Diabetes Mellitus in Women Adolescence Through Pregnancy and Menopause      3rd  Edition 2004 Lippincott Williams & Wilkins Philadelphia 530 Walnut Street, Philadelphia, PA 19106 USA 978-0-7817-3861-3 0-7817-3861-X Acquisitions Editor: Ruth Weinberg Developmental Editor: Grace Caputo, Erin McMullan Production Manager: Toni Ann Scaramuzzo Production Editor: Michael Mallard Manufacturing Manager: Benjamin Rivera Cover Designer: Brian Crede Compositor: Lippincott Williams & Wilkins Desktop Division Printer: Maple Press © 2004 by LIPPINCOTT WILLIAMS & WILKINS 530 Walnut Street Philadelphia, PA 19106 USA LWW.com All rights reserved. This book is protected by copyright. No part of this book may be reproduced in any form or by any means, including photocopying, or utilized by any information storage and retrieval system without written permission from the copyright owner, except for brief quotations embodied in critical articles and reviews. Materials appearing in this book prepared by individuals as part of their official duties as U.S. government employees are not covered by the above-mentioned copyright. Printed in the USA Library of Congress Cataloging-in-Publication Data ISBN: 0-7817-3861-X Care has been taken to confirm the accuracy of the information presented and to describe generally accepted practices. However, the authors, editors, 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, expressed or implied, with respect to the currency, completeness, or accuracy of the contents of the publication. Application of this information in a particular situation remains the professional responsibility of the practitioner. The authors, editors, 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 FDA status of each drug or device planned for use in their clinical practice. 10 9 8 7 6 5 4 3 2 1 AUTHORS E. Albert Reece M.D., PH.D., M.B.A. Vice Chancellor and Dean Professor of Obstetrics & Gynecology, Internal Medicine and Biochemistry University of Arkansas College of Medicine Little Rock, Arkansas Donald R. Coustan M.D. Chace/Joukowsky Professor and Chair Department of Obstetrics and Gynecology Brown Medical School Obstetrician and Gynecologist in Chief Women and Infants Hospital of Rhode Island Providence, Rhode Island Steven G. Gabbe M.D. Dean, Vanderbilt University School of Medicine Professor of Obstetrics and Gynecology Vanderbilt University Medical Center Nashville, Tennessee CONTRIBUTORS Frederick C. Battaglia M.D. Professor of Pediatrics, Department of Pediatrics, University of Colorado Health Sciences Center, Aurora, Colorado Peter H. Bennett M.D., F.R.C.P. Senior Investigator, Phoenix Epidemiology and Clinical Research Branch, NIDDK, NIH, Phoenix, Arizona Wendy J. Brickman M.D. Assistant Professor of Pediatrics, Northwestern University Feinberg School of Medicine, Children's Memorial Hospital, Chicago, Illinois Thomas A. Buchanan M.D. Departments of Obstetrics and Gynecology and Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California Marshall W. Carpenter M.D. Brown University, Women and Infants Hospital of Rhode Island, Providence, Rhode Island Patrick Catalano M.D. Professor of Reproductive Biology, Case Western Reserve University; Chairman, Department of Obstetrics and Gynecology, Metro-Health Medical Center, Cleveland, Ohio Nam H. Cho M.D., Ph.D., C.C.D. Professor of Preventive Medicine, Ajou University School of Medicine; Director of Clinical Epidemiology, Ajou University Hospital, Suwon, Korea Larry Cousins M.D. Division of Perinatology, Mary Birch Hospital for Women, San Diego, California Donald R. Coustan M.D. Chace/Joukowsky Professor and Chair, Department of Obstetrics and Gynecology, Brown Medical School; Obstetrician and Gynecologist in Chief, Women and Infants Hospital of Rhode Island, Providence, Rhode Island Dana Dabelea M.D., Ph.D. Assistant Professor, Preventive Medicine and Biometrics, University of Colorado Health Sciences Center, Denver, Colorado Gernot Desoye Ph.D. Clinic of Obstetrics and Gynecology, Karl-Franzens-University, Vienna, Austria Esther Eisenberg M.D., M.P.H. Department of Obstetrics and Gynecology, Vanderbilt University Medical Center, Nashville, Tennessee Steven C. Elbein M.D. Department of Endocrinology, John L. McClellan Veterans Hospital, Little Rock, Arkansas Ulf J. Eriksson M.D. Professor, Department of Medical Cell Biology, University of Uppsala, Uppsala, Sweden Steven G. Gabbe M.D. Dean, School of Medicine, Department of Obstetrics