Joslin's Diabetes Mellitus

1235 Pages·2005·33.112 MB·English

by  Kahn, C. Ronald;Joslin, Elliot P

Joslin’s
Diabetes Mellitus
Fourteenth Edition

Joslin’s
Diabetes Mellitus
Fourteenth Edition
Edited by
C. Ronald Kahn, M.D. Gordon C. Weir, M.D.
PRESIDENT AND DIRECTOR, HEAD OFTHE SECTION ON ISLETTRANSPLANTATION
JOSLIN DIABETES CENTER; AND CELL BIOLOGY AND DIABETES RESEARCH
MARY K. IACOCCA PROFESSOR OF MEDICINE, AND WELLNESS FOUNDATION
HARVARD MEDICAL SCHOOL, CHAIR, JOSLIN DIABETES CENTER;
BOSTON, MASSACHUSETTS PROFESSOR OF MEDICINE,
HARVARD MEDICAL SCHOOL,
BOSTON, MASSACHUSETTS
George L. King, M.D. Alan M. Jacobson, M.D.
DIRECTOR OF RESEARCH AND HEAD OFTHE SENIORVICE PRESIDENT, STRATEGIC INITIATIVES DIVISION,
SECTION ONVASCULAR CELL AND HEAD OFTHE BEHAVIORAL
BIOLOGY, JOSLIN DIABETES CENTER; AND MENTAL HEALTH UNIT,
PROFESSOR OF MEDICINE, JOSLIN DIABETES CENTER;
HARVARD MEDICAL SCHOOL, PROFESSOR OF PSYCHIATRY,
BOSTON, MASSACHUSETTS HARVARD MEDICAL SCHOOL,
BOSTON, MASSACHUSETTS
Alan C. Moses, M.D. Robert J. Smith, M.D.
FORMER CHIEF MEDICAL OFFICER, DIRECTOR OF MEDICINE ANDTHE HALLETT CENTER FOR
JOSLIN DIABETES CENTER; DIABETES AND ENDOCRINOLOGY,
PROFESSOR OF MEDICINE (ON LEAVE), PROFESSOR OF MEDICINE,
HARVARD MEDICAL SCHOOL, BROWN MEDICAL SCHOOL,
BOSTON, MASSACHUSETTS PROVIDENCE, RHODE ISLAND
ASSOCIATEVICE PRESIDENT OF MEDICAL AFFAIRS,
NOVO NORDISK PHARMACEUTICALS INC.,
PRINCETON, NEW JERSEY
Acquisitions Editor:Lisa McAllister
Developmental Editor: Joyce Murphy
Manufacturing Manager:Angela Panetta
Production Service: Nesbitt Graphics, Inc., Bonnie Boehme/Marilyn Dwyer
Director, Medical Production:Charlene Catlett Squibb
Compositor:Nesbitt Graphics, Inc.
Printer:Quebecor World–Taunton
© 2005 by JOSLIN DIABETES CENTER
One Joslin Place
Boston, MA02215
joslin.org
All rights reserved. This book is protected by copyright. No part of this book may be reproduced inany form
or by any means including photocopy or recording, or utilized by any information storage andretrieval system
without written permission from the copyright owner, except for brief quotations embodied in critical articles
and reviews.
Printed in the USA
Library of Congress Cataloging-in-Publication Data
Joslin, Elliott Proctor, 1869-1962.
Joslin's diabetes mellitus.-- 14th ed. / edited by C. Ronald Kahn ... [et
al.].
p. cm.
Includes bibliographical references and index.
ISBN 0-7817-2796-0
1. Diabetes. I. Title: Diabetes mellitus. II. Kahn, C. Ronald. III.
Title.
RC660.J6 2005
616.4'62--dc22
2004025662
Care has been taken to confirm the accuracy of the information presented and to describe generally accepted
practices. However, the editors, authors and publisher are not responsible for errors or omissions or for any
consequences from application of the information in this book and make no warranty, express or implied, with
respect to the currency, completeness, or accuracy of the contents ofthe publication. Application of this
information in a particular situation remains the professional responsibility of the practitioner.
