Diabetes and the Nervous System - 1st Edition - ISBN: 9780444534804, 9780444635419

Diabetes and the Nervous System, Volume 126

1st Edition

Editors: Douglas Zochodne Rayaz Malik
Hardcover ISBN: 9780444534804
eBook ISBN: 9780444635419
Imprint: Elsevier
Published Date: 10th December 2014
Page Count: 640
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Table of Contents

  • Handbook of Clinical Neurology 3rd Series
  • Foreword
  • Preface
  • Section 1: Clinical impact of diabetes on the nervous system
    • Chapter 1: Epidemiology of polyneuropathy in diabetes and prediabetes
      • Abstract
      • Introduction
      • Testing for peripheral neuropathy
      • Painful neuropathy
      • Population selection
      • Prevalence in diabetes
      • Prevalence in prediabetes
      • Incidence and natural history of diabetic polyneuropathy
      • Etiologic factors related to diabetic neuropathy
      • Conclusions
    • Chapter 2: Clinical features of diabetic polyneuropathy
      • Abstract
      • Early studies of the clinical features of diabetic polyneuropathy
      • Symptoms of diabetic polyneuropathy
      • Clinical signs of diabetic polyneuropathy
      • Subtypes of diabetic polyneuropathy
      • Distinguishing diabetic polyneuropathy from other polyneuropathies
      • Conclusions
    • Chapter 3: Focal and entrapment neuropathies
      • Abstract
      • Introduction
      • Cranial mononeuropathies
      • Upper limb mononeuropathies
      • Truncal mononeuropathies
      • Lower limb mononeuropathies
      • Conclusion
    • Chapter 4: Diabetic radiculoplexus neuropathies
      • Abstract
      • Introduction
      • Clinical features of the diabetic radiculoplexus neuropathies
      • Epidemiology
      • Etiology and pathogenesis
      • Treatment
      • Conclusion
    • Chapter 5: Painful diabetic neuropathy: clinical aspects
      • Abstract
      • Introduction
      • Epidemiology of painful diabetic neuropathy
      • Pathogenesis of neuropathic pain
      • Early diagnosis and intervention in painful neuropathy
      • Symptoms and signs of painful diabetic neuropathy
      • Acute painful neuropathies
      • Natural history of painful diabetic neuropathy
      • Neuropathic pain assessment
      • Differential diagnosis of painful neuropathy
      • Diabetic painful neuropathy and autonomic dysfunction
      • Conclusions
      • Acknowledgments
    • Chapter 6: Diabetic autonomic neuropathy
      • Abstract
      • Introduction
      • Generalized autonomic neuropathy
      • Autonomic neuropathy and prediabetes
      • Treatment-induced neuropathy
      • Hypoglycemia-associated transient autonomic dysfunction
    • Chapter 7: Motor neuropathy
      • Abstract
      • Introduction
      • Motor nerve dysfunction
      • Muscle strength
      • Muscle strength in diabetes
      • Muscular atrophy
      • Muscle strength, balance, gait, and falls
      • Conclusions
    • Chapter 8: Diabetic neuropathy and foot complications
      • Abstract
      • Introduction
      • Historical aspects of diabetic neuropathy and foot complications
      • Background: the diabetic foot
      • Epidemiology and health economics of diabetic foot problems
      • Neuropathy and foot ulceration
      • Other risk factors for diabetic foot ulceration
      • Conclusions
    • Chapter 9: Glucose intolerance, metabolic syndrome, and neuropathy
      • Abstract
      • Introduction
      • Hypotheses and pathophysiology
      • Definition and prevalence of metabolic syndrome
      • Impaired glucose tolerance and impaired fasting glucose
      • Obesity and dyslipidemia
      • Clinical presentation of impaired glucose tolerance and metabolic syndrome-associated neuropathy
      • Laboratory testing for glucose dysmetabolism
      • Overview of ancillary testing
      • Outcomes and prognosis
      • Management and treatment
      • Future directions
    • Chapter 10: Diabetic neuropathy in children
      • Abstract
      • Background
      • Definition
      • Prevalence of diabetic neuropathy in children
      • Pathogenesis of diabetic neuropathy
      • Diagnosis of pediatric diabetic neuropathy
      • Risk factors for pediatric diabetic neuropathy
      • Treatment of symptomatic pediatric diabetic neuropathy
      • Effects of cointervention
      • Screening for other diabetic complications
      • Psychosocial issues related to pediatric diabetes
      • Conclusion
    • Chapter 11: Cognitive disorders in diabetic patients
      • Abstract
      • Introduction
      • Evaluation of cognitive functioning
      • Cognitive functioning in type 1 diabetes
      • Cognitive functioning in type 2 diabetes
      • Cognitive functioning in prediabetic stages
      • Consequences of cognitive dysfunction in diabetes
      • Mood disorders in diabetes
      • Brain MRI studies
      • Determinants and mechanisms
      • Treatment of cognitive dysfunction
      • Practical implications
    • Chapter 12: Stroke and diabetes mellitus