and Gynecology, Vanderbilt University, Nashville, Tennessee Sandro Gabrielli M.D. Cattefra Frisiopatologia Prenatale, Clinica Obstetrica e Ginecologia, Universita de Bologna, Bologna, Italy Henry L. Galan M.D. Assistant Professor, Department of Obstetrics and Gynecology, Division of Perinatal Medicine, University of Colorado Health Sciences Center, Aurora, Colorado Philip A. Goldberg M.D. Department of Internal Medicine, Section of Endocrinology, Yale University School of Medicine, New Haven, Connecticut Andrea C. Hinton M.D. Maternal Fetal Medicine Fellow, Department of Obstetrics and Gynecology, University of Cincinnati School of Medicine, Cincinnati, Ohio Irl B. Hirsch M.D. Department of Medicine, Division of Metabolism, Endocrinology, and Nutrition, University of Washington School of Medicine; Diabetes Care Center, University of Washington Medical Center, Seattle, Washington Carol J. Homko Ph.D., R.N. Temple University Hospital, Philadelphia, Pennsylvania Lois Jovanovic M.D. Director and Chief Scientific Officer Sansum Medical Research Institute; Clinical Professor of Medicine, University of Southern California, Los Angeles, California; Adjunct Professor of Biomolecular Science and Engineering, University of California-Santa Barbara, Santa Barbara, California John L. Kitzmiller M.D. Los Gatos, California Siri L. Kjos M.D. Professor, Department of Obstetrics and Gynecology, Keck School of Medicine, University of Southern California, Los Angeles, California Mark B. Landon M.D. Professor and Vice Chairman, Department of Obstetrics and Gynecology, Ohio State University School of Medicine, Columbus, Ohio Oded Langer M.D. Babcock Professor and Chairman, Department of Obstetrics and Gynecology, St. Lukes-Roosevelt Hospital Center, University Hospital of Columbia University, New York, New York Gustavo F. Leguizamón M.D. Assistant Professor, Department of Obstetrics and Gynecology, CEMIC University, Chief High Risk Pregnancy Unit, CEMIC University Hospital, Buenos Aires, Argentina Ginny Lewis M.N., A.R.N.P., C.D.E. Diabetes Care Center, University of Washington Medical Center, Seattle, Washington Barbara Luke Sc.D., M.P.H., R.D. Department of Epidemiology and Public Health, University of Miami School of Medicine, Miami, Florida Jorge H. Mestman M.D. Professor of Medicine and Obstetrics and Gynecology, Keck School of Medicine, University of Southern California, Los Angeles, California Boyd E. Metzger M.D. Tom D. Spies Professor of Medicine, Division of Endocrinology, Northwestern University Feinberg School of Medicine; Attending Physician, Northwestern Memorial Hospital, Chicago, Illinois Menachem Miodovnik M.D. Professor and Chair, Department of Obstetrics and Gynecology, Washington Hospital Center, Washington, D.C. Martin N. Montoro M.D. Division of Maternal-Fetal Medicine, Women's and Children's Hospital, Los Angeles, California Leslie Myatt Ph.D. Department of Obstetrics and Gynecology, University of Cincinnati College of Medicine, Cincinnati, Ohio William Oh M.D. Professor of Pediatrics, Brown University, Rhode Island Hospital, Providence, Rhode Island David J. Pettitt M.D. Senior Scientist, Clinical Research Department, Sansum Medical Research Institute, Santa Barbara, California Gianluigi Pilu M.D. Attending Physician, Department of Obstetrics and Gynecology, University of Bologna School of Medicine, Bologne, Italy Neda Rasouli M.D. Instructor, Division of Endocrinology, University of Arkansas for Medical Sciences, Little Rock VA Hospital, Little Rock, Arkansas E. Albert Reece M.D., Ph.D. Vice Chancellor and Dean, Professor of Obstetrics & Gynecology, Internal Medicine and Biochemistry, University of Arkansas College of Medicine, Little Rock, Arkansas Barak M. Rosenn M.D. Associate Professor of Obstetrics and Gynecology, Columbia University College of Physicians and Surgeons; Director of Obstetrics and Maternal-Fetal Medicine, St. Luke's Roosevelt Hospital Center, New York, New York Robert S. Sherwin M.D. Department of Internal Medicine, Section of Endocrinology, Yale University School of Medicine, New Haven, Connecticut Gerald I. Shulman M.D. Department of Internal Medicine, Section of Endocrinology, Yale University School of Medicine, New Haven, Connecticut Baha M. Sibai M.D. Professor and Chairman, Department of Obstetrics/Gynecology, University of Cincinnati, Cincinnati, Ohio Kathryn M. Thrailkill M.D. Associate Professor of Pediatrics, University of Arkansas College of Medicine, Little