Hypoglycaemia in Clinical Diabetes

Hypoglycaemia in Clinical Diabetes

(Parte 1 de 7)

Hypoglycaemia in Clinical Diabetes Second Edition

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Hypoglycaemia in Clinical Diabetes Second Edition

Edited by

Brian M. Frier The Royal Infirmary of Edinburgh, Scotland, UK

Miles Fisher Glasgow Royal Infirmary, Scotland, UK

Copyright © 2007 John Wiley & Sons Ltd, The Atrium, Southern Gate, Chichester, West Sussex PO19 8SQ, England

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Anniversary Logo Design: Richard J. Pacifico Library of Congress Cataloging in Publication Data

Hypoglycaemia in clinical diabetes/edited by Brian M. Frier and Miles Fisher. — 2nd ed. p. ; cm.

Includes bibliographical references and index. ISBN 978-0-470-01844-6 (cloth:alk. paper) 1. Hypoglycemia. 2. Diabetes—Treatment—Complications. 3. Hypoglycemic agents—Side effects. I. Frier, Brian M. I. Fisher, Miles. II. Title: Hypoglycemia in clinical diabetes. [DNLM: 1. Hypoglycemia—complications. 2. Hypoglycemia—physiopathology. 3. Diabetes Complications. 4. Insulin—adverse effects. WK 880 H9963 2007] RC662.2.H965 2007 616.4′6—dc22 2007012095

British Library Cataloguing in Publication Data A catalogue record for this book is available from the British Library ISBN 978-0-470-01844-6

Typeset in 10/12pt Times by Integra Software Services Pvt. Ltd, Pondicherry, India Printed and bound in Great Britain by Antony Rowe Ltd, Chippenham, Wiltshire This book is printed on acid-free paper responsibly manufactured from sustainable forestry in which at least two trees are planted for each one used for paper production.

To Emily, Ben and Marc


Preface ix Contributors xi

1 Normal Glucose Metabolism and Responses to Hypoglycaemia 1 Ian A. Macdonald and Paromita King

2 Symptoms of Hypoglycaemia and Effects on Mental Performance and Emotions 25 Ian J. Deary

3 Frequency, Causes and Risk Factors for Hypoglycaemia in Type 1

Diabetes 49 Mark W.J. Strachan

4 Nocturnal Hypoglycaemia 83 Simon R. Heller

5 Moderators, Monitoring and Management of Hypoglycaemia 101 Tristan Richardson and David Kerr

6 Counterregulatory Deficiencies in Diabetes 121 David Kerr and Tristan Richardson

7 Impaired Awareness of Hypoglycaemia 141 Brian M. Frier

8 Risks of Strict Glycaemic Control 171 Stephanie A. Amiel

9 Hypoglycaemia in Children with Diabetes 191 Krystyna A. Matyka

10 Hypoglycaemia in Pregnancy 217 Ann E. Gold and Donald W.M. Pearson

1 Hypoglycaemia in Type 2 Diabetes and in Elderly People 239 Nicola N. Zammitt and Brian M. Frier

12 Mortality, Cardiovascular Morbidity and Possible Effects of

Hypoglycaemia on Diabetic Complications 265 Miles Fisher and Simon R. Heller viii CONTENTS

13 Long-term Effects of Hypoglycaemia on Cognitive Function and the

Brain in Diabetes 285 Petros Perros and Ian J. Deary

14 Living with Hypoglycaemia 309 Brian M. Frier

Index 3


In the second edition of this book, we have continued to emphasise the clinical significance of hypoglycaemia to the person who has diabetes, particularly when receiving treatment with insulin. Since the first edition of the book was published in 1999, new therapies have emerged, including new insulin analogues and inhaled insulin, and monitoring systems are now available that can provide continuous recording of blood glucose. However, far from minimising the risk of hypoglycaemia in clinical practice, the newer treatments have been shown to be as liable to cause hypoglycaemia as before, while continuous blood glucose monitoring has revealed that this side-effect of insulin therapy is even more common than was believed previously. The frequency of severe hypoglycaemia in vulnerable groups such as children and elderly people receiving insulin therapy is unacceptably high, and presents potentially serious risks to health as well as diminishing their quality of life. Much scientific research in recent years has focused on the effects of hypoglycaemia on the brain, providing a greater understanding of the protean effects of this metabolic abnormality. New data and concepts have been incorporated in this edition, particularly where these are of importance to clinical practice.

In updating and revising this book about hypoglycaemia, particular emphasis has been given to the risk factors for hypoglycaemia and how these may be reduced or avoided. New chapters have been included to discuss recognised moderators of hypoglycaemia and the role of new glucose monitoring systems, to address the increasing problem of hypoglycaemia in people with type 2 diabetes and the elderly person, and to acknowledge the major importance of nocturnal hypoglycaemia, which is frequently not identified in clinical practice but can have serious consequences, not only in its immediate morbidity, but also in promoting the development of the acquired syndromes of hypoglycaemia.

We are grateful for the expert assistance and support of the colleagues who have contributed chapters, some of whom are new as authors for this edition. All have skillfully highlighted the relevance of the enhancement of scientific knowledge in this field to the everyday management of diabetes, which we hope will assist all members of the diabetes team in their efforts to prevent and manage the extremely common but unwanted scourge that is hypoglycaemia.

