Contents

Robert B. Tattersall

K. George M.M. Alberti

Lars C. Stene, Valma Harjutsalo, Elena Moltchanova & Jaakko Tuomilehto

Ronald C.W. Ma & Peter C.Y. Tong

Mohammed K. Ali, Mary Beth Weber & K.M. Venkat Narayan

Peter M. Jones & Shanta J. Persaud

Xuxia Wu & W. Timothy Garvey

George A. Bray

Ahmed J. Delli, Helena Elding Larsson, Sten-A. Ivarsson & Ake Lernmark

Alice P.S. Kong & Juliana C.N. Chan

Mazen Alsahli & John E. Gerich

Hannele Yki-Jarvinen

Martine Vaxillaire & Philippe Froguel

Adrian Vella & Robert A. Rizza

Hans Hauner

Angus Jones & Andrew T. Hattersley

Neil J.L. Gittoes, John Ayuk & Robin E. Ferner

Neil A. Hanley

Ranjit Unnikrishnan & Viswanathan Mohan

Ee Lin Lim & Roy Taylor

Richard I.G. Holt & Barry J. Goldstein

Carole Mensing & Barbara Eichorst

Monika Toeller

Jane E. Yardley, Angela Alberga, Glen P. Kenny & Ronald J. Sigal

Brian M. Frier & Mark W.J. Strachan

Andrew J. Farmer

Bernard M.Y. Cheung & Robin E. Ferner

Stephen Gough & Parth Narendran

Howard Wolpert & Judy Shih

Clifford J. Bailey & Andrew J. Krentz

Jens Juul Holst, Sten Madsbad & Ole Schmitz

Joseph A. Aloi & Anthony L. McCall

Maggie Sinclair Hammersley & June James

Philip E. Cryer

Troels Krarup Hansen & Niels Møller

Ferdinando Giacco & Michael Brownlee

Peter H. Scanlon

Sally M. Marshall & Allan Flyvbjerg

Dan Ziegler

Riccardo Candido, Mark E. Cooper & Karin A.M. Jandeleit-Dahm

Peter M. Nilsson

Adie Viljoen & Anthony S. Wierzbicki

Inga S. Thrainsdottir & Lars Ryden

Colum F. Amory & Jesse Weinberger

Henrik H. Sillesen

Andrew J.M. Boulton

David Price

Adil E. Bharucha & Michael Camilleri

Graham R. Sharpe & Paul D. Yesudian

Andrew Grey & Nicola Dalbeth

Christopher M. Ryan

Clive S. Cockram & Nelson Lee

Christine Chan & Marian Rewers

Debbie Kralik & Maria Kambourakis

Anne Dornhorst & Anita Banerjee

Alan J. Sinclair

Robert C. Peveler & Richard I.G. Holt

Jane Overland, Margaret McGill & Dennis K. Yue

Wing-Yee So & Juliana C.N. Chan

Naomi S. Levitt, Bob Mash, Nigel Unwin, Jean Claude Mbanya, Jae-Hyoung Cho & Kun-Ho Yoon

Helena Elding Larsson, Ahmed J. Delli, Sten-A. Ivarsson & Ake Lernmark

Clifford J. Bailey

Shuibing Chen, Jayaraj Rajagopal, Qiao Zhou & Douglas A. Melton

Angela Koh, Peter Senior & A.M. James Shapiro

Andreea R. Barbu & Nils Welsh

Robert A. Gabbay & Alan M. Adelman

We dedicate this book to all people living with diabetes and the healthcare professionals who look after them. We would also like to dedicate this book to our families without whose support and encouragement the book would never have been finished.

This edition first published 2010. © 1991, 1997, 2003, 2010 by Blackwell Publishing Ltd

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ISBN: 9781405191814

A catalogue record for this book is available from the British Library.

Library of Congress Cataloging-in-Publication Data

Textbook of diabetes. – 4th ed./ edited by Richard I.G. Holt … [et al.]. p.; cm.

Includes bibliographical references and index.

