THE HEART IN DIABETES

Transcription

1 THE HEART IN DIABETES

2 Developments in Cardiovascular Medicine 173. C.A. Nienaber and U.Sechtem (eds.): Imaging and Intervention in Cardiology ISBN G. Assmann (ed.): HDL Deficiency and Atherosclerosis ISBN N.M. van Hemel, F.H.M. Wittkampf and H. Ector (eds.): The Pacemaker Clinic of the 90's. Essentials in Brady-Pacing ISBN N. Wilke (ed.): Advanced Cardiovascular MRI of the Heart and Great Vessels ISBN M.LeWinter. H. Suga and M.W. Watkins (eds.): Cardiac Energetics: From Emax to Pressure-volume Area ISBN R.I. Siegel (ed.): Ultrasound Angioplasty ISBN D.M. Yellon and G.I. Gross (eds.): Myocardial Protection and the Katp Channel. ISBN A.V.G. Bruschke. I.H.C. Reiber. K.I. Lie and H.I.I. Wellens (eds.): Lipid Lowering Therapy and Progression of Coronary Atherosclerosis ISBN A.S.A. Abd-Elfattah and A.S. Wechsler (eds.): Purines and Myocardial Protection ISBN M. Morad, S. Ebashi, W. Trautwein and Y. Kurachi (eds.): Molecular Physiology and Pharmacology of Cardiac Ion Channels and Transporters ISBN A.M. Oto (ed.): Practice and Progress in Cardiac Pacing and Electrophysiology ISBN W.H. Birkenhager (ed.): Practical Management of Hypertension. Second Edition ISBN

3 The Heart in Diabetes edited by John C. Chatham, John R. Forder Department of Radiology, Division of NMR Research Johns Hopkins University School of Medicine, Baltimore MD and John H. McNeill Faculty of Pharmaceutical Sciences University of British Columbia 2146 East Mall, Vancouver, British Columbia, CANADA V6T 1W5

4 Distributors for North America: Kluwer Academic Publishers 101 Philip Drive Assinippi Park Norwell, Massachusetts USA Distributors for all other countries: Kluwer Academic Publishers Group Distribution Centre Post Office Box AH Dordrecht, THE NETHERLANDS Library of Congress Cataloging-in-Publication Data A C.I.P. Catalogue record for this book is available from the Library of Congress. ISBN-13: DOl: / e-isbn-13: by Kluwer Academic Publishers Softcover reprint of the hardcover 1st edition 1996 All rights reserved. No part of this publication may be reproduced, stored in a retrieval system or transmitted in any form or by any means, mechanical, photo-copying, recording, or otherwise, without the prior written permission of the publisher, Kluwer Academic Publishers, 101 Philip Drive, Assinippi Park, Norwell, Massachusetts Printed on acid1ree paper.

5 List of Contributors Louis Arroyo, M.D. The Department of Medicine University of Medicine and Dentistry of New Jersey New Jersey Medical School Newark, NJ John C. Chatham, D.Phii. Department of Radiology Division ofnmr Research Johns Hopkins University School of Medicine Baltimore, MD Vijay"n Elimban, Ph.D. Faculty of Medicine Division of Cardiovascular Sciences st. Boniface General Hospital Research Centre, University of Manitoba Winnipeg, Canada, R2H 2A6 Frederick S. Fein, M.D. Department of Medicine Albert Einstein College of Medicine 100 Morris Park Avenue Bronx, NY David L Geenen, Ph.D. Montefiore Medical Center Cardiology Division 111 East 210th St. Bronx, NY Maren Laughlin, Ph.D. Department of Surgery Ross Hall Eye St The George Washington University Washington DC Alain Borc7-uk, M.D. Department of Pathology Albert Einstein College of Medicine 1300 Morris Park Avenue Bronx, NY Naranjan S. Dhalla,Ph.D.,M.D.(Hon) Faculty of Medicine Division of Cardiovascular Sciences st. Boniface General Hospital Research Centre, University of Manitoba Winnipeg, Canada, R2H 2A6 Stephen M. Factor, M.D. Department of Pathology Albert Einstein College of Medicine, 1300 Morris Park Avenue Bronx, NY John R. Forder, Ph.D. Department of Radiology Division ofnmr Research Johns Hopkins University School of Medicine Baltimore, MD Leonard S. Golfman, Ph.D. Faculty of Medicine Division of Cardiovascular Sciences St. Boniface General Hospital Research Centre, University of Manitoba Winnipeg, Canada, R2H 2A6 Gary D. Lopaschuk, Ph.D. Cardiovascular Disease Research Group, Departments of Pediatrics and Pharmacology The University of Alberta Edmonton, Canada, T6G 2S2