      • Abstract
      • Introductory concepts
      • Clinical features
      • Causes: stroke mechanism
      • Epidemiology and risk factors
      • Acute stroke: special considerations in diabetic patients
      • Stroke prevention: special considerations in diabetic patients
      • Conclusions
    • Chapter 13: Neurologic infections in diabetes mellitus
      • Abstract
      • Introduction
      • Viruses
      • Bacteria
      • Fungi
      • Parasitic infections in the pathogenesis of diabetes mellitus
      • Summary
    • Chapter 14: Recognition and management of psychosocial issues in diabetic neuropathy
      • Abstract
      • Introduction
      • The burden of painful diabetic neuropathy
      • Emotional side of the diabetic neuropathy experience
      • The role of psychological factors in shaping pain experience
      • Psychosocial interventions for diabetic neuropathy symptom management
      • The case for an integrated biopsychosocial approach to diabetic neuropathy symptom management
      • Measuring quality of life in diabetic neuropathy: generic, specific, or combined approach?
      • The role of psychosocial and behavioral factors in diabetic foot ulcer prevention
      • Concluding remarks
      • Acknowledgments
    • Chapter 15: General aspects of diabetes mellitus
      • Abstract
      • Diagnosis of diabetes
      • Classification of diabetes
      • Diabetes types
      • Screening for diabetes
      • The diabetic history
      • The diabetic physical examination
      • Glycemic goals
      • Diabetes pharmacotherapy
      • Management outline in newly diagnosed type 2 diabetes mellitus: an algorithm
      • Diabetes control of inpatients
      • Cerebral infarction and glycemic control
      • Enteral and parenteral nutrition and glycemic control
      • Acknowledgments
    • Chapter 16: Sexual dysfunction in diabetes
      • Abstract
      • Introduction
      • Sexual dysfunction in diabetic women
      • Sexual dysfunction in diabetic men
      • Erectile dysfunction
      • Treatment of erectile dysfunction in diabetic patients
  • Section 2: Diagnostic and therapeutic approaches to diabetic neurological complications
    • Chapter 17: Electrophysiologic testing in diabetic neuropathy
      • Abstract
      • Electrophysiologic studies: background
      • Rationale for electrophysiologic studies
      • Changes in electrophysiologic studies in diabetes
      • What is the role of electrophysiologic studies in diabetes?
      • Summary
    • Chapter 18: Pathology of human diabetic neuropathy
      • Abstract
      • Introduction
      • Nerve biopsy
      • Myelinated fibers
      • Unmyelinated fibers
      • Microvessels
      • Extracellular matrix
      • Neuropathology in variants of diabetic neuropathy
      • Skin biopsy
      • Sudomotor innervation
      • Motor abnormalities
    • Chapter 19: Epidermal innervation in diabetes
      • Abstract
      • Introduction
      • An overview of skin innervation
      • Quantitation of epidermal fibers
      • Skin biopsy as a diagnostic test in small Fiber sensory neuropathies
      • Evaluation of epidermal fibers in diabetic neuropathy
      • Skin biopsy as a marker for early diabetic neuropathy
      • Skin biopsy as a biomarker of neuropathic pain
      • Morphologic features of epidermal nerve fibers
      • Epidermal innervation in clinical trials
      • Cutaneous autonomic nerve fiber innervation in diabetes
      • Regeneration of epidermal nerve fibers in diabetic neuropathy
    • Chapter 20: Clinical and diagnostic features of small fiber damage in diabetic polyneuropathy
      • Abstract
      • Introduction
      • Clinical features
      • Diagnostic criteria
      • Differential diagnosis
      • Diagnostic tests
      • Conclusion
    • Chapter 21: Central nervous system imaging in diabetic cerebrovascular diseases and white matter hyperintensities
      • Abstract
      • Introduction
      • Stroke in patients with diabetes mellitus
      • Imaging techniques in patients with diabetes mellitus-related chronic cerebrovascular disorders
      • Conclusions
    • Chapter 22: Therapy for diabetic neuropathy: an overview
      • Abstract
      • Introduction
      • Treatment strategies for preventing neuropathy
      • Symptomatic treatment strategies
      • New treatment strategies
      • Summary
    • Chapter 23: Methodology for conduct of epidemiologic surveys and randomized controlled trials of diabetic polyneuropathy
      • Abstract
      • Reasons why epidemiologic surveys and randomized controlled clinical trials of diabetic polyneuropathy are difficult
      • Choice of neuropathy end points
      • Single versus composite outcome measurements in epidemiologic surveys or randomized controlled trials
      • Reference values of neurophysiologic end points
      • Proficiency and neurophysiologic test and clinical assessment
  • Section 3: Fundamental studies of diabetic neuroscience
