Diabetic Neuropathy

by Gries, Friedrich A.

• ISBN13: 9783131275813
• ISBN10: 3131275812
• Edition: 1st
• Format: Hardcover
• Copyright: 2002-12-01
• Publisher: THIEME NEW YORK

Summary

Until recently, diabetic neuropathy has been a poorly understood and neglected complication of diabetes. The last few years have seen a dramatic increase in the understanding of this complex disorder. Here is the first book to present a systematic review that covers such topics as the structure and function of the nervous system, epidemiology and pathophysiology of diabetic neuropathy, and the clinical features and treatment options. It discusses the available diagnostic tools and strategies, and offers guidelines for the outpatient management of diabetic peripheral neuropathy. The book also covers the clinical, technical, and public health issues associated with neuropathy. Knowledge of diabetic neuropathy has improved dramatically in recent years-it's crucial to be familiar with the most recent clinical research on the disease. Essential reading for all internists, neurologists, endocrinologists, and related specialists who treat patients with diabetes!

Table of Contents

Diabetes Mellitus: An Introduction	p. 1
Definition	p. 1
Diagnosis	p. 1
Classification	p. 2
Epidemiology	p. 2
Type 1 Diabetes/IDDM	p. 2
Type 2 Diabetes/NIDDM	p. 3
Etiology and Pathogenesis of Diabetes	p. 4
Type 1 Diabetes	p. 4
Type 2 Diabetes	p. 5
Clinical Picture of Diabetes Mellitus	p. 9
Acute Symptoms	p. 9
Type 1 Diabetes	p. 10
Type 2 Diabetes	p. 11
Chronic Complications	p. 11
Introduction to the Pathogenesis of Microangiopathy	p. 11
Retinopathy	p. 12
Nephropathy	p. 14
Macroangiopathy	p. 16
Management of Diabetes Mellitus	p. 18
Prevention	p. 18
Treatment	p. 19
Pharmacological Treatment of Type 1 Diabetes	p. 22
Pharmacological Treatment of Type 2 Diabetes	p. 24
References	p. 28
Structure and Function of the Nervous System	p. 40
The Somatic Nervous System	p. 40
Overview	p. 40
Central Nervous System Pathways	p. 40
Peripheral Nerve, Receptors, and Spinal Cord	p. 43
Vascular Supply in the Peripheral Somatic Nervous System	p. 49
Concluding Remarks	p. 51
The Autonomic Nervous System	p. 51
Introduction	p. 51
Basic Principles	p. 51
Assessing Autonomic Activity	p. 55
Investigation of Autonomic Function	p. 55
Evaluation of Central Autonomic Activity and Function	p. 56
Additional Nonautonomic Investigations	p. 60
References	p. 62
Epidemiology of Diabetic Neuropathy	p. 64
Introduction	p. 64
Testing for Peripheral Neuropathy	p. 64
Population Selection	p. 65
How Common Is Diabetic Neuropathy?	p. 66
Distal Symmetrical Polyneuropathy	p. 66
Focal and Multifocal Neuropathies	p. 70
Cardiovascular Autonomic Neuropathy	p. 70
Gastrointestinal Neuropathy	p. 72
Erectile Dysfunction	p. 72
Etiological Factors Related to Diabetic Neuropathy	p. 73
Hyperglycemia	p. 74
Diabetes Duration	p. 74
Age	p. 75
Hypertension	p. 75
Hypoinsulinemia	p. 75
Hyperinsulinemia	p. 75
Other Risk Factors	p. 76
Genetic Factors	p. 76
Prognosis	p. 77
Distal Symmetrical Polyneuropathy	p. 77
Cardiovascular Autonomic Neuropathy	p. 77
Conclusions	p. 79
References	p. 79
Pathogenesis and Pathology of Diabetic Neuropathy	p. 83
Histopathology	p. 83
Diabetic Peripheral Neuropathy	p. 83