ISBN 978-1-4051-9181-4 (hardback : alk. paper)

1. Diabetes. I. Holt, Richard I.G.

[DNLM: 1. Diabetes Mellitus. WK 810 T355 2010]

RC660.T467 2010

616.4’62–dc22

2010013907

List of Contributors

Alan M. Adelman MS, MD

Professor of Family and Community Medicine, Vice Chair for Academic Affairs and Research, Penn State Milton S. Hershey Medical Center, Penn State College of Medicine, Hershey, PA, USA

Angela Alberga MSc

Faculty of Health Sciences, University of Ottawa and Ottawa Hospital Research Institute, Ottawa, Ontario, Canada

K. George M.M. Alberti DPhil, FRCP

Senior Research Fellow, Imperial College, London; Emeritus Professor of Medicine, University of Newcastle, Newcastle, UK

Mohammed K. Ali MBChB, MSc

Assistant Professor, Hubert Department of Global Health, Rollins School of Public Health, Global Diabetes Research Center, Emory University, Atlanta, GA, USA

Joseph A. Aloi MD

Associate Professor of Internal Medicine, The Strelitz Diabetes Center for Endocrine and Metabolic Disorders, Eastern Virginia Medical School, Norfolk, VA, USA

Mazen Alsahli MD

Professor of Medicine, University of Rochester School of Medicine, Rochester, NY, USA

Colum F. Amory MD, MPH

Mount Sinai School of Medicine, New York, NY, USA

John Ayuk MD

Centre for Endocrinology, Diabetes and Metabolism, University of Birmingham and Queen Elizabeth Hospital Birmingham, Birmingham, UK

Clifford J. Bailey PhD, FRCP(Edin), FRCPath

Professor in Clinical Science and Head of Diabetes Research, School of Life and Health Sciences, Aston University, Birmingham, UK

Anita Banerjee BSc, MBBS, MRCP

Obstetric Physician, Diabetes and Endocrinology, Princess Royal University Hospital, London, England UK

Andreea R. Barbu PhD

Department of Medical Cell Biology and Department of Medical Sciences, Uppsala University, Uppsala, Sweden

Adil E. Bharucha MD

Professor of Medicine, Division of Gastroenterology and Hepatology, Clinical Enteric Neuroscience Translational and Epidemiological Research Program, Mayo Clinic, Rochester, MN, USA

Andrew J.M. Boulton MD, DSc (Hon), FRCP

Professor of Medicine, University of Manchester and Manchester Royal Infirmary, Manchester, UK; Miller School of Medicine, University of Miami, Miami, FL, USA

George A. Bray MD, MACP

Boyd Professor, Pennington Biomedical Research Center, Louisiana State University, Baton Rouge, LA, USA

Michael Brownlee MD

Anita and Jack Saltz Professor of Diabetes Research, Albert Einstein College of Medicine, New York, NY, USA

Michael Camilleri MD

Atherton and Winifred W. Bean Professor, Professor of Medicine and Physiology, College of Medicine, Mayo Clinic and Clinical Enteric Neuroscience Translational and Epidemiological Research Program, Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN, USA

Riccardo Candido MD, PhD

Diabetic Centre, Trieste, Italy

Christine M. Chan MD

Barbara Davis Center for Childhood Diabetes, University of Colorado Denver, School of Medicine, Aurora, CO, USA

Juliana C.N. Chan MBChB MD FRCP

Professor of Medicine and Therapeutics, Director, Hong Kong Institute of Diabetes and Obesity, The Chinese University of Hong Kong, The Prince of Wales Hospital, Hong Kong SAR, China

Shuibing Chen PhD

Postdoctoral Fellow, Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA, USA

Bernard M.Y. Cheung MD, PhD

Chair of Clinical Pharmacology and Therapeutics, Department of Clinical Pharmacology, University of Birmingham, Birmingham, UK

Jae-Hyoung Cho MD

Assistant Professor, Department of Endocrinology, Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea

Mark E. Cooper MD, PhD

Director, Danielle Alberti JDRF Centre for Diabetes Complications, Head, Vascular Division – Baker IDI Heart Research Institute, Melbourne, Australia