Rock, Arkansas A Tribute to Dr. Priscilla White (March 17, 1900 to December 16, 1989) Dr. White in 1987. The past half-century has seen dramatic changes in the management of pregnancy complicated by diabetes, and equally dramatic improvements in outcomes. We of a younger generation of researchers have come late upon the scene, at a time when many of the major advances of the past are taken for granted. For this reason, we feel it appropriate to credit the formative work of early investigators, particularly Dr. Priscilla White, who is acknowledged to be one of the outstanding contributors to the study of diabetes in pregnancy. In the course of working on the first edition of this book, we were privileged to confer with Dr. White and to hear her personal recollections of 50 years of research and patient care, in which Dr. White captured quite vividly the sadness and gloom, and the dismal reproductive prognosis for diabetic women. As Dr. White remembered: Diabetic women were discouraged from becoming pregnant, and termination of pregnancy was often recommended for those who did. Before insulin was available, patients often died during the course of their pregnancy, or their fetuses often died before birth, or as infants Any successful pregnancy was remarkable, so doctors spent almost the entire pregnancy with their patients. We saw them weekly, practically. When they came in labor, I was notified immediately and stayed with them through the entire labor. Delivery was often done prematurely, because if patients were allowed to go to term, the babies would die. We did see, however, fewer mothers die following the introduction of insulin. Dr. White spent virtually all her distinguished career in Boston, primarily at the Joslin Clinic caring for pregnant women with diabetes. Her writings have been extensive and have served as mileposts chronically the advances in management and outcome from the early 1920s through the late 1970s. Her system of classification of diabetes among pregnant women was the international standard by which such patients were described. Her descriptions of the hardships experienced by diabetic individuals prior to the discovery of insulin underscore the tremendous contribution made by Dr. White and her contemporaries. Dr. White will always be respected and remembered with affection by diabetologists, obstetricians, and others who care for diabetic women during their pregnancies. Without the immense strides made by these forerunners, today's advancements might still be out of reach. We presented a copy of the first edition of this book to Dr. White. She graciously accepted our tribute. In 1989, Dr. White died at the age of 89. Fortunately, her contribution lives on! E. Albert Reece M.D., Ph.D., M.B.A. Donald R. Coustan M.D. Steven G. Gabbe M.D. PREFACE The third edition of Diabetes in Women provides an updated educational and therapeutic resource for those who care for women with diabetes during adolescence, pregnancy and beyond. While continuing to provide information about diabetes in pregnancy for the healthcare professional, we have widened our scope in this new edition. The risk factors for diabetes are growing in epidemic proportions, and, as a result, it has become more and more common in the United States. We are witnessing an alarming increase of diabetes in the adolescent. Diabetes is now characterized as a major women's health issue and we recognize that diabetes poses particular challenges for women. As healthcare makes remarkable strides in the control of diabetes, we also recognize that the increase of a woman's life expectancy with the disease presents new challenges. Accordingly, we have expanded this third edition to include the full-spectrum of diabetes in women. The prognosis for women with diabetes continues to improve as does that of their offspring. The revised and current state of knowledge in this edition continues to stress the importance of closely monitored metabolic control in the management of diabetes in pregnancy, but also addresses the entire life cycle of diabetes in adolescence, pregnancy and menopause. The changes recommended by our contributors for the diagnosis of diabetes should prove beneficial to patients, and the value of continued research, innovation and monitoring will constantly change the diabetes landscape. The enormous increase in both our understanding and knowledge has proved beneficial in fostering new management strategies