Hyperglycemia-Induced Histopathology	p. 83
Relationship of Histopathology to Type of Diabetic Neuropathy	p. 87
Diabetic Autonomic Neuropathy	p. 87
Neuropathology of Clinical Diabetic Autonomic Neuropathy	p. 87
Experimental Diabetic Autonomic Neuropathy	p. 89
Pathogenetic Mechanisms	p. 91
Pathobiochemistry and Pathophysiology	p. 91
Glycemic Control	p. 91
Introduction	p. 91
Rapidly Reversible Nerve Dysfunction After Correction of Metabolic Derangement	p. 92
Role of Intensive Diabetes Therapy in Treatment and Prevention of Diabetic Neuropathy	p. 92
Is There a Glycemic Threshold for the Risk of Diabetic Complications?	p. 96
Conclusions	p. 96
Metabolic Alterations in Experimental Models	p. 96
Introduction	p. 96
The Polyol Pathway and the Na+, K+-ATPase Defect	p. 97
Role of Nonenzymatic Glycation	p. 98
Role of Oxidative Stress and Alterations in Blood Flow	p. 99
Role of Essential Fatty Acids	p. 100
Role of Neurotrophic Factors	p. 100
Neuropathy Associated with Hyperinsulinemia and Hypoglycemia	p. 101
Physiologic Role of Proinsulin C-Peptide	p. 102
Relationships Between Metabolic Alterations and Structural Pathology in Type 1 and Type 2 Diabetic Neuropathy	p. 102
Future Directions	p. 105
Summary	p. 105
Glycation and Advanced Glycation Reactions	p. 105
Introduction	p. 105
Maillard Reaction Products	p. 106
Diabetic Neuropathy	p. 109
Conclusions	p. 112
Polyolpathway: Aldose Reductase Inhibitors--Hope for the Future?	p. 112
Introduction	p. 112
Pathophysiology	p. 112
Therapy	p. 113
Summary	p. 115
Nerve Blood Flow	p. 115
Introduction	p. 115
Nerve Blood Flow in Diabetic Patients	p. 115
Nerve Axon Reflex	p. 118
Blood Vessel Morphology in Diabetic Nerves	p. 119
Treatments to Test the Vascular Hypothesis in Peripheral Diabetic Neuropathy	p. 119
Importance of Neuron Cell Bodies	p. 122
Oxidative Stress: An Integrative View	p. 123
Introduction	p. 123
Presence of Oxidative Stress in Human and Experimental Diabetes	p. 123
Free Radical Defenses Are Reduced in Peripheral Nerve	p. 124
Reduced Oxygen Species Are Increased in experimental diabetic neuropathy	p. 125
Changes in Pro-oxidant Status	p. 127
Neural Targets of Oxidant Stress	p. 127
Synthesis of Pathogenetic Hypothesis	p. 127
Concluding Thoughts	p. 128
Neurotrophic Factors	p. 129
Introduction	p. 129
Insulin and IGFs as Neurotrophic Factors	p. 134
Neuroimmunophilins	p. 140
Programmed Cell Death and Neuropathy	p. 140
Glutamate Neurotoxicity and Its Prevention	p. 141
NAAGS in Diabetic Neuropathy	p. 142
Therapeutic Potential for Growth Factors	p. 142
Caveats on the Use of Neurotrophic Factors in the Clinic	p. 143
Autoimmunity	p. 144
Introduction	p. 144
Autoimmunity and the Nervous System	p. 144
Conclusions	p. 148
References	p. 148
Clinical Features and Treatment of Diabetic Neuropathy	p. 170
Severity and Staging of Diabetic Polyneuropathy	p. 170
Why Quantitate the Severity of Diabetic Polyneuropathy?	p. 170
How Is Severity of Diabetic Polyneuropathy to Be Judged?	p. 170
Minimum Criteria for the Diagnosis of Diabetic Neuropathy	p. 170
Can Neuropathic Abnormalities Be Demonstrated in Patients Who Do not Fulfill Minimum Criteria for Diabetic Polyneuropathy?	p. 171
Severity of Neuropathic Symptoms	p. 171
Continuous Measures of Neuropathic Impairment	p. 172