Philip E. Cryer MD

Irene E. and Michael M. Karl Professor of Endocrinology and Metabolism in Medicine, Washington University School of Medicine, St. Louis, MO, USA

Nicola Dalbeth MD, FRACP

Department of Medicine, University of Auckland, Auckland, New Zealand

Ahmed J. Delli MD, MPH

Clinical Research Center (CRC), Lund University, Department of Clinical Sciences/Diabetes and Celiac Disease, University Hospital MAS, Malmö, Sweden

Anne Dornhorst BSc, DM, FRCP, FRCPath

Consultant Physician, Honorary Senior Lecturer, Department of Medicine, Imperial College Healthcare NHS Trust, Hammersmith Hospital, London, UK

Barbara Eichorst MS,RD,CDE

Healthy Interactions Global Conversation Map™ Facilitator, Chicago, IL, USA

Andrew J. Farmer DM, FRCGP

University Lecturer, Department of Primary Health Care, University of Oxford, Oxford, UK

Robin E. Ferner MSc, MD, FRCP

Professor, West Midlands Centre for Adverse Drug Reactions, City Hospital, Birmingham, UK

Brian M. Frier BSc(Hons), MD, FRCPE, FRCPG

Professor, Department of Diabetes, Royal Infirmary of Edinburgh, Edinburgh, UK

Philippe Froguel MD, PhD

Institut de Biologie de Lille, Institut Pasteur de Lille, Lille, France; Section of Genomic Medicine, Imperial College London, London, UK

Robert A. Gabbay MD, PhD

Director, Penn State Institute for Diabetes and Obesity; Professor of Medicine and Molecular Medicine, Penn State College of Medicine; Director, Diabetes Program, Penn State Milton S. Hershey Medical Center, Hershey, PA, USA

W. Timothy Garvey MD

Butterworth Professor and Chair, Department of Nutrition Sciences; Director, UAB Diabetes Research and Training Center, University of Alabama at Birmingham; Birmingham Veterans Affairs Medical Center, Birmingham, AL, USA

John E. Gerich MD

Professor of Medicine, University of Rochester School of Medicine, Rochester, NY, USA

Ferdinando Giacco PhD

Postdoctoral Fellow, Diabetes Research and Training Center, Departments of Medicine and Endocrinology, Albert Einstein College of Medicine, New York, NY, USA

Neil J.L. Gittoes MD

Senior Lecturer in Medicine, Centre for Endocrinology, Diabetes and Metabolism, University of Birmingham and Queen Elizabeth Hospital Birmingham, Birmingham, UK

Steve Gough

Professor of Diabetes, Oxford Centre for Diabetes Endocrinology and Metabolism, University of Oxford; Consultant Physician, Churchill Hospital, Oxford, UK

Andrew Grey MD

Department of Medicine, University of Auckland, Auckland, New Zealand

Maggie Sinclair Hammersley MB, FRCP

Consultant Physician and Senior Lecturer, Nuffield Department of Medicine, University of Oxford, Oxford, UK

Neil A. Hanley MBChB, PhD

Professor of Medicine, Endocrinology and Diabetes Group, University of Manchester, Manchester, UK

Troels Krarup Hansen MD, PhD

Associate Professor, Department of Endocrinology and Internal Medicine, Aarhus University Hospital, Aarhus, Denmark

Valma Harjutsalo PhD

Folkhälsan Institute of Genetics, Folkhälsan Research Center, Biomedicum Helsinki; Diabetes Prevention Unit, National Institute of Health and Welfare, Helsinki, Finland; Division of Nephrology, Department of Medicine, Helsinki University Central Hospital, Helsinki, Finland

Andrew T. Hattersley MD

Diabetes and Vascular Medicine, Peninsula Medical School, Exeter, UK

Hans Hauner MD

Director, Else Kröner-Fresenius-Center for Nutritional Medicine, Klinikum rechts der Isar, Technical University of Munich, Munich, Germany