The editors, authors and publisher have exerted every effort to ensure that drug selection and dosage set forth
in this text are in accordance with current recommendations and practice at the time of publication. However, in
view of ongoing research, changes in government regulations, and the constant flow of information relating to
drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any change in
indications and dosage and for added warnings and precautions. This is particularly important when the
recommended agent is a new or infrequently employed drug.
Some drugs and medical devices presented in this publication have Food and Drug Administration (FDA)
clearance for limited use in restricted research settings. It is the responsibility of the health care provider to
ascertain the FDAstatus of each drug or device planned for use in clinical practice.
10 9 8 7 6 5 4 3 2 1
Preface
We are pleased to present this 14th edition of Joslin’s Diabetes Patients come to Joslin and its affiliated institutions from all
Mellitus. This textbook continues to evolve and address the over the world, knowing that whatever problems they have can
newest and most important insights into this very old but very be addressed by someone who understands the full complexity
challenging disease. Indeed, as this book goes to press, despite of diabetes. Thus, the Joslin staff consists of adult and pediatric
multiple medical and scientific advances, we are facing a diabetologists, nephrologists, ophthalmologists and optome-
worldwide epidemic of diabetes. This involves a steady increase trists, and mental health professionals, as well as nurse educa-
in type 1 diabetes and almost an exponential increase in type 2 tors and nutrition specialists. Problems in vascular disease, car-
diabetes. The latter is accompanied by a parallel increase in diology, neurology, and in virtually all other areas of medicine,
obesity, the metabolic syndrome, and other closely related dis- are now managed in collaboration with colleagues at the Beth
orders. Thus we are at a fascinating point in the evolution of Israel Deaconess Hospital (BIDMC). Women with diabetes
diabetes and a fascinating point in the evolution of a book also receive coordinated care between Joslin and BIDMC, and
devoted to this disease. sick children often are hospitalized at Children’s Hospital
The first edition of the Joslin textbook was published in Boston.
1916, a single-handed contribution by a man of extraordinary To meet the challenges of the epidemic of diabetes, Joslin
dedication, vision, and energy, Dr. Elliott P. Joslin. Dr. Joslin has established Affiliated Centers with 22 sites throughout the
began his practice in 1898 in the pre-insulin era, and in this United States and our first international Affiliate in Bahrain.
setting, developed a unique understanding of the natural his- Because there are experts at these institutions who have exten-
tory of diabetes. This perspective was clearly evident in the first sive experience in virtually every aspect of diabetes care, some
edition, which was published some five years before the dis- have joined with Joslin staff to write the clinical chapters,
covery of insulin by Banting, Best, Macleod, and Collip. describing the characteristics and outcomes of their patients in
The third edition, published in 1923 shortly after the dis- the context of the broader literature.
covery of insulin, showed how quickly Joslin grasped the prin- Research has always been a fundamental focus at Joslin and
ciples of insulin therapy, adopting approaches that would be as such has been reflected in all of the editions. Dr. Joslin him-
considered modern even by today’s standards. As a student of self was a fine clinical investigator who made astute observa-
metabolism, Dr. Joslin was unwavering in his conviction that tions about his patients and recorded the information in
blood glucose levels should be kept as close to normal as pos- meticulous fashion, as can be appreciated in his numerous
sible, even though the importance and even the existence of publications. He also recognized the need for a more organized
chronic complications of diabetes were not appreciated until approach to research and appointed Dr. Alexander Marble as
many years later. He understood the critical role of education the first head of research in 1934. The research programs were
for people with diabetes and made it the cornerstone of all greatly expanded when Dr. Albert Renold took over the lead-
treatment programs. His insights into the interaction between ership in 1957, and further enhanced under the leadership of
diet, exercise, and glucose control were also remarkable, con- George Cahill, Stuart Soeldner, C. Ronald Kahn, and now
sidering how difficult it was to assess control accurately at this George King.