for women of all ages with diabetes. Technology, monitoring, quality of care, and up-to- date guidance and information expand the scope of this edition. The data included have served as the bases for the many new medical considerations and guidelines for managing diabetes throughout a woman's life. This third edition recognizes the educational programs, risk assessments and support for quality care and self-management that should assist in increasing the lifespan of women with diabetes. In aggregate, we have seen overall health improvement for women with diabetes, largely due to better risk assessment, screening, monitoring and management. This edition presents new and updated information on the best treatment options and on dietary management, patient education, genetics, perinatal counseling, diabetes prevention, long-term care of complications, postpartum and menopause. Appropriate care and disease management must be promoted across the span of a woman's life stages. It is our hope that in the ever-changing landscape of information and research, this edition continues to contribute to meet the expanding needs of healthcare professionals. Gratefully, we acknowledge the contributions of many outstanding experts whose efforts and authoritative reviews and guidance make this publication one which reflects new strategies and practices that will bring new advances in understanding and preventing diabetes. E. Albert Reece M.D., Ph.D., M.B.A. Donald R. Coustan M.D. Steven G. Gabbe M.D. P.xi ACKNOWLEDGMENTS We would like to express our gratitude to our contributors, who have painstakingly written comprehensive, highly informative, and scholarly chapters. Efforts like these can only be described as labors of love. In addition, all our secretaries and administrative assistants collectively deserve much praise and commendation for the many hours devoted to typing, reviewing, correcting, copying and mailing the many versions of the manuscripts. Finally, we remain indebted to the editors of Lippincott Williams & Wilkins, especially Ms. Lisa McAllister and Ms. Grace Caputo. Overall, their persistent demeanor enabled the timely publication of this book. We are deeply grateful to all those who collaborated in bringing this project to fruition, from the first edition through the current one. E. Albert Reece M.D., Ph.D., M.B.A. Donald R. Coustan M.D. Steven G. Gabbe M.D. Contents PREFACE ACKNOWLEDGMENTS A Tribute to Dr. Priscilla White Contents Section I. General Medical and Primary Care for Women with Diabetes 1 The History of Diabetes Mellitus 2 The Rising Tide of Diabetes Mellitus: Implications for Women of All Ages 3 Management of Diabetes Mellitus 4 Diabetes Care for Adolescents 5 Genetics, Perinatal Counseling, and Diabetes Education 6 Preconceptional Care of Women with Diabetes 7 Long-Term Care of Medical Complications of Diabetes 8 Menopause and Diabetes Section II. Metabolic Considerations 9 Carbohydrate, Lipid, and Amino Acid Metabolism 10 Metabolic Changes During Normal and Diabetic Pregnancies 11 The Placenta 12 The Biology of Normal and Abnormal Fetal Growth and Development Section III. The Fetus and Placenta 13 Congenital Malformations: Epidemiology, Pathogenesis, and Experimental Methods of Induction and Prevention 14 Perinatal Mortality and Morbidity Section IV. Pregnancy Complicated by Gestational Diabetes 15 Testing for Gestational Diabetes 16 Management of Gestational Diabetes 17 Interaction Between Pregnancy, Gestational Diabetes, and Long-Term Maternal Outcome Section V. Pregnancy Complicated by Pre-Existing Diabetes 18 Glucose Evaluation and Control 19 Insulin Treatment of the Pregnant Patient with Diabetes Mellitus 20 Dietary Management 21 Exercise in Normal and Diabetic Pregnancies 22 Prenatal Diagnosis and Management of Congenital Malformations in Pregnancies Complicated by Diabetes 23 Diagnosis and Management of Abnormal Fetal Growth 24 Fetal Biophysical and Biochemical Testing 25 Diabetic Ketoacidosis in Pregnancy 26 Obstetric Complications in Diabetic Pregnancies 27 Hypertensive Disorders in Pregnancy 28 Diabetic Retinopathy 29 Clinical Diabetic Nephropathy Before and During Pregnancy* 30 Diabetic Neuropathy and Coronary Heart Disease Section VI. Peripartum and Neonatal Care 31 Delivery: Timing, Mode, and Management 32 Postpartum Management, Lactation, and Contraception 33 Neonatal Outcome and Care 34 Long-Term Outcome of Infants of Diabetic Mothers Appendix SUBJECT INDEX