Hypoglycaemia in Clinical Diabetes E-Book

• Herausgeber: John Wiley & Sons
• Kategorie: Fachliteratur
• Sprache: Englisch

Seitenzahl: 875

Veröffentlichungsjahr: 2013

Beschreibung

Hypoglycaemia in Clinical Diabetes

Hypoglycaemia in Clinical Diabetes

Third Edition

If you regularly see patients with diabetes who experience hypoglycaemia and need expert guidance, then this is the book for you.

Hypoglycaemia in Clinical Diabetes, Third Edition once again provides health professionals involved in the management of people with diabetes with an expertly written, comprehensive guide to hypoglycaemia, the most common and feared side effect of insulin treatment for diabetes.

With reference to ADA and EASD guidelines throughout, topics covered include the physiology of hypoglycaemia and the body’s response to low blood glucose, its presentation and clinical features, potential morbidity and optimal clinical management in order to achieve and maintain good glycaemic control.

Particular attention is paid to the way hypoglycaemia is managed in different groups of patients, such as the elderly, in children, or during pregnancy.

New chapters in this edition include:

• Psychological effects of hypoglycaemia
• Technology for hypoglycaemia: CSII and CGM
• Exercise management and hypoglycaemia in type 1 diabetes
• Neurological sequelae of hypoglycaemia

Valuable for diabetologists, endocrinologists, non-specialist physicians and general practitioners, Hypoglycaemia in Clinical Diabetes, Third Edition provides expert clinical guidance to this extremely common and potentially serious complication associated with diabetic management.

Titles of related interst

Diabetes: Chronic Complications, 3rd edition Shaw, ISBN 9780470656181

Diabetes Emergencies: Diagnosis and Clinical Management Katsilambros, ISBN 9780470655917

Leseprobe

Table of Contents

Title page

Copyright page

List of Contributors

Preface

1: Normal Glucose Metabolism and Responses to Hypoglycaemia

Normal Glucose Homeostasis

Effects of Glucose Deprivation on Central Nervous System Metabolism

Counterregulation During Hypoglycaemia

Hormonal Changes During Hypoglycaemia

Physiological Responses

Conclusions

Acknowledgement

2: Symptoms of Hypoglycaemia and Effects on Mental Performance and Emotions

Introduction

Symptoms of Hypoglycaemia

Acute Hypoglycaemia and Cognitive Functioning

Acute Hypoglycaemia and Emotions

Conclusions

3: Counterregulatory Deficiencies in Diabetes

Introduction

Normal Glucose Counterregulation

Age and Glucose Counterregulation

Defective Hormonal Glucose Counterregulation

Mechanisms of Counterregulatory Failure

Conclusions

4: Frequency, Causes and Risk Factors for Hypoglycaemia in Type 1 Diabetes

Introduction

Definitions of Hypoglycaemia

Frequency of Hypoglycaemia

Causes of Hypoglycaemia

Risk Factors for Severe Hypoglycaemia

Conclusions

5: Nocturnal Hypoglycaemia

Introduction

Epidemiology – How Common is Nocturnal Hypoglycaemia?

Causes of Nocturnal Hypoglycaemia

Consequences of Nocturnal Hypoglycaemia

Can Nocturnal Hypoglycaemia be Predicted?

The Somogyi Phenomenon: The Myth of Rebound Hyperglycaemia

Clinical Solutions

Conclusions

6: Impaired Awareness of Hypoglycaemia

Introduction

Normal Responses to Hypoglycaemia

Impaired Awareness of Hypoglycaemia (IAH)

Prevalence of Impaired Awareness of Hypoglycaemia

Pathogenesis of Impaired Awareness of Hypoglycaemia

Impaired Awareness of Hypoglycaemia and Long-Term Effect on Cognitive Function

Human Insulin

Treatment Strategies

Conclusions

7: Risks of Intensive Therapy

Introduction

The Need for Intensive Therapy

Risks of Intensive Insulin Therapy

Hypoglycaemia in Intensive Insulin Therapy

Definition of Hypoglycaemia

Contributors to Increased Risk of Severe Hypoglycaemia in Patients Undertaking Intensified Insulin Therapy