Jens Juul Holst MD, DMSc

Professor of Medical Physiology, Department of Biomedical Sciences, The Panum Institute, University of Copenhagen, Denmark

Sten–A. Ivarsson MD, PhD

Clinical Research Center (CRC), Lund University and Department of Clinical Sciences/Paediatric Endocrinology, University Hospital MAS, Malmö, Sweden

June James MSc, BA (Hons) Dip Nursing, NP RGN

Consultant Nurse in Diabetes, University Hospitals of Leicester, Leicester, UK

Karin A.M. Jandeleit-Dahm MD, PhD, FRACP

Baker IDI Heart and Diabetes Institute, Co-head, Diabetes Division; Professor of Medicine (Adjunct), Monash University, Melbourne, Australia

Peter Jones PhD

Professor of Endocrine Biology, King’s College London, London, UK

Angus Jones MBBS, MRCP

Diabetes and Vascular Medicine, Peninsula Medical School, Exeter, UK

Maria Kambourakis BSc(Hons)

Research Officer/Type 1 Diabetes Program Officer, Type 1 Diabetes Program, Diabetes Australia, Victoria, Australia

Glen P. Kenny MD

Ottawa Hospital Research Institute and Laboratory of Human Bioenergetics and Environmental Physiology, School of Human Kinetics, Faculty of Health Sciences, University of Ottawa, Ottawa, Ontario, Canada

Angela Koh MBBS (Singapore), MRCP (UK)

Assistant Professor, Department of Medicine (Endocrinology), Attending Physician, Clinical Islet Transplant Program, University of Alberta, Edmonton, Canada

Alice P.S. Kong MBChB, MRCP (UK), FRCP (Glasg)

Associate Professor, Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong SAR, China

Debbie Kralik PhD, RN

General Manager, Research and Strategy, Royal District Nursing Service, South Australia; Associate Professor, University of South Australia and University of Adelaide, Glenside, Australia

Andrew J. Krentz MD, FRCP

Formerly Southampton University Hospitals NHS Trust, Southampton, UK

Helena Elding Larsson MD, PhD

Clinical Research Center (CRC), Lund University; Department of Clinical Sciences/Paediatric Endocrinology, University Hospital MAS, Malmö, Sweden

Nelson Lee MD, FRCP(Edin)

Associate Professor, Head, Division of Infectious Diseases, Department of Medicine and Therapeutics, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong SAR, China

Åke Lernmark PhD

Professor of Experimental Diabetes, Lund University/CRC, Department of Clinical Sciences, University Hospital MAS, Malmö, Sweden

Naomi S. Levitt MBChB, MD, FCP(SA)

Professor and Head of Division of Diabetic Medicine and Endocrinology, Department of Medicine, University of Cape Town and Groote Schuur Hospital, Cape Town, South Africa

Ee Lin Lim MRCP

Diabetes Research Group, Institute of Cellular Medicine, University of Newcastle, Newcastle upon Tyne, UK

Ronald C.W. Ma MB BChir, MRCP

Associate Professor, Division of Endocrinology and Diabetes, Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Prince Of Wales Hospital, Hong Kong SAR, China

Sten Madsbad MD, DMSc

Professor of Diabetology, Department of Endocrinology, Hvidovre Hospital, Hvidovre, Denmark

Sally M. Marshall MD

Professor of Diabetes, Diabetes Research Group, Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, UK

Bob Mash MBChB, MRCGP, PhD

Professor, Division of Family Medicine and Primary Care, Stellenbosch University, Tygerberg, South Africa

Jean-Claude Mbanya MD, PhD, FRCP

Professor of Medicine and Endocrinology, Faculty of Medicine and Biomedical Sciences, University of Yaounde I, Yaounde, Cameroon

Anthony L. McCall MD, PhD

James M. Moss Professor of Diabetes in Internal Medicine, Diabetes and Hormone Center of Excellence, University of Virginia School of Medicine, Charlottesville, VA, USA

Margaret McGill RN, MSc(med)

Diabetes Centre, Royal Prince Alfred Hospital, Camperdown, Sydney, New South Wales, Australia