Composite Scores for Diabetic Polyneuropathy Severity	p. 172
Staging Severity of Diabetic Polyneuropathy	p. 174
Classification of the Diabetic Neuropathies	p. 175
Hyperglycemic Neuropathy	p. 175
Diabetic Distal Sensory or Sensorimotor Polyneuropathy	p. 176
Acute Painful Diabetic Neuropathy	p. 176
Autonomic Neuropathy	p. 176
Acute Motor Neuropathy	p. 176
Focal and Multifocal Neuropathies	p. 176
Cranial Neuropathies	p. 176
Thoracolumbar Radiculoneuropathy	p. 176
Proximal Diabetic Neuropathy	p. 177
Focal Limb Nerve Lesions	p. 177
Superimposed Chronic Inflammatory Demyelinating Polyneuropathy	p. 177
Hypoglycemic Neuropathy	p. 177
Diabetic Sensorimotor Neuropathy: Methods of Assessment	p. 177
Electrophysiologic Testing	p. 177
Introduction to Electrophysiology	p. 177
Nerve Conduction Studies in Neuropathies: An Overview	p. 178
Axonal Neuropathies: Diabetic Neuropathy as the Prototype	p. 178
Methodology	p. 181
Limitations	p. 184
Summary	p. 184
Quantitative Sensory Testing	p. 184
Introduction	p. 184
Pathophysiology Underlying the Elevation of Sensory Thresholds	p. 185
Methodology	p. 186
Vibration Perception Threshold	p. 187
Thermal Perception Threshold	p. 188
Simple Devices	p. 188
Epidemiologic Studies and Multicenter Clinical Trials	p. 189
Limitations of QST in the Assessment of Diabetic Neuropathy	p. 189
Motor Function	p. 189
Introduction	p. 189
Muscle Strength	p. 190
Visualization and Quantification of Striated Muscle	p. 193
Conclusions	p. 194
Unmyelinated Nerves: Skin Biopsy and Skin Blister Methods	p. 194
Introduction	p. 194
Biopsy/Blister Procedures, Staining, and Imaging	p. 195
Quantitation of Nerves in a Skin Biopsy and Blister	p. 197
Cutaneous Nerves in Diabetic Neuropathy	p. 197
Advantages of Skin Biopsy/Blister Methods	p. 197
When and Where to Biopsy/Blister	p. 198
ENF Density and Sensation	p. 198
Conclusion	p. 198
Diabetic Sensorimotor Neuropathy: Clinical Features	p. 199
Symmetric Distal Polyneuropathy	p. 199
Definition	p. 199
Clinical Picture	p. 199
Differential Diagnosis	p. 201
Focal and Multifocal Neuropathies	p. 202
Cranial Neuropathies	p. 202
Diabetic Truncal Radiculoneuropathy	p. 203
Lumbosacral Radiculoplexus Neuropathy	p. 203
Focal or Multifocal Limb Neuropathies	p. 204
Treatment	p. 204
Central Diabetic Neuropathy	p. 205
Cognitive Functioning	p. 205
Type 1 Diabetes	p. 205
Type 2 Diabetes	p. 205
Diabetes, Hyperinsulinemia, and Impaired Glucose Tolerance in the Elderly	p. 205
Neurophysiologic Findings	p. 206
Evoked Potentials	p. 206
Event-Related Potentials	p. 206
Structural Cerebral Changes	p. 206
Pathobiochemistry	p. 206
Links with Peripheral Neuropathy	p. 207
Interaction with Brain Aging	p. 207
Cerebrovascular Alterations	p. 207
Clinical Management	p. 207
Diabetic Sensorimotor Neuropathy: Treatment	p. 208
Mechanisms of Neuropathic Pain	p. 208
Pain in Distal Focal or Multifocal Diabetic Neuropathy	p. 208
Pain in Diabetic Polyneuropathy	p. 208
Mechanisms of Pain in Diabetic Neuropathy	p. 208
Nerve Trunk Pain	p. 209
Dysesthetic Pain	p. 209
Peripheral Blood Flow	p. 210
Glycemic Control	p. 210
CNS Change Secondary to Damage to the Peripheral Nervous System	p. 210
Treatment of Neuropathic Pain	p. 211
Introduction	p. 211
Neuropathic Pain	p. 211
Clinical Features of Painful Diabetic Neuropathies	p. 212
