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N 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 publisher (Humana Press, c/o Springer Science + Business Media, LLC, 233 Spring Street, New York, NY 10013, USA), except for brief excerpts in connection with reviews or scholarly analysis. Use in connection with any form of informa- tion storage and retrieval, electronic adaptation, computer software, or by similar or dissimilar methodology now known or hereafter developed is forbidden. The use in this publication of trade names, trademarks, service marks, and similar terms, even if they are not identified as such, is not to be taken as an expression of opinion as to whether or not they are subject to proprietary rights. While the advice and information in this book are believed to be true and accurate at the date of going to press, neither the authors nor the editors nor the publisher can accept any legal responsibility for any errors or omissions that may be made. The publisher makes no warranty, express or implied, with respect to the material contained herein. Printed on acid-free paper springer.com 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.

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