time. His descriptions of the symptoms of hypoglycemia are as Thus, the most recent editions of Joslin’s Diabetes Mellitus,
well defined as can be found anywhere today, and he rapidly including the current edition, reflect not only the practice and
determined the small quantity of carbohydrate required to experiences of the physicians of the Joslin Diabetes Center, but
treat insulin reactions. Any serious student of diabetes should also the remarkable body of new scientific information that has
spend time with these early editions. had such an impact on the field. In addition, we have called
The evolution of the Joslin textbook mirrors the develop- upon former fellows and trainees of Joslin, now numbering
ment of the field of diabetes and in some ways the development over 1,200, and our academic colleagues elsewhere, to help
of Joslin Diabetes Center. Although the book was originally present the latest advances in basic and clinical research.
written entirely by Dr. Joslin himself, in subsequent editions he The 14th edition is very different from the 13th edition
included his colleagues in the task, taking advantage of their spe- published a decade ago. These differences demonstrate the dra-
cial expertise. Eventually, substantial contributions to the book matic advances in knowledge and research. Progress in the
were provided not only by the staff of Joslin Diabetes Center, basic sciences has been explosive in recent years, particularly in
but also by clinicians from the adjacent New England Deaconess the areas of immunology, insulin signaling, cell and molecular
Hospital, where most Joslin patients were hospitalized. biology, and genetics. This has resulted in a remarkable
vi PREFACE
increase in our understanding of the basic processes underlying During his tenure, Dr. Bradley also edited the Joslin text-
type 1 and type 2 diabetes, as well as diabetes complications. book, gave numerous lectures, and served on the first National
Because of this rapid rate of new knowledge, this text, like Diabetes Advisory Board from 1977 to 1980. Bob retired in
all modern biomedical texts, must be considered a living doc- 1987 and died on October 12, 2003. He will always be
ument, subject to change and updated regularly. Every reason- remembered as a soft-spoken, highly dedicated leader and for
able effort has been made to have the 14th edition closely the wonderful legacy he left for Joslin and people with diabetes
reflect our current understanding of diabetes. throughout the world.
Inaddition, while less emphasis has been given to the local Second, we dedicate this 14th edition of Joslin’s Diabetes
Joslin experience in describing various aspects of diabetes care Mellitus to all of the patients with diabetes and their families
and more effort has been made to incorporate the experiences who have allowed us to care for them over the 106-year history
of others described in the literature, an effort has been made to of the Joslin Diabetes Center. They are the reason for our exis-
retain the flavor of Joslin’s clinical strategies and the emphasis tence and the inspiration for working even harder. They
on the importance of the team approach. inform our search for knowledge and our efforts to improve
The Joslin Diabetes Center stands today as an institution the lives of people with diabetes across the globe.
on the front lines of the world epidemic of diabetes, leading We also dedicate this 14th edition of Joslin’s Diabetes Melli-
the battle to conquer diabetes in all of its forms through tusto all of those who have so generously supported Joslin with
cutting-edge research and innovative approaches to clinical their efforts and funds to support research, clinical care, and
care and education. Our task, of course, is to realize our vision education. Without that support, the institution could not
of a world without diabetes and its complications. Dissemi- survive and continue to work toward the cure, prevention, and
nating the most current diabetes research and approaches to improved treatment of diabetes and its complications.
care is part of our vision and mission. Last, we wish to thank all of the individuals who worked
This 14th edition of Joslin’s Diabetes Mellitusis dedicated to together to bring this book to fruition. The authors of the var-
a number of special individuals—first, to Dr. Robert F. Bradley, ious chapters spent untold hours thinking, researching, and
who arrived at Joslin in 1950 as a young clinician fresh out of writing to reach the level of excellence expected of a book of
the Navy. By 1968, he had become the Medical Director of the this stature. Two individuals, with whom it has been a pleasure
Joslin Clinic, and in 1977, he became President of the fully to work, have made great contributions to the project. Susan
integrated Joslin Diabetes Center. Under his leadership, Joslin Sjostrom, the Director of Publications at Joslin, was remark-
grew steadily in both its clinical and research missions. ably efficient at keeping track of all the manuscripts, disks, cor-
Perhaps Dr. Bradley’s most significant contribution was his respondence and e-mail. Nancy Voynow, the editorial assistant
role in a major controversy of the mid-1970s over the use of in Boston, was thoroughly professional, skilled, and efficient
oral drugs in the treatment of diabetes. A large NIH-funded throughout, doing a wonderful job editing this enormous
study, the UGDP, suggested that the available oral agents for amount of complicated material. We also greatly appreciate the
diabetes, the sulfonylureas, might not be safe. In fact, the study efforts and skill of our publisher, Lippincott Williams &
suggested that these agents might cause more deaths by pro- Wilkins.