Diffuse Polyneuropathies	p. 212
Measures of Neuropathic Pain	p. 213
Treatment of Painful Diabetic Neuropathy	p. 214
Symptomatic Nonpharmacologic Treatment	p. 224
Conclusions	p. 224
Diabetic Autonomic Neuropathy	p. 225
Cardiovascular System	p. 225
Introduction	p. 225
Epidemiology, Risk Factors, and Prognosis	p. 225
Clinical Features	p. 225
Assessment	p. 228
Clinical Impact	p. 240
Respiratory Tract	p. 241
Introduction	p. 241
Abnormalities of Respiration	p. 242
Gastrointestinal Tract	p. 246
Introduction	p. 246
Pathophysiology of Disordered Gut Motility	p. 246
Impact of Gastrointestinal Motility on Glycemic Control	p. 247
Gastrointestinal Symptoms	p. 248
Conclusion	p. 262
Urogenital System	p. 262
Introduction	p. 262
Erectile Dysfunction	p. 263
Oral Agents	p. 268
Local Pharmacotherapy	p. 271
Vacuum Devices	p. 272
Penile Reconstructive Surgery	p. 272
Prosthetic Surgery	p. 272
Bladder Dysfunction	p. 272
Sudomotor Function	p. 274
Normal Sweat Response	p. 274
Tests of Sudomotor Function	p. 275
Pupillary Function	p. 278
Introduction	p. 278
Anatomy and Physiology	p. 278
Pupillary Autonomic Dysfunction in Diabetic Neuropathy	p. 282
Endocrine Regulation in Response to Physiologic Maneuvers	p. 283
Physical Exercise	p. 283
Orthostatic Hypotension	p. 285
Treatment	p. 286
Response to Hypoglycemia	p. 286
Introduction	p. 286
Physiology of Responses to Hypoglycemia	p. 287
Definition of Hypoglycemia	p. 287
Pathophysiology of Hypoglycemia in Type 1 Diabetes	p. 287
Role of Recurrent Preceding Hypoglycemia in Responses to Hypoglycemia in Diabetic Autonomic Neuropathy	p. 290
Contribution of Diabetic Autonomic Neuropathy Per Se to Reduced Plasma Epinephrine Responses to Hypoglycemia in Type 1 Diabetes	p. 293
Conclusions	p. 293
The Diabetic Foot	p. 296
Introduction	p. 296
Epidemiology and Economic Aspects	p. 296
Etiopathogenesis of Diabetic Foot Lesions	p. 297
Sensorimotor Neuropathy	p. 297
Autonomic Neuropathy	p. 297
Other Risk Factors	p. 297
Pathway to Ulceration	p. 298
Complex Causality	p. 298
The Patient with Sensory Loss	p. 299
Prevention of Diabetic Foot Ulcers	p. 300
Screening	p. 300
Semmes-Weinstein Monofilaments	p. 300
Vibration Perception Threshold and Thermal Threshold	p. 300
Interventions for High Risk Patients	p. 300
Education	p. 300
Podiatry/Chiropody	p. 301
Footwear/Orthoses/Hosiery	p. 301
Silicone	p. 301
Diabetic Charcot Neuroarthropathy	p. 301
Foot Ulcers: Diagnosis and Management	p. 303
Foot Ulcer Classification	p. 303
Wound Healing in Diabetes	p. 304
Off-Loading	p. 304
Dressings	p. 305
Management of Infection	p. 305
Other Therapies	p. 307
Prediction of Outcome	p. 307
The Team Approach	p. 308
Special Syndromes	p. 308
Insulin, Hypoglycemia, and Peripheral Neuropathy	p. 308
Introduction	p. 308
Hypoglycemic Neuropathy	p. 308
Insulin Neuritis (Acute Painful Neuropathy of Rapid Glycemic Control)	p. 310
Implications for Diabetic Neuropathy	p. 312
Ketosis-Related Neuropathy	p. 312
Introduction	p. 312
Diabetic Ketoacidosis-Associated Neuropathy	p. 312
Models of Ketoacidotic Neuropathy	p. 314
Diabetic Acute Motor Neuropathy	p. 315
Introduction	p. 315
Acute or Subacute Distal Motor Neuropathy	p. 315
Diabetic Proximal Motor Neuropathy	p. 315
Diabetic Motor Mononeuropathies	p. 315
Evaluation of Drug Effects	p. 315