    • Chapter 24: Neuroscience of glucose homeostasis
      • Abstract
      • Introduction
      • Daily rhythm in plasma glucose concentrations
      • The role of the hypothalamic output to the autonomic nervous system in the 24 hour rhythm in plasma glucose concentrations
      • Brain areas and neuropeptides important for glucose metabolism
      • Central nervous system control of hormones influencing glucose metabolism
    • Chapter 25: Mechanisms of disease: Mitochondrial dysfunction in sensory neuropathy and other complications in diabetes
      • Abstract
      • Overview of diabetic neuropathy
      • Role of oxidative stress in neurodegeneration in diabetes
      • Calcium dysfunction in diabetic neuropathy
      • Impaired mitochondrial function in pathogenesis of type 2 diabetes and other complications
      • Aberrant mitochondrial bioenergetics in diabetic neuropathy
      • Conclusions
      • Acknowledgments
    • Chapter 26: Mechanisms of diabetic neuron damage: Molecular pathways
      • Abstract
      • Introduction
      • How are neurons targeted by diabetic polyneuropathy?
      • What mechanisms target neurons?
      • Conclusions: linking diverse pathways of neuropathy development
      • Acknowledgments
    • Chapter 27: Mechanisms of diabetic neuropathy: Schwann cells
      • Abstract
      • Introduction
      • Schwann cell development
      • Schwann cell structure
      • Schwann cell function
      • Diabetic neuropathy
      • Schwann cells and pathogenic mechanisms
      • Conclusions
    • Chapter 28: Mechanisms of diabetic neuropathy: axon dysfunction
      • Abstract
      • Introduction
      • Structural changes
      • Underlying metabolic mechanisms
      • Concluding remarks
    • Chapter 29: Mechanisms of disease: role of neurotrophins in diabetes and diabetic neuropathy
      • Abstract
      • Introduction
      • Neurotrophins: complexities to consider
      • Neurotrophins and metabolism: a special role for brain-derived neurotrophic factor
      • Failure of human trials
      • Therapeutic strategies to improve neurotrophin support
      • Acknowledgments
    • Chapter 30: Experimental motor neuropathy in diabetes
      • Abstract
      • Introduction
      • Motor nerve conduction velocity in experimental models of diabetic neuropathy
      • Pathologic changes in motor neurons in experimental models
      • Diabetes-induced effects on skeletal muscle cells
      • Sensory dysfunction in feedback from muscle
      • Considerations for improved models to study motor dysfunction in diabetes
      • Conclusions
    • Chapter 31: Ischemia and diabetic neuropathy
      • Abstract
      • Introduction
      • Experimental ischemic neuropathy
      • Ischemia and diabetic nerve
      • Ischemia and endoneurial hypoxia in diabetic polyneuropathy
      • Ischemia in other diabetic neuropathies
    • Chapter 32: Diabetes and neurodegeneration in the brain
      • Abstract
      • Introduction
      • Links between Alzheimer disease and diabetes
      • Alzheimer disease pathology and pathophysiology
      • Pathologic manifestations of Alzheimer disease and relationships to diabetic encephalopathy
      • Diabetic encephalopathy pathology and pathophysiology
      • Clinical manifestations in diabetic subjects
      • Risk factors for impaired cognition and dementia in diabetes
      • Risk of dementia with diabetes
      • Cerebrovascular disease and development of diabetic encephalopathy
      • The role of animal models in understanding diabetic encephalopathy
      • The role of brain imaging in diabetic encephalopathy
      • Potential pharmacologic targets in diabetic encephalopathy
      • Summary and future directions
    • Chapter 33: Neurologic damage in hypoglycemia
      • Abstract
      • Introduction
      • On hypoglycemia and central nervous system damage
      • On hypoglycemia and peripheral nervous system damage
      • Possible cellular mechanisms of neurologic damage in hypoglycemia
      • Conclusions
    • Chapter 34: Painful neuropathy: Mechanisms
      • Abstract
      • Painful diabetic neuropathy
      • Animal models of painful diabetic neuropathy
      • Mechanisms of painful diabetic neuropathy
      • Mechanism-targeted therapies
      • Conclusions and speculation
      • Acknowledgments
    • Chapter 35: Insights into the pathogenesis and treatment of painful diabetic neuropathy
      • Abstract
      • Introduction
      • Painful diabetic peripheral neuropathy
      • Pathogenesis of painful diabetic peripheral neuropathy
      • Magnetic resonance imaging of the central nervous system in painful diabetic peripheral neuropathy
      • Future role of neuroimaging in painful diabetic peripheral neuropathy
      • Conclusion
    • Chapter 36: Autonomic neuropathy in experimental models of diabetes mellitus
      • Abstract
      • Experimental diabetic autonomic neuropathy
      • Proposed pathogenetic mechanisms of diabetic autonomic neuropathy
      • Summary
  • Index