Douglas A. Melton

Thomas Dudley Cabot Professor in the Natural Sciences, Department of Stem Cell and Regenerative Biology; Harvard Stem Cell Institute; Investigator, Howard Hughes Medical Institute, Harvard University, Cambridge, MA, USA

Carolé R. Mensing RN, MA, CDE

Joslin Diabetes Center, Boston, MA, USA

Viswanathan Mohan MD, FRCP(UK), FRCP(Glasg), PhD, DSc, FNASc

Chairman and Chief Diabetologist, Dr. Mohan’s Diabetes Specialities Centre, WHO Collaborating Centre for Non Communicable Diseases Prevention and Control, IDF Centre of Education; President and Chief of Diabetes Research, Madras Diabetes Research Foundation, ICMR Advanced Centre for Genomics of Diabetes, Gopalapuram, Chennai, India

Niels Møller MD, DMSc

Professor, Department of Endocrinology and Internal Medicine, The Medical Research Laboratories, Arhus University Hospital, Arhus, Denmark

Elena Moltchanova PhD

Diabetes Unit, Department of Health Promotion and Chronic Disease Prevention, National Institute for Health and Welfare, Helsinki, Finland

K. M. Venkat Narayan MD, MSc, MBA, FRCP

Ruth and O.C. Hubert Professor of Global Health, Professor of Epidemiology and Medicine, Rollins School of Public Health, Emory University, Atlanta, GA, USA

Parth Narendran

Institute of Biomedical Research, The Medical School, University of Birmingham, Birmingham, UK

Peter M. Nilsson MD

Professor of Clinical Cardiovascular Research, Department of Clinical Sciences, Lund University, University Hospital, Malmö, Sweden

Jane Overland MPH, PhD

Nurse Practitioner, Diabetes Centre, Royal Prince Alfred Hospital, Campderdown, New South Wales, Australia; Clinical Associate Professor, The Faculty of Nursing and Midwifery, The University of Sydney, Sydney, Australia

Shanta J. Persaud PhD

Professor of Diabetes and Endocrinology, King’s College London, London, UK

Robert C. Peveler MA, DPhil, BM, BCh, FRCPsych

Clinical Neurosciences Division, School of Medicine, University of Southampton and Royal South Hants Hospital, Southampton, UK

David Price MD, FRCP

Department of Diabetes and Endocrinology, Morriston Hospital, Swansea, UK

Jayaraj Rajagopal

Center for Regenerative Medicine, Massachusetts General Hospital; Principal Investigator, Harvard Stem Cell Institute, Boston, MA, USA

Marian Rewers MD, PhD

Professor, Pediatrics and Preventive Medicine; Clinical Director, Barbara Davis Center for Childhood Diabetes, University of Colorado Denver, School of Medicine, Aurora, CO, USA

Robert A. Rizza MD

Professor of Medicine, Division of Endocrinology, Diabetes, Metabolism and Nutrition, Mayo Clinic, Rochester, MN, USA

Christopher M. Ryan PhD

Professor of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA

Lars Rydén MD, FRCP, FESC, FACC, FAHA

Professor Emeritus, Cardiology Unit, Department of Medicine, Karolinska Institute, Stockholm, Sweden

Peter H. Scanlon MD, MRCOphth, DCH, FRCP

Consultant Ophthalmologist, Gloucestershire and Oxford Eye Units; Lecturer, Harris Manchester College, University of Oxford, Oxford, UK

Ole Schmitz MD, DMSc

Professor of Clinical Pharmacology, Department of Clinical Pharmacology, Aarhus University Hospital, Denmark

Peter A. Senior BMedSci, MBBS, PhD, MRCP(UK)

Clinical Islet Transplant Program, University of Alberta, Edmonton, Alberta, Canada

A.M. James Shapiro MD PhD DSc (Hon) FRCS(Eng) FRCSC MSM

Professor of Surgery, Director, Clinical Islet Transplant Program, AHFMR Scholar, University of Alberta, Edmonton, Canada