Introduction	p. 316
Classification, Diagnosis, and Staging	p. 316
Relevant Outcome Measures in Controlled Clinical Trials	p. 317
Problems Related to the Use of Surrogate Variables	p. 317
Clinical Measures	p. 318
Electrodiagnostic Measures	p. 318
Quantitative Sensory Testing	p. 319
Morphologic Analysis	p. 319
Autonomic Function Tests	p. 319
Symptomatic Pain Treatment	p. 319
Natural History	p. 319
Sample Size and Duration of Trials	p. 320
Reproducibility	p. 321
Factors Confounding Treatment Effects	p. 323
Measures of Relevant Treatment Effects	p. 324
Definitions of Clinically Relevant Treatment Effects	p. 324
Presentation of Treatment Effects	p. 324
Statistical Evaluation of RCTs	p. 326
Reporting of RCTs	p. 327
Problems of Meta-analysis of Trials for the Treatment of Diabetic Neuropathy	p. 327
External Validity of RCT Results	p. 328
Conclusions	p. 329
References	p. 330
Socioeconomic Aspects	p. 361
Direct Costs of Diabetic Neuropathy	p. 361
Costs of Medical Care For Diabetic Neuropathy	p. 361
Costs of Medication	p. 361
Potential Cost Savings by Prevention of Diabetic Neuropathy	p. 362
Methodologic Considerations	p. 362
Costs of Foot Ulcer and Lower-Extremity Amputation	p. 362
Cost-of-Illness Studies: Data Sources	p. 363
Center-Based Studies	p. 363
Databases (Health Insurance Companies)	p. 363
Hospital-Based Studies	p. 365
Further Studies on Costs of Diabetic Foot Complications	p. 366
Economic Modeling: Benefits of Prevention	p. 367
Cost-Effective Treatment of Diabetic Foot Ulcers	p. 367
Conclusions	p. 368
Indirect Consequences: Disability and Premature Death	p. 368
Socioeconomic Status, Diabetic Neuropathy, and Foot Ulcer	p. 368
Health-Related Quality of Life and Diabetic Neuropathy	p. 369
Quality of Life and Peripheral Neuropathy	p. 369
Quality of Life, Foot Ulcer, and Amputation	p. 370
Psychological Aspects of Preventive Care	p. 370
Burden to the Patient	p. 370
References	p. 371
Recommendations for Structured Care	p. 373
Introduction	p. 373
Outpatient Diabetes Care	p. 373
Screening and Early Detection of Diabetic Neuropathy	p. 374
Outpatient Care of Diabetic Neuropathy	p. 374
References	p. 376
Guidelines for the Diagnosis and Outpatient Management of Diabetic Peripheral Neuropathy	p. 378
Definition	p. 378
Assessment as Part of the Annual Review of the Patient	p. 378
Management	p. 379
International Guide on the Outpatient Management of Diabetic Peripheral Neuropathy	p. 379
Introduction	p. 379
Peripheral Neuropathy in Diabetes	p. 380
Definitions	p. 381
Stages of Neuropathy	p. 381
Assessment	p. 381
Patient History	p. 381
Examination of the Patient	p. 382
Other Investigations	p. 382
The "At Risk" Foot	p. 382
Management	p. 382
No Clinical Neuropathy (Stage 0/1)	p. 383
Clinical Neuropathy (Stage 2)	p. 383
Late Complications of Clinical Neuropathy (Stage 3)	p. 383
Patient Education	p. 384
Who Should Provide Patient Education?	p. 384
What methods should be used?	p. 384
What elements should the education programme contain?	p. 384
Summary of the Management of Neuropathy	p. 385
Acknowledgement	p. 385
List of Participants	p. 385
Pilot Working Party, Brussels, Belgium 13 April 1995	p. 385
Full Working Party, London, UK, 20-22 October 1995	p. 385
Index	p. 386
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