ducing certain cardiovascular side effects than they saved And, of course, most of all, we thank our families for their
through treatment of diabetes. Dr. Bradley found this conclu- support and tolerance of the never-ending intrusion of this
sion contrary to his own experience with thousands of patients book into evenings, weekends, and at times even vacations.
with diabetes, and so he challenged this study, not just quietly
and privately, but loudly and in the public eye. Consequently Boston, Massachusetts
the UGDP study was found to be seriously flawed, and thus C. Ronald Kahn
sulfonylureas, very important drugs for the treatment of type 2 Gordon C. Weir
diabetes, remained on the market. As a result, millions of George L. King
patients with diabetes have benefited from improved diabetes Alan M. Jacobson
control. Alan C. Moses
Robert J. Smith
Contributors
Martin J. Abrahamson, MD, Maha T. Barakat, MBBChir, MA, MRCP, Lisa M. Bolduc-Bissell, RN, CDE,
Acting Chief Medical Officer, PhD, Diabetes Nurse Clinician,
Joslin Diabetes Center; Honorary Consultant, Endocrinology, Department of Endocrinology,
Associate Professor of Medicine, Hammersmith Hospital; Vermont Regional Diabetes Center,
Harvard Medical School, Clinical Senior Lecturer, Fletcher Allen Health Care,
Boston, Massachusetts Department of Metabolic Medicine, Burlington, Vermont
Division of Investigative Science,
Rexford S. Ahima, MD, PhD, Imperial College, London, Hammersmith Susan Bonner-Weir, PhD,
Attending Endocrinologist, Hospital Campus, Senior Investigator, Section of Islet
Hospital of the University of London, United Kingdom Transplantation and Cell Biology,
Pennsylvania; Joslin Diabetes Center;
Assistant Professor of Medicine, Division of Donald M. Barnett, MD, Associate Professor of Medicine,
Endocrinology, Senior Consultant, Harvard Medical School,
University of Pennsylvania School of Joslin Diabetes Center; Boston, Massachusetts
Medicine, Assistant Clinical Professor of
Philadelphia, Pennsylvania Medicine, Florence M. Brown, MD,
Harvard Medical School, Senior Staff Physician,
Lloyd M. Aiello, MD, Boston, Massachusetts Adult Internal Medicine,
Director, Beetham Eye Institute, Joslin Diabetes Center;
Joslin Diabetes Center; Ananda Basu, MD, MRCP, Instructor in Medicine,
Massachusetts Eye and Ear Infirmary; Consultant, Endocrinology and Harvard Medical School,
Associate Clinical Professor of Metabolism, Mayo Clinic; Boston, Massachusetts
Ophthalmology, Assistant Professor, Department of Internal
Harvard Medical School, Medicine, A. Enrique Caballero, MD,
Boston, Massachusetts Mayo Clinic College of Medicine, Associate Director of Professional Education,
Rochester, Minnesota Director of the Latino Diabetes Initiative,
Lloyd Paul Aiello, MD, PhD, Joslin Diabetes Center;
Associate Director, Beetham Eye Institute, Richard S. Beaser, MD, Instructor in Medicine,
Joslin Diabetes Center; Medical Executive Director of Professional Harvard Medical School,
Massachusetts Eye and Ear Infirmary; Education, Strategic Initiatives, Boston, Massachusetts
Associate Professor of Ophthalmology, Joslin Diabetes Center;
Harvard Medical School, Assistant Clinical Professor of Medicine, Jonathan Castro, MD,
Boston, Massachusetts Harvard Medical School, Clinical Assistant Instructor,
Boston, Massachusetts Division of Endocrinology,
Cameron M. Akbari, MD, State University of New York Downstate,
Attending Vascular Surgeon; Peter H. Bennett, MB, FRCP, Brooklyn, New York
Director, Vascular Diagnostic Laboratory, Scientist Emeritus, Phoenix Epidemiology