Graham R. Sharpe MBChB, BA, PhD, FRCP

Consultant Dermatologist, Department of Dermatology, Broadgreen Hospital, Liverpool, UK

Judy Shih MD, PhD

Joslin Diabetes Center, Boston, MA, USA

Ronald J. Sigal MD, MPH, FRCPC

Professor of Medicine, Cardiac Sciences, and Community Health Sciences, Faculties of Medicine and Kinesiology, The University of Calgary, Canada

Henrik H. Sillesen MD, DMSc

Head, Department of Vascular Surgery, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark

Alan J. Sinclair MSc, MD, FRCP

Deputy Dean and Professor of Medicine, Bedfordshire and Hertfordshire Postgraduate Medical School; Geriatric and Diabetes Research Centre, University of Bedfordshire, Luton, UK

Wing-Yee So MBChB, MD, FRCP

Associate Consultant, Prince of Wales Hospital, Hong Kong SAR, China

Lars C. Stene PhD

Division of Epidemiology, Norwegian Institute of Public Health, Oslo, Norway; Oslo Diabetes Research Centre, Oslo University Hospital, Oslo, Norway

Mark W. J. Strachan MD, FRCP (Edin)

Consultant in Diabetes and Endocrinology, Metabolic Unit, Western General Hospital, Edinburgh, UK

Robert B. Tattersall MB, ChB, MD, FRCP

Emeritus Professor of Clinical Diabetes, University of Nottingham, Nottinghamshire, UK

Roy Taylor MD, FRCP

Professor of Medicine and Metabolism, and Director, Newcastle Magnetic Resonance Centre, Newcastle University, Newcastle upon Tyne, UK

Inga S. Thrainsdottir MD, PhD

Department of Cardiology, Landspitali University Hospital, Reykjavik, Iceland

Monika Toeller MD

German Diabetes Center, Heinrich Heine University Düsseldorf and Leibniz Center for Diabetes Research, Düsseldorf, Germany

Peter C.Y. Tong MBBS, PhD, BPharm, FRCP

Professor, Division of Endocrinology and Diabetes, Department of Medicine and Therapeutics, The Chinese University of Hong Kong and Prince Of Wales Hospital, Hong Kong SAR, China

Jaakko Tuomilehto MD, MA, PhD

Hjelt Institute, University of Helsinki and Diabetes Prevention Unit, Department of Health Promotion, National Institute for Health and Welfare, Helsinki, Finland, and South Ostrobothnia Central Hospital, Seinäjoki, Finland

Ranjit Unnikrishnan MD

Director and Consultant Diabetologist, Dr. Mohan’s Diabetes Specialities Centre, WHO Collaborating Centre for Non Communicable Diseases Prevention and Control and IDF Centre of Education, Madras Diabetes Research Foundation, ICMR Advanced Centre for Genomics of Diabetes, Chennai, India

Nigel Unwin BA, MSc, DM, FRCP, FFPH

Professor of Public Health and Epidemiology, Faculty of Medicine, University of the West Indies, Barbados

Martine Vaxillaire PharmD, PhD

Research Director at Pasteur Institute, CNRS 8090 and Pasteur Institute, Lille, France

Adrian Vella MD, FRCP(Edin)

Associate Professor of Medicine, Division of Endocrinology, Diabetes, Metabolism and Nutrition, Mayo Clinic, Rochester, MN, USA

Adie Viljoen MBChB, MMed, FCPath (SA), FRCPath, MBA

Consultant Chemical Pathologist, Department of Chemical Pathology, Lister Hospital, Stevenage, UK

Mary Beth Weber MPH

Nutrition and Health Sciences Program, Graduate Division of Biological and Biomedical Sciences, Global Diabetes Research Center, Emory University, Atlanta, GA, USA

Jesse Weinberger MD

Department of Neurology, Mount Sinai School of Medicine, New York, NY, USA

Nils Welsh MD, PhD

Professor in Molecular Inflammation Research, Department of Medical Cell Biology, Uppsala University, Uppsala, Sweden