This is a unique compilation, by experts worldwide, addressing how diabetes impacts the nervous system. For example, diabetic polyneuropathy, a disorder more common than MS, Parkinson’s disease, and ALS combined, is a major source of disability to diabetic persons worldwide. This book addresses diabetic polyneuropathy and how diabetes alters other parts of the nervous system.

Key Features

  • Offers a unique emphasis on the neurological manifestations of diabetes
  • Provides thorough coverage of the clinical, experimental, mechanistic, therapeutic, peripheral, and central aspects of diabetic neuropathy
  • Edited work with chapters authored by leaders in the field around the globe – the broadest, most expert coverage available


Clinical neurologists and research neuroscientists


No. of pages:
© Elsevier 2014
eBook ISBN:
Hardcover ISBN:

About the Editors

Douglas Zochodne Editor

Douglas Zochodne is a Professor with tenure at the University of Calgary in the Department of Clinical Neurosciences and the Hotchkiss Brain Institute. He trained in medicine and subsequently Neurology at the University of Western Ontario. He completed fellowships in Neuromuscular disease with Dr. Charles Bolton at Western and Drs. Phillip Low and Peter Dyck at Mayo Clinic. He served on faculty at Queen’s University, Ontario Canada then subsequently at the University of Calgary where he has worked since 1992. He is a consultant Neurologist of Alberta Health Services, Calgary zone and serves as the Director of the Neuromuscular Clinic (Adult), University of Calgary and as Director of Clinical Neurophysiology (Adult EMG). Dr. Zochodne served as Editor-in-Chief of the Canadian Journal of Neurological Sciences from 1999-2007 and President of the Peripheral Nerve Society from 2009-2011. His research laboratory has been externally funded since 1988 by CIHR, CDA, JDRF, NIH and other agencies. He has published work focused on the peripheral neurobiology of regeneration, experimental diabetic neuropathy and clinical neuropathies and has authored over 240 original articles, chapters and books. He was awarded the Wolfe Prize in Neuropathy Research by the American Neurological Association in 2011. His more recent papers, published in the Journal of Neuroscience, Brain and Nature Communications, identifies roles for tumour suppressor proteins in enhancing adult neuron regeneration. He has recently accepted an offer to Chair the Division of Neurology at the University of Alberta and will be moving with his laboratory to take up this new role in July 2014.

Affiliations and Expertise

Department of Clinical Neurosciences and the Hotchkiss Brain Institute, University of Calgary, Calgary, Canada

Rayaz Malik Editor

Rayaz A. Malik is a Professor of Medicine at Weill Cornell Medical College, Qatar and Honorary Professor of Medicine and Consultant Physician in the Centre for Endocrinology and Diabetes, Central Manchester University Teaching Hospitals Foundation Trust and University of Manchester. He obtained his BSc., MSc. and MB ChB from the University of Aberdeen and his PhD from the University of Manchester. He is an expert in the pathogenesis, assessment and treatment of diabetic neuropathy and has been a co-editor for three books, co-authored over 30 book chapters and published (~130 peer reviewed papers) and presented (~500 national and international presentations) extensively. His research is funded by the NIH, JDRF, DUK, BHF and EU and his funding totals ~$8M. He was the Chairman of Neurodiab, the international study group of the EASD for Diabetic Neuropathy (2009-2012). He won the young clinical investigator prize for clinical science for Neurodiab in 1999, North West of England Medical Society Prize in 2000; North East Medical Society Prize 2012. He has been an invited lecturer for the American Diabetes Association 2003, 2007 and 2010, 2012, 2013; European Association for the Study of Diabetes 2004, 2007, 2008, 2010, 2012 and 2013 and World Diabetes Congress 2009, 2011, 2013. He is an associate editor for Diabetic Medicine (2006 to present); BMC Neurology (2009-present); Advances in Therapy (2009-present) and is on the editorial board for Journal of Diabetes and Its Complications (2012-present) and Journal of Diabetes Investigation (2012-present).

Affiliations and Expertise

Centre for Endocrinology & Diabetes, Institute of Human Development, University of Manchester, Manchester, UK