Washington Hospital Center, and Clinical Research Branch, Melissa K. Cavaghan, MD,
Washington, DC National Institute of Diabetes and Digestive Assistant Professor of Clinical Medicine,
and Kidney Diseases, Division of Endocrinology and Metabolism,
Stephanie A. Amiel, BSc, MD, FRCP, Phoenix, Arizona Indiana University School of Medicine,
Professor of Diabetic Medicine, Indianapolis, Indiana
King’s College Hospital; Caroline S. Blaum, MD, MS,
R.D. Lawrence Professor of Diabetic Associate Professor of Internal Medicine, Jerry D. Cavallerano, OD, PhD,
Medicine, Division of Geriatic Medicine, Staff Optometrist, Beetham Eye Institute,
Guy’s King’s and St. Thomas’ School of University of Michigan Medical School; Joslin Diabetes Center;
Medicine, Research Scientist, Associate Professor,
King’s College London, Ann Arbor DVAMC GRECC, New England College of Optometry,
London, United Kingdom Ann Arbor, Michigan Boston, Massachusetts
Barbara J. Anderson, PhD, Stephen R. Bloom, MBBChir, MA, MD, Karen Hanson Chalmers, MS, RD, CDE,
Pediatric Psychologist, DSc, FRCP, FRCPath, Advanced Practice Diabetes Specialist,
Department of Pediatric Endocrinology and Clinical Director of Pathology and Therapy Nutrition Services and Insulin Pump
Metabolism, Services, Program,
Texas Children’s Hospital; Endocrinology, Hammersmith Hospitals Joslin Clinic,
Associate Professor, NHS Trust; Joslin Diabetes Center,
Department of Pediatrics, Professor of Medicine, Department of Boston, Massachusetts
Baylor College of Medicine, Metabolic Medicine;
Houston, Texas Head, Division of Investigative Science,
Imperial College, London, Hammersmith
Houman Ashrafian, BM, BChir, MA, MRCP, Hospital Campus,
Specialist Registrar, London, United Kingdom
Ealing Hospital
Middlesex, United Kingdom
viii CONTRIBUTORS
Alice Y.Y. Cheng, MD, FRCPC, George M. Eliopoulos, MD, Ann E. Goebel-Fabbri, PhD,
Endocrinologist, Division of Endocrinology Physician, Department of Medicine, Psychologist,
and Metabolism; Division of Infectious Diseases, Mental Health Unit,
Lecturer, Department of Medicine, Beth Israel Deaconess Medical Center; Joslin Diabetes Center;
University of Toronto, Professor of Medicine, Instructor in Psychiatry,
Toronto, Ontario, Canada Harvard Medical School, Harvard Medical School,
Boston, Massachusetts Boston, Massachusetts
Stuart R. Chipkin, MD,
Professor of Exercise Science, Elof Eriksson, MD, PhD, Allison B. Goldfine, MD,
University of Massachusetts, Chief of Plastic and Reconstructive Surgery, Research Associate, Cellular and
Amherst, Massachusetts Division of Plastic Surgery, MolecularPhysiology and
Brigham and Women’s Hospital, Clinical Research,
Ondine Cleaver, PhD, The Children’s Hospital Boston; Joslin Diabetes Center;
Postdoctoral Fellow, Joseph E. Murray Professor of Plastic and Assistant Professor of Medicine,
Molecular and Cellular Biology, Reconstructive Surgery, Harvard Medical School,
Harvard University, Harvard Medical School, Boston, Massachusetts
Boston, Massachusetts Boston, Massachusetts
Irwin Goldstein, MD,
Sheila Collins, PhD, Edward P. Feener, PhD, Professor of Urology,
Senior Investigator, Investigator, Section on Vascular Cell Biology, Boston University School of Medicine,
Endocrine Biology Program, Joslin Diabetes Center; Boston, Massachusetts
CIIT Centers for Health Research, Assistant Professor of Medicine,
Research Triangle Park, North Carolina Harvard Medical School, Laurie J. Goodyear, PhD,
Boston, Massachusetts Investigator and Section Head: Metabolism,
Patrick Concannon, PhD, Joslin Diabetes Center;