Anthony S. Wierzbicki DM, DPhil, FRCPath, FAHA

Consultant Metabolic Physician and Chemical Pathologist, Guy’s and St Thomas Hospitals, London, UK

Howard Wolpert MD

Joslin Diabetes Center, Boston, MA, USA

Xuxia Wu MD, PhD

Department of Nutrition Sciences, University of Alabama at Birmingham, Birmingham, AL, USA

Jane E. Yardley MSc

Faculty of Health Sciences, University of Ottawa and Ottawa Hospital Research Institute, Ottawa, Ontario, Canada

Paul D. Yesudian MB, MD, MRCP

Consultant Dermatologist, Department of Dermatology, University of Liverpool and Broadgreen Hospital, Liverpool, UK

Hannele Yki-Järvinen MD, FRCP

Professor of Medicine, Department of Medicine, Division of Diabetes, University of Helsinki, Helsinki, Finland

Kun-Ho Yoon MD, PhD

Professor, Department of Endocrinology and Metabolism, Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea

Dennis K. Yue MBBS, FRACP, PhD

Diabetes Centre, Royal Prince Alfred Hospital; University of Sydney, Sydney, New South Wales, Australia

Qiao Zhou

Assistant Professor, Department of Stem Cell and Regenerative Biology, Principle Investigator, Harvard Stem Cell Institute, Havard University, Cambridge, MA, USA

Dan Ziegler MD, FRCPE

Professor of Internal Medicine, Institute for Clinical Diabetology, German Diabetes Center at the Heinrich Heine University, Leibniz Center for Diabetes Research; Department of Metabolic Diseases, University Hospital, Düsseldorf, Germany

Preface to the Fourth Edition

The management of diabetes is a major health challenge, and its prevalence is increasing at an alarming rate, especially in the developing world. According to the International Diabetes Federation, diabetes currently affects more than 285 million people worldwide, a figure that is expected to rise to 435 million by 2030. During the writing of this book over the last 18 months, approximately 15 million people will have developed diabetes. Although treatments continue to improve, many people die as a result of their diabetes. Between 6–16% of all deaths are attributable to diabetes and around 900 will have died in the 2 hours taken to write this preface. Diabetes accounts for about 6% of total global mortality, on a par with that seen in HIV/AIDS. Many of these deaths will result from cardiovascular disease which occurs at least twice as often in diabetes as in people without diabetes. Diabetes continues to cause suffering through its complications. It is the commonest cause of kidney failure in developed countries where it is also the leading cause of blindness in adults of working age. Diabetes is also a major cause of non-traumatic lower limb amputation. As well as the personal cost, diabetes places a huge burden on health economies. In 2010, it is estimated that worldwide, at least US$ 376 billion will be used to treat and prevent diabetes and its complications. Never have the challenges in providing diabetes healthcare been larger.

During the eight years since the publication of the previous edition of this textbook, there have been great strides in the management and understanding of diabetes. International collaborations using large and varied cohorts with increasingly sophisticated technologies have allowed a greater appreciation of the genetic factors that predispose to diabetes. Our molecular understanding of insulin resistance and the regulation of insulin secretion has increased as has our appreciation of the mechanisms underlying complications.

The diagnostic criteria look set to be changed again and may incorporate hemoglobin A1c (HbA_1c) while the units of the latter have also recently changed to reflect the development of more reliable and traceable assays. As HbA_1c remains the currency of everyday diabetes practice, these changes will provide major educational challenges for patients and professionals alike.

Alongside the developments in the pathophysiology of diabetes have come major advances in the treatment of diabetes. Some of these therapeutic innovations have been withdrawn, such as inhaled insulin, but many have been adopted in clinical practice. The development of new oral agents to treat type 2 diabetes has diversified choices for clinicians and people with diabetes. Drugs affecting glucagon-like peptide 1 (GLP-1) and the incretin axis that were mentioned briefly as future treatments in the last edition are now firmly established as effective treatments of type 2 diabetes. Many studies have highlighted the advantages and disadvantages of the newer agents making the choice of treatment more complicated than ever. Beyond the gluco-centric view of diabetes, major cardiovascular trials continue to show the benefits of statin therapy in people with diabetes.