Brian M. Frier Miles Fisher


Professor Stephanie A. Amiel, R.D. Lawrence Professor of Diabetes, Department of Medicine, King’s College Hospital, Bessemer Road, London, SE5 9PJ (e-mail: stephanie.amiel@kcl.ac.uk

Professor Ian J. Deary, Department of Psychology, University of Edinburgh, 7 George Square, Edinburgh, EH8 9JZ (e-mail: ian.deary@ed.ac.uk

Dr Miles Fisher, Consultant Physician, Glasgow Royal Infirmary, Glasgow, G4 0SF (e-mail: miles.fisher@northglasgow.scot.nhs.uk

Professor Brian M. Frier, Consultant Physician, Department of Diabetes, Royal Infirmary, 51 Little France Crescent, Edinburgh, EH16 4SA (e-mail: brian.frier@luht.scot.nhs.uk

Dr Ann E. Gold, Consultant Physician, Wards 27 and 28, Aberdeen Royal Infirmary, Foresterhill, Aberdeen, AB25 2ZN (e-mail: ann.gold@nhs.net

Professor Simon R. Heller, Professor of Clinical Diabetes, Clinical Sciences Centre, Department of Diabetes & Endocrinology, Northern General Hospital, Herries Road, Sheffield, S5 7AU (e-mail: s.heller@sheffield.ac.uk

Dr David Kerr, Consultant Physician, The Royal Bournemouth Hospital, Castle Lane East, Bournemouth, BH7 7DW (e-mail: David.Kerr@rbch.nhs.uk

Dr Paromita King, Consultant Physician, Jenny O’Neill Diabetes Centre, Derbyshire Royal Infirmary, London Road, Derby, DE1 2QY (e-mail: Paru.King@derbyhospitals.nhs.uk

Professor Ian A. Macdonald, Professor of Metabolic Physiology, Department of Physiology and Pharmacology, Medical School, Queen’s Medical Centre, Nottingham, NG7 2UH (e-mail: Ian.Macdonald@nottingham.ac.uk

Dr Krystyna A. Matyka, Senior Lecturer in Paediatrics, University of Warwick Medical School, Division of Clinical Sciences, CSB Research Wing, UHCW Trust, Clifford Bridge Road, Coventry, CV2 2DX (e-mail: K.A.Matyka@warwick.ac.uk

Dr Donald W.M. Pearson, Consultant Physician, Aberdeen Royal Infirmary, Foresterhill, Aberdeen, AB25 2ZN (e-mail: Dwm.Pearson@arh.grampian.scot.nhs.uk

Dr Petros Perros, Consultant Endocrinologist, Ward 15, Freeman Hospital, Freeman Road, Newcastle-Upon-Tyne, NE7 7DN (e-mail: Petros.Perros@ncl.ac.uk

Dr Tristan Richardson, Consultant Physician, Bournemouth Diabetes and Endocrine Centre, The Royal Bournemouth Hospital, Castle Lane East, Bournemouth, BH7 7DW (e-mail: Tristan.Richardson@rbch.nhs.uk xii CONTRIBUTORS

Dr Mark W.J. Strachan, Consultant Physician, Metabolic Unit, Western General Hospital, Crewe Road, Edinburgh, EH4 2XU (e-mail: mark.strachan@luht.scot.nhs.uk

Dr Nicola N. Zammitt, Specialist Registrar, Department of Diabetes, Royal Infirmary of Edinburgh, 51 Little France Crescent, Edinburgh, EH16 4SA (e-mail: nicolazammitt@hotmail.com

1 Normal Glucose Metabolism and Responses to Hypoglycaemia

Ian A. Macdonald and Paromita King

Control of blood glucose is a fundamental feature of homeostasis, i.e., the process by which the internal environment of the body is maintained stable allowing optimal function. Blood glucose concentrations are regulated within a narrow range (which in humans is known as normoglycaemia or euglycaemia) despite wide variability in carbohydrate intake and physical activity. Teleologically, the upper limit is defended because high glucose concentrations cause microvascular complications, and the lower limit, because the brain cannot function without an adequate supply of glucose. In this chapter the mechanisms that protect against hypoglycaemia in healthy individuals and the physiological consequences of low glucose concentrations are discussed.

Humans evolved as hunter-gatherers and, unlike people today, did not consume regular meals. Mechanisms therefore evolved for the body to store food when it was in abundance, and to use these stores to provide an adequate supply of energy, in particular in the form of glucose when food was scarce. Cahill (1971) originally described the ‘rules of the metabolic game’ which humans had to follow to ensure their survival. These rules were modified by Tattersall (personal communication) and are as follows:

1. Maintain glucose within very narrow limits.

2. Maintain an emergency energy source (glycogen) which can be tapped quickly for fleeing or fighting.

3. Waste not want not, i.e., store (fat and protein) in times of plenty. 4. Use every trick in the book to maintain protein reserves.

Hypoglycaemia in Clinical Diabetes, 2nd Edition. Edited by B.M. Frier and M. Fisher © 2007 John Wiley & Sons, Ltd

(Parte 1 de 7)