6 Ashwani Malhotra, Ph.D. Montefiore Medical Center Cardiology Division 111 East 210th St. Bronx, NY Timothy J. Regan, M.D. The Department of Medicine University of Medicine and Dentistry of New Jersey New Jersey Medical School Newark, NJ Makilzhan Shanmugam, M.D. The Department of Medicine University of Medicine and Dentistry of New Jersey New Jersey Medical School Newark, NJ Nobuakira Takeda, M.D. Department of Internal Medicine Aoto Hospital, Jikei University Tokyo, Japan John H. McNeill, Ph.D. Faculty of Pharmaceutical Sciences, University of British Columbia 2146 East Mall Vancouver British Columbia Canada, V6T lz3 Brian Rodrigues, Ph.D. Faculty of Pharmaceutical Sciences, University of British Columbia 2146 East Mall Vancouver British Columbia Canada, V6T lz3 Abbas Shehadeh, M.D. The Department of Medicine University of Medicine and Dentistry of New Jersey New Jersey Medical School Newark, NJ 07103

7 Table of Contents 1: Clinical Manifestations of Diabetic Cardiomyopathy Frederick S. Fein.... 2: Pathological Alterations of the Heart in Diabetes Mellitus Alain Borczuk and Stephen M. Factor.... 3: Alterations of Cardiac Function, Composition and Rhythm as a Consequence of Diabetes Makilzhan Shanmugam, Louis Arroyo, Abbas Shehadeh and Timothy J. Regan : Therapeutic Interventions in the Diabetic heart John H. McNeill and Brian Rodrigues : Effect of Diabetes on Protein Synthesis in the Myocardium David Geenen and Ashwani Malhotra : Remodelling of Subcellular Organelles During the Development of Diabetic Cardiomyopathy Naranjan S. Dhalla, Leonard S. Golfman, Vijayan Elimban and Nobuakira Takeda : Ketone Body Metabolism in the Diabetic Heart John R. Forder : Cardiac Glycogen Metabolism in Diabetes Maren Laughlin : The Effect of Diabetes on Myocardial Glucose Metabolism John C. Chatham : Fatty Acid Metabolism in the Heart Following Diabetes Gary D. Lopaschuk : Conclusion John C Chatham, John R. Forder and John H. McNeill Index

8 Preface Diabetes is a major public health problem which is expected to affect 160 million people world wide by the year During the past 70 years the average life expectancy of diabetic patients has significantly increased; however, it is still substantially lower than the general population. Prior to the discovery of insulin the primary causes of death for people with diabetes were diabetic coma, infections and cardiovascular disease. The use of insulin has almost eliminated death from diabetic coma and dramatically decreased death from infections; consequently cardiovascular disease is now the leading cause of death in the diabetic population. Although cardiovascular disease remains the leading cause of death for the general population, diabetic patients have greatly increased risks of heart failure and coronary artery disease compared to nondiabetics. Furthermore, survival rates following acute myocardial infarction are markedly lower than the general population. Until recently the elevated risk of cardiovascular disease was presumed to be a direct consequence of the increased incidence of atherosclerosis in diabetes. Several decades of epidemiological and experimental research has suggested that there is a specific diabetes-induced cardiomyopathy that is independent of other risk factors for heart disease, such atherosclerosis and hypertension. Despite the impact of heart disease in limiting the quality and longevity of life for diabetic patients, there is no consensus as to the pathophysiologic alterations that are involved. Clearly an understanding of the effects of diabetes on the heart is an important step in the development of strategies to reduce the incidence of heart disease for diabetic patients, thus increasing their overall lifeexpectancy and quality of life. In this book we bring together the different lines of evidence supportive of the idea of a diabetic cardiomyopathy. The first chapter provides an overview of the impact of cardiac dysfunction on the mortality and morbidity of the diabetic population in general, as well as a presentation of clinical aspects of heart disease in diabetes. This is followed by chapters concerned with the pathological and functional changes that occur in the heart as a result of diabetes and a description of the various therapeutic

9 interventions that are available to reverse the effects of diabetes on the heart. Subsequent chapters focus on changes in protein synthesis, membrane function and intermediary metabolism that take place following the onset of diabetes. Since these alterations precede many of the functional and pathological changes, it may be that the processes responsible for the functional decline and tissue injury are initiated by diabetes-induced changes at the cellular and/or biochemica1level.