Director, Molecular Genetics Program, Jeffrey S. Flier, MD, Assistant Professor of Medicine,
Benaroya Research Institute; Chief Academic Officer, Harvard Medical School,
Affiliate Professor, Department of Beth Israel Deaconess Medical Center; Boston, Massachusetts
Immunology, George C. Reisman Professor of Medicine,
University of Washington, Harvard Medical School, Raj K. Goyal, MD,
Seattle, Washington Boston, Massachusetts Staff Physician,
Gastroenterology,
Ramachandiran Cooppan, MBChB, Roy Freeman, MD, VABoston Healthcare System;
FRCP(c)FACE, Director, Autonomic and Peripheral Nerve Mallinckrodt Professor of Medicine,
Senior Staff Physician, Department of Laboratory, Department of Neurology, Harvard Medical School,
Medicine, Beth Israel Deaconess Medical Center; Boston, Massachusetts
Beth Israel Deaconess Medical Center; Associate Professor of Neurology,
Assistant Clinical Professor of Medicine, Harvard Medical School, Daryl K. Granner, MD,
Harvard Medical School, Boston, Massachusetts Staff Physician,
Boston, Massachusetts VATennessee Valley Healthcare System;
Parham A. Ganchi, MD, PhD, Director, Vanderbilt Diabetes Center,
Alessandro Doria, MD, PhD, Assistant Professor of Plastic Surgery, Vanderbilt University Medical Center;
Investigator, Section on Genetics and Division of Plastic and Reconstructive Professor of Molecular Physiology and
Epidemiology, Surgery, Biophysics,
Joslin Diabetes Center; University of Medicine and Dentistry of Vanderbilt University,
Assistant Professor of Medicine, New Jersey Hospital, Nashville, Tennessee
Harvard Medical School, Newark, New Jersey
Boston, Massachusetts Gabriella Gruden, MD, PhD,
Om P. Ganda, MD, Researcher, Internal Medicine,
Jeffrey S. Dover, MD, FRCPC, Senior Physician, University of Turin,
Director, SkinCare Physicians of Chestnut Joslin Clinic, Joslin Diabetes Center; Turin, Italy
Hill, Associate Clinical Professor of Medicine,
Chestnut Hill, Massachusetts; Harvard Medical School, Joel F. Habener, MD,
Professor of Dermatology, Boston, Massachusetts Chief, Medicine, Laboratory of Molecular
Dartmouth Medical School, Endocrinology,
Hanover, New Hampshire; Michael S. German, MD, Massachusetts General Hospital;
Professor of Dermatology, Hormone Research Institute and Diabetes Professor of Medicine,
Yale University School of Medicine, Center, Harvard Medical School,
New Haven, Connecticut Department of Medicine, Boston, Massachusetts
University of California at San Francisco,
Victor J. Dzau, MD, San Francisco, California Philippe A. Halban, PhD,
Chancellor for Health Affairs at Duke Professor, Department of Genetic Medicine
University; John M. Giurini, DPM, and Development,
President and CEO of Duke University Chief, Division of Podiatry, University of Geneva,
Health System, Beth Israel Deaconess Medical Center; Geneva, Switzerland
Durham, North Carolina Associate Professor of Surgery,
Harvard Medical School, Jeffrey B. Halter, MD,
George S. Eisenbarth, MD, PhD, Boston, Massachusetts Director, Geriatrics Center and Institute of
Director, Barbara Davis Center for Childhood Gerontology;
Diabetes, Benjamin Glaser, MD, Chief, Division of Geriatric Medicine, and
University of Colorado Health Sciences Director, Endocrinology and Metabolism Professor of Internal Medicine,
Center; Service, University of Michigan Medical School,
Professor of Pediatrics/Immunology/ Department of Internal Medicine, Ann Arbor, Michigan
Medicine, Hadassah-Hebrew University Medical
University of Colorado, Center,
Denver, Colorado Jerusalem, Israel