Diabetic Neuropathy

by Gries, Friedrich A.; Cameron, Norman E.; Low, Phillip A.; Ziegler, Dan; Andersen, Henning

• ISBN13: 9781588900050
• ISBN10: 1588900053
• Edition: 1st
• Format: Hardcover
• Copyright: 2003-02-01
• Publisher: Thieme Medical Pub

Summary

Awareness of neuropathy as a chronic complication of diabetes is constantly increasing. Diabetes centers adopt methods to diagnose neuropathy without neurological training. This trend calls for instructions on how to use and interpret diagnostic methods. This book includes recent research and covers clinical, technical, and public health aspects of neuropathy, bringing together the top experts in the field.

Table of Contents

Diabetes Mellitus: An Introduction	1	(39)
F.A. Gries
J. Eckel
P. Rosen
D. Ziegler
Definition	1	(1)
Diagnosis	1	(1)
Classification	2	(1)
Epidemiology	2	(2)
Type 1 Diabetes/IDDM	2	(1)
Type 2 Diabetes/NIDDM	3	(1)
Etiology and Pathogenesis of Diabetes	4	(5)
Type 1 Diabetes	4	(1)
Type 2 Diabetes	5	(4)
Clinical Picture of Diabetes Mellitus	9	(9)
Acute Symptoms	9	(1)
Type 1 Diabetes	10	(1)
Type 2 Diabetes	11	(1)
Chronic Complications	11	(1)
Introduction to the Pathogenesis of Microangiopathy	11	(1)
Retinopathy	12	(2)
Nephropathy	14	(2)
Macroangiopathy	16	(2)
Management of Diabetes Mellitus	18	(10)
Prevention	18	(1)
Treatment	19	(3)
Pharmacological Treatment of Type 1 Diabetes	22	(2)
Pharmacological Treatment of Type 2 Diabetes	24	(4)
References	28	(12)
Structure and Function of the Nervous System	40	(24)
The Somatic Nervous System	40	(11)
N. E. Cameron
Overview	40	(1)
Central Nervous System Pathways	40	(3)
Peripheral Nerve, Receptors, and Spinal Cord	43	(6)
Vascular Supply in the Peripheral Somatic Nervous System	49	(2)
Concluding Remarks	51	(1)
The Autonomic Nervous System	51	(11)
C.J. Mathias
Introduction	51	(1)
Basic Principles	51	(4)
Assessing Autonomic Activity	55	(1)
Investigation of Autonomic Function	55	(1)
Evaluation of Central Autonomic Activity and Function	56	(4)
Additional Nonautonomic Investigations	60	(2)
References	62	(2)
Epidemiology of Diabetic Neuropathy	64	(19)
J.E. Shaw
P.Z. Zimmet
F.A. Gries
D. Ziegler
Introduction	64	(2)
Testing for Peripheral Neuropathy	64	(1)
Population Selection	65	(1)
How Common Is Diabetic Neuropathy?	66	(11)
Distal Symmetrical Polyneuropathy	66	(4)
Focal and Multifocal Neuropathies	70	(1)
Cardiovascular Autonomic Neuropathy	70	(2)
Gastrointestinal Neuropathy	72	(1)
Erectile Dysfunction	72	(1)
Etiological Factors Related to Diabetic Neuropathy	73	(1)
Hyperglycemia	74	(1)
Diabetes Duration	74	(1)
Age	75	(1)
Hypertension	75	(1)
Hypoinsulinemia	75	(1)
Hyperinsulinemia	75	(1)
Other Risk Factors	76	(1)
Genetic Factors	76	(1)
Prognosis	77	(2)
Distal Symmetrical Polyneuropathy	77	(1)
Cardiovascular Autonomic Neuropathy	77	(2)
Conclusions	79	(1)
References	79	(4)
Pathogenesis and Pathology of Diabetic Neuropathy	83	(87)
Histopathology	83	(1)
Diabetic Peripheral Neuropathy	83	(4)
A.P. Mizisin
H.C. Powell
Hyperglycemia-Induced Histopathology	83	(4)
Relationship of Histopathology to Type of Diabetic Neuropathy	87	(1)
Diabetic Autonomic Neuropathy	87	(4)
R.E. Schmidt
Neuropathology of Clinical Diabetic Autonomic Neuropathy	87	(2)
Experimental Diabetic Autonomic Neuropathy	89	(2)
Pathogenetic Mechanisms	91	(1)
Pathobiochemistry and Pathophysiology	91	(1)
Glycemic Control	91	(5)
D. Ziegler
Introduction	91	(1)
Rapidly Reversible Nerve Dysfunction After Correction of Metabolic Derangement	92	(1)
Role of Intensive Diabetes Therapy in Treatment and Prevention of Diabetic Neuropathy	92	(4)
Is There a Glycemic Threshold for the Risk of Diabetic Complications?	96	(1)
Conclusions	96	(1)
Metabolic Alterations in Experimental Models	96	(9)
A.A.F. Sima
C.R. Pierson
Introduction	96	(1)
The Polyol Pathway and the Na+, K+-ATPase Defect	97	(1)
Role of Nonenzymatic Glycation	98	(1)
Role of Oxidative Stress and Alterations in Blood Flow	99	(1)
Role of Essential Fatty Acids	100	(1)
Role of Neurotrophic Factors	100	(1)
Neuropathy Associated with Hyperinsulinemia and Hypoglycemia	101	(1)
Physiologic Role of Proinsulin C-Peptide	102	(1)
Relationships Between Metabolic Alterations and Structural Pathology in Type 1 and Type 2 Diabetic Neuropathy	102	(3)
Future Directions	105	(1)
Summary	105	(1)
Glycation and Advanced Glycation Reactions	105	(7)
J.W. Baynes
Introduction	105	(1)
Maillard Reaction Products	106	(3)
Diabetic Neuropathy	109	(3)
Conclusions	112	(1)
Polyolpathway: Aldose Reductase Inhibitors--Hope for the Future?	112	(3)
E.L. Feldman
K.A. Sullivan
M.J. Stevens
Introduction	112	(1)
Pathophysiology	112	(1)
Therapy	113	(2)
Summary	115	(1)
Nerve Blood Flow	115	(1)
M.A. Cotter
A. Veves
S. Tesfaye
N.E. Cameron
Introduction	115	(1)
Nerve Blood Flow in Diabetic Patients	115	(3)
Nerve Axon Reflex	118	(1)
Blood Vessel Morphology in Diabetic Nerves	119	(1)
Treatments to Test the Vascular Hypothesis in Peripheral Diabetic Neuropathy	119	(3)
Importance of Neuron Cell Bodies	122	(1)
Oxidative Stress: An Integrative View	123	(1)
P.A. Low
Introduction	123	(1)
Presence of Oxidative Stress in Human and Experimental Diabetes	123	(1)
Free Radical Defenses Are Reduced in Peripheral Nerve	124	(1)
Reduced Oxygen Species Are Increased in