The publication of this new edition is timely given the rapid advances in knowledge. This edition has a new editorial team drawn from the UK, Europe, USA and Asia to reflect the global nature of the diabetes epidemic. The new team has experienced a big learning curve and we are profoundly grateful that we could stand on the shoulders of John Pickup and Gareth Williams, the editors of the previous three editions. The new book has retained many of the excellent author team brought together by John and Gareth and the structure is similar to the previous editions. Nevertheless like any new teams we have tried to improve the book while keeping the sound ideas from the previous book. The book has been shortened into one volume to make it easier to use. We have emphasized the clinical aspects of diabetes to a greater extent than previous editions and reflecting the diverse locations of the editors, the chapter authors are also dispersed throughout the globe making this a truly international textbook which crosses continents and highlights both developed and developing health systems.

As editors we are only too aware of the work that many people have contributed to the book, without which our endeavors would have been much harder, if not impossible. The chapter authors are at the top of our list for our gratitude. Their willingness to devote their time and effort into compiling scholarly and relevant chapters, while tolerating nagging e-mails from us, has been humbling. In an age where book writing often comes fourth behind grant and paper writing and clinical work, we are grateful for the way that the authors met the deadlines set by us. We are also grateful for the immense help we have received from our publisher, Wiley-Blackwell. Our Commissioning Editor Oliver Walter, who took over from Alison Brown shortly into the book’s development, has provided encouragement, support and guidance as has Jennifer Seward, the Development Editor. Often just at the time when things appeared to be insurmountable, Oliver or Jennifer took steps to get the project moving again. Our thanks also go to Rob Blundell (Production Editor) and Helen Harvey (Project Manager) in the production team.

We hope you enjoy reading the book and find it useful whether this is helping people with diabetes or teaching physicians and other health professionals how best to manage this disease and its complications.

Richard I.G. Holt
Clive S. Cockram
Allan Flyvbjerg
Barry J. Goldstein

Foreword

The face of diabetes is forever changing. Scientific knowledge increases exponentially and our understanding slowly improves although there are still massive gaps in many fundamental aspects of the diabetes story, such as the mechanisms underlying the development of type 2 diabetes. Trying to keep up with all the advances is an ever increasing burden, but with a large array of means to achieve this. Many people use the web, both specific websites and more general search engines, but there are still a large number of people who prefer the printed word and the collection together of an accessible compendium where you can expect to obtain answers to your questions. This volume provides exactly that; namely a series of up-to-date, well referenced, learned articles covering the manifold manifestations of diabetes together with the basic underlying science. It is truly comprehensive and I would challenge any reader to find missing aspects of the pathophysiology, treatment and care of people with diabetes.

The book begins with a fascinating historical essay which should be read by anybody who picks up the book. It reminds us that much valuable information is forgotten and many lessons can be learned by going back to pre-internet days! The possibility of using HbA_1c for the diagnosis of diabetes is discussed reflecting a potentially seismic shift in our diagnostic armamentarium that has relied on the measurement of glucose since that became available routinely a century ago. The world pandemic of diabetes is described with few populations spared and then each type of diabetes is described together with what is known of their pathophysiology. Particularly valuable are the essays on non-classical type 1 and type 2 diabetes.

The management and treatment of diabetes from education through lifestyle modification and the use of oral agents and insulin is dealt with exhaustively with useful chapters on the oft ignored psychological and social aspects of the disorder. Different models of care are also well discussed. Complications are dealt with comprehensively and again the book is of particular value in going beyond the classical complications and dealing with a range of less well defined problems found in people with diabetes. The book finishes with crystal ball gazing: a look at future drugs for both type 1 and type 2 diabetes, as well as the potential for stem cell therapy, islet cell transplantation and gene therapy, all of which are thought provoking and informative.

Overall I feel that this volume fulfils a major need for anyone with an interest in diabetes; it should be available in every setting where people with diabetes receive their care and will serve as an excellent vade mecum.

K. George M.M. Alberti
Imperial College London

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