Other Risks of Intensified Insulin Therapy

Patients Unsuitable for Strict Control

Conclusions

8: Management of Acute and Recurrent Hypoglycaemia

Introduction

Moderators of Hypoglycaemia Risk

Monitoring for Hypoglycaemia

Management of Hypoglycaemia

Future Potential Therapeutic Approaches

Conclusions

9: Technology for Hypoglycaemia: CSII and CGM

Introduction

Insulin Pump Therapy

Monitoring

Cost and Reimbursement

Future Expectations

Conclusions

10: Hypoglycaemia in Children with Diabetes

Introduction

Definition of Hypoglycaemia in Childhood

Prevalence of Hypoglycaemia

Signs and Symptoms of Hypoglycaemia

Risk Factors for Hypoglycaemia

Counterregulation in Childhood

Consequences of Hypoglycaemia

Management of Hypoglycaemia

Conclusions

11: Hypoglycaemia During Pregnancy in Women with Pregestational Diabetes

Introduction

Frequency of Hypoglycaemia During Pregnancy

Hormonal Counterregulation

Beta Cell Function

Risk Factors for Severe Hypoglycaemia During Pregnancy

Maternal Consequences of Severe Hypoglycaemia

Hypoglycaemia and Pregnancy Outcome

Hypoglycaemia During Breastfeeding

Prevention and Clinical Management

Treatment

12: Hypoglycaemia in Type 2 Diabetes and in Elderly People

Introduction

Pathophysiology of Hypoglycaemia

Frequency of Hypoglycaemia in Type 2 Diabetes

Morbidity of Hypoglycaemia and Need for Emergency Treatment

Conclusions

13: Mortality, Cardiovascular Morbidity and Possible Effects of Hypoglycaemia on Diabetic Complications

Introduction

Deaths Directly Attributed to Hypoglycaemia

Hypoglycaemia and Sudden Death in Type 1 Diabetes

Dead-in-Bed Syndrome

Risk Factors for Dead-in-Bed Syndrome

Mechanisms of Sudden Death

Hypoglycaemia as a Risk Factor for Increased All Cause and Cardiovascular Mortality

Potential Mechanisms by Which Hypoglycaemia Can Increase Vascular Risk

Hypoglycaemia and Microvascular Complications

Hypoglycaemia and Macrovascular Complications

Conclusions

14: Long-Term Effects of Hypoglycaemia on Cognitive Function in Diabetes

Introduction

Adults with Type 1 Diabetes

Children and Adolescents with Type 1 Diabetes

Animal Models of Recurrent Hypoglycaemia

Recurrent Hypoglycaemia in Older Adults with Type 2 Diabetes

Conclusions

15: Neurological Sequelae of Hypoglycaemia

Introduction

Functional Effects of Hypoglycaemia

Functional and Structural Changes in the Central Nervous System

Structural and Functional Changes in the Central Nervous System

Conclusion

16: Psychological Effects of Hypoglycaemia

Introduction

Experience of Hypoglycaemia

Specific Worries about Hypoglycaemia

Risk Factors for Fear of Hypoglycaemia

Psychological Assessment and Management

Summary

17: Exercise Management and Hypoglycaemia in Type 1 Diabetes

Introduction

Effect of Exercise on Glycaemic Control

Strategies to Maintain Euglycaemia During and After Exercise

Conclusions

18: Living with Hypoglycaemia

Introduction

Psycho-Social Effects

Exercise

Driving

Travel

Employment

Prison and Police Custody

Conclusions

Index

This edition first published 2014 © 2014 by John Wiley & Sons, Ltd.

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Library of Congress Cataloging-in-Publication Data

Hypoglycaemia in clinical diabetes / edited by Brian M. Frier, Simon R. Heller, Rory J. McCrimmon. – Third edition.

p. ; cm.

Includes bibliographical references and index.

ISBN 978-0-470-67200-6 (cloth : alk. paper) – ISBN 978-1-118-69543-2 (ebook) – ISBN 978-1-118-69590-6 (epdf) – ISBN 978-1-118-69787-0 (epub) – ISBN 978-1-118-69790-0

I. Frier, Brian M., editor of compilation. II. Heller, Simon, editor of compilation. III. McCrimmon, Rory J., editor of compilation.

[DNLM: 1. Hypoglycemia–complications. 2. Hypoglycemia–physiopathology. 3. Diabetes Complications. 4. Insulin–adverse effects. WK 880]

RC662.2

616.4'66–dc23

2013024992

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

Wiley also publishes its books in a variety of electronic formats. Some content that appears in print may not be available in electronic books.

Cover images: Top left image: iStock File #19373251 © Willie B. Thomas. Top right image: iStock File #19332350 © Willie B. Thomas. Bottom right image: iStock File #13348540 © MorePixels.

Cover design by Steve Thompson

List of Contributors

Stephanie A. Amiel, MD, FRCP

RD Lawrence Professor of Diabetic Medicine

King's College London

London, UK

Marit R. Bjørgaas, MD, PhD

Adjunct Associate Professor and Senior Consultant

St. Olavs Hospital

Trondheim University Hospital

Trondheim, Norway

Elaine Chow, MSc, MBChB, MRCP(UK)

Clinical Research Fellow and Honorary Diabetes Registrar

University of Sheffield

Sheffield, UK

Peter Damm, MD, DMSc

Professor

Center for Pregnant Women with Diabetes

Department of Obstetrics

Rigshospitalet

University of Copenhagen

Copenhagen, Denmark

Ian J. Deary, PhD, FRCP(Edin), FRCPsych, FMedSci

Professor of Differential Psychology and Director of the Centre for

Cognitive Ageing and Cognitive Epidemiology

University of Edinburgh

Edinburgh, UK

J. Hans DeVries, MD, PhD

Consultant Physician and Endocrinologist

Principal Investigator

Department of Endocrinology

Academic Medical Center

Amsterdam, The Netherlands

Miles Fisher, MD, FRCP(Edin), FRCP(Glas)

Professor

Consultant Physician

Glasgow Royal Infirmary;

Honorary Professor

University of Glasgow

Glasgow, UK

Brian M Frier, MD, FRCP(Edin), FRCP(Glas)

Honorary Professor of Diabetes

British Heart Foundation Centre for Cardiovascular Science

The Queen's Medical Research Institute

University of Edinburgh;

Formerly, Consultant Diabetologist

Royal Infirmary of Edinburgh

Edinburgh, UK

Ian W. Gallen, MD, FRCP, FRCP(Edin)

Consultant Physician and Endocrinologist

Diabetes Centre

Royal Berkshire NHS Trust

Reading, UK

Tibor R.S. Hajos, PhD

Researcher

Department of Medical Psychology

Diabetes Psychology Research Group

VU University Medical Centre

Amsterdam, The Netherlands

Simon R. Heller, DM, FRCP

Professor of Clinical Diabetes and Hon Consultant Physician

Director of Research and Development

Sheffield Teaching Hospitals Foundation Trust;

Department of Human Metabolism

University of Sheffield

Sheffield, UK

Paromita King, DM, FRCP, FRCP(Edin)

Consultant Physician

Derby Hospitals NHS Foundation Trust

Derby, UK

Alistair Lumb, PhD, MRCP(UK)

Specialist Registrar in Diabetes/Endocrinology

Buckinghamshire Healthcare Trust

Buckinghamshire, UK

Ian A. Macdonald, PhD, FSB, FAfN

Professor of Metabolic Physiology

University of Nottingham Medical School

Nottingham, UK

Elisabeth R. Mathiesen, MD, DMSc

Professor

Center for Pregnant Women with Diabetes

Department of Endocrinology

Rigshospitalet

University of Copenhagen

Copenhagen, Denmark

Krystyna A. Matyka, MD, MRCPCH

Associate Clinical Professor

Division of Metabolic and Vascular Health

Warwick University

Coventry, UK

Rory J. McCrimmon MD, FRCP(Edin)

Professor of Experimental Diabetes and Metabolism

Cardiovascular and Diabetes Medicine

Medical Research Institute

University of Dundee

Dundee, UK

Petros Perros, MD, FRCP

Consultant Physician

Department of Endocrinology

Royal Victoria Infirmary

Newcastle upon Tyne, UK

Lene Ringholm, MD, PhD

Specialist Registrar

Center for Pregnant Women with Diabetes

Department of Endocrinology

Rigshospitalet

University of Copenhagen

Denmark

Stefanie M.P.A. Rondags, MSc

Junior Researcher

Department of Medical Psychology

Diabetes Psychology Research Group

VU University Medical Centre

Amsterdam, The Netherlands

Christopher M. Ryan, PhD

Professor

Department of Psychiatry

University of Pittsburgh School of Medicine

Pittsburgh, PA, USA

Josefine E. Schopman, MD, PhD

Department of Internal Medicine

Academic Medical Center

Amsterdam, The Netherlands

Frank J. Snoek, PhD

Professor

Department of Medical Psychology

Diabetes Psychology Research Group

VU University Medical Centre

Amsterdam, The Netherlands

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

Honorary Professor

Consultant in Diabetes and Endocrinology

Metabolic Unit

Western General Hospital;

University of Edinburgh

Edinburgh, UK

Nicola N. Zammitt, MD, FRCP(Edin)

Consultant Physician and

Honorary Clinical Senior Lecturer

Royal Infirmary of Edinburgh

Edinburgh, UK

Preface

Every field in medicine evolves continuously with the incremental acquisition of scientific knowledge leading to developments in clinical management, and hypoglycaemia is no exception. Since the second edition of this book was published in 2007, the interest of clinicians in hypoglycaemia has escalated. This has been stimulated in part by the unexpected and disconcerting results of the ACCORD trial that was conducted in people with type 2 diabetes and the association between severe hypoglycaemia and mortality was confirmed in the ADVANCE and VADT studies. These highlighted the potential hazards associated with strict glycaemic control particularly when other co-morbidities such as coronary heart disease are present, and have focused attention on the need for individualisation of glycaemic targets, especially in vulnerable groups such as the frail and elderly. Most clinicians already recognise that hypoglycaemia is potentially dangerous and even life-threatening, but few appreciated until recently that this side-effect of treatment is actually very common even in type 2 diabetes, and can provoke substantial morbidity (and possibly sudden death), in high risk groups such as those at the extremes of age and in specific situations such as during pregnancy or when undertaking physical exercise. These recent events highlight the importance of physicians and allied health professionals having an in-depth knowledge of hypoglycemia, because an increased understanding of the causes and consequences of hypoglycemia are essential to improving the care of people with diabetes and in helping to shape therapeutic strategies and policies.

The rapid expansion in scientific knowledge about the effects of hypoglycaemia in humans, with research developments on, for example, how hypoglycaemia affects the brain, has direct relevance to people with diabetes, particularly those receiving treatments that increase the risk of hypoglycaemia. As in previous editions of this book, the emphasis has been maintained on the clinical importance of hypoglycaemia and its effects to the individual patient in different age-groups and situations, and the topics that are reviewed should be of direct value to all health care professionals who are involved with the management of people with diabetes. In addition to a change in the team of co-editors for this edition, new authors have been enlisted to provide their expertise and detailed knowledge of different aspects of hypoglycaemia that are highly relevant to everyday practice. Chapters have been added on exercise, psychological effects and the longterm risk of hypoglycaemia to cognitive function, while the role and application of new technologies that may help to identify and avoid hypoglycaemia are reviewed and updated.

We remain indebted to all of the authors for their continuing help, expertise and support to update the content of the book in what is a rapidly changing field. We hope that the clinical information and advice about managing and avoiding hypoglycaemia that is contained in the third edition of this book will assist clinicians with the overall management of diabetes, and particularly increase their awareness, not only of the risks associated with hypoglycaemia, but also how this serious problem affects patients and their families.

Brian M. Frier

Simon R. Heller

Rory J. McCrimmon

1

Normal Glucose Metabolism and Responses to Hypoglycaemia

Ian A. Macdonald1 and Paromita King2

1 University of Nottingham Medical School, Nottingham, UK

2 Derby Hospitals NHS Foundation Trust, Derby, UK

Normal Glucose Homeostasis

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 man had to follow to ensure his survival. These were modified by Tattersall (personal communication) and are:

1. Maintain glucose within very narrow limits.

2. Maintain an emergency energy source (glycogen) that can be tapped quickly in time of need; ‘Fight or Flight’ response.

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.

Insulin and glucagon are the two key hormones controlling glucose homeostasis, and are therefore critical to the mechanisms enabling these ‘rules’ to be followed. The most important processes governed by these hormones are:

Glycogen synthesis and breakdown (glycogenolysis):Glycogen, a carbohydrate, is the most readily accessible energy store and is mostly found in liver and skeletal muscle. Liver glycogen is broken down to provide glucose for all tissues, whereas the breakdown of muscle glycogen results in lactate formation.Gluconeogenesis: This is the production of glucose in the liver from precursors: glycerol, lactate and amino acids (in particular alanine). The process can also occur in the kidneys, but this site is not important under most physiological conditions.Glucose uptake and metabolism (glycolysis) by skeletal muscle and adipose tissue.

The actions of insulin and glucagon are summarised in Boxes 1.1 and 1.2, respectively. Insulin is an anabolic hormone, reducing glucose output by the liver (hepatic glucose output), increasing uptake of glucose by muscle and adipose tissue (increasing peripheral uptake) and increasing protein and fat formation. Glucagon opposes the actions of insulin in the liver. Thus insulin tends to reduce, and glucagon increase blood glucose concentrations.

Box 1.1 Actions of insulin

Liver↑glycogen synthesis (↑ glycogen synthetase activity)↑glycolysis↑lipid formation↑protein formation↓glycogenolysis (↓ phosphorylase activity)↓gluconeogenesis↓ketone formationMuscle↑uptake of glucose↑uptake of amino acids↑uptake of ketone↑uptake of potassium↑glycolysis↑synthesis of glycogen↑synthesis of protein↓protein catabolism↓release of amino acidsAdipose tissue↑uptake of glucose↑uptake of potassium↑storage of triglyceride

Box 1.2 Actions of glucagon

Liver↑glycogenolysis↑gluconeogenesis↑extraction of alanine↑ketogenesisNo significant peripheral action

The metabolic effects of insulin and glucagon and their relationship to glucose homeostasis are best considered in relationship to fasting and the postprandial state (Siegal and Kreisberg 1975). In both these situations it is the relative and not absolute concentrations of these hormones that are important.

Fasting (Figure 1.1a)

During fasting, insulin concentrations are reduced and glucagon increased, which maintains blood glucose concentrations in accordance with rule 1 above. The net effect is to reduce peripheral glucose utilisation, increase hepatic glucose production and to provide non-glucose fuels for tissues not entirely dependent on glucose. After a short (e.g. overnight) fast, glucose production needs to be 5–6 g/h to maintain blood glucose concentrations, with the brain using 80% of this. Glycogenolysis provides 60–80% and gluconeogenesis 20–40% of the required glucose. In prolonged fasts, glycogen becomes depleted and glucose production is primarily from gluconeogenesis, with an increasing proportion from the kidney as opposed to the liver. In extreme situations renal gluconeogenesis can contribute as much as 45% of glucose production. Thus glycogen is the short-term or ‘emergency’ fuel source (rule 2), with gluconeogenesis predominating in more prolonged fasts. The following metabolic alterations enable this increase in glucose production to occur.

Muscle: Glucose uptake and oxidative metabolism are reduced and fatty acid oxidation increased. Amino acids are released.Adipose tissue: There are reductions in glucose uptake and triglyceride storage. The increase in the activity of the enzyme hormone-sensitive lipase, results in hydrolysis of triglyceride to glycerol (a gluconeogenic precursor) and fatty acids, which can be metabolised.Liver: Increased cAMP concentrations result in increased glycogenolysis and gluconeogenesis thus increasing hepatic glucose output. The uptake of gluconeogenic precursors (i.e. amino acids, glycerol, lactate and pyruvate) is also increased. Ketone bodies are produced in the liver from fatty acids. This process is normally inhibited by insulin and stimulated by glucagon, thus the hormonal changes during fasting lead to an increase in ketone production. Fatty acids are also a metabolic fuel used by the liver as a source of energy needed for the reactions involved in gluconeogenesis.