis for some
of the more general national recommendations given in the Pyramid. Nutrition recom-
mendation for those with cardiovascular disease includes reduction of salt, saturated and
trans fats and increases in dietary fi ber, antioxidants, B vitamins, omega-3 fatty acids,
mono-unsaturated fatty acids, calcium, and potassium. Examples of food-based interven-
tion studies that have reduced cardiovascular disease (CVD) risk factors including the
prudent diet, DASH diet, Mediterranean diet and the guidelines from the American Heart
x Series Preface
Association and the European Society of Cardiology are discussed in detail. Details are
also provided for the assessment of cardiovascular disease including the biochemical
markers currently used to stage the patient. This chapter also discussed the role of dietary
supplements in CVD management. In the past 20 years, a new fi eld of patient care has
emerged called medical nutrition therapy (MNT). MNT has been particularly important
in the management of patients with types I and II diabetes. Practice guidelines have been
developed for children, adolescents, and adults and have been of value in the control of
blood glucose levels as well as glycosylated hemoglobin. Diets are recommended that
contain levels of essential micronutrients important to the diabetic. This chapter and the
additional information in the related appendices provide practical information for the
health provider. There is also a separate chapter that describes the Mediterranean diet
and the clinical studies, including survey data, case–control and intervention studies that
have examined the potential for this diet to reduce obesity and CVD.
The fi nal section includes in-depth chapters on the clinical assessment and manage-
ment of obesity and its co-morbidities. There is a comprehensive chapter on lifestyle
and pharmacological treatments for obesity. It is of interest that even today that hyper-
cholesterolemia remains undiagnosed in 50% of the US population and 95% remain
undertreated. This chapter explains the effects of hypertension, often seen in the obese,
on carotid medial intimal thickness and the clinical studies that have included treat-
ments. A comprehensive review of statin use is also included. Accurate diagnosis tools
for obesity and diabetes are provided in the next chapter and also include management
tools for gestational diabetes. Another informative chapter describes the use of bariatric
surgery and the critical importance of the preoperation evaluation. We are reminded that
to date weight loss surgery is the only effective treatment for severe, medically com-
plicated, and refractory obesity. Guidelines for patient inclusion, types of operations,
and importantly, postoperation care are provided in detail. The fi nal chapter reviews the
major co-morbidities associated with obesity and weight loss due to bariatric surgery
that have not been included in other chapters. These areas include the increased risk of
osteoporosis and fracture following bariatric surgery and the increased risk of gallstones
that also occurs after this surgery. On the other hand, there appears to be a signifi cant
decrease in mortality as well as a decrease in sleep apnea and osteoarthritis. The lit-
erature on the increased risk of certain cancers with obesity is also included. Each of
the chapter authors has integrated the newest research fi ndings so the reader can better
understand the complex interactions that can result from excess weight gain as well as
loss of excess weight.
Given the growing concern with the increase in adult as well as childhood obesity, it
is not surprising to fi nd that all chapters in this valuable book are devoted to the clinical
aspects of obesity, weight control, diabetes, and other chronic diseases associated with
obesity. Moreover, both the cultural aspects of weight gain and the emotional triggers
of eating are reviewed. Emphasis is also given to the growing awareness that obesity is
associated with a low-grade infl ammatory state. The editor and authors have integrated
the information within these chapters so that the healthcare practitioner can provide guid-
ance to the patient about the potential consequences of chronic obesity. The inclusion of
both the earlier chapters on the complexity of human physiology and the chapters that
contain clinical discussions helps the reader to have a broader basis of understanding
of obesity and the attendant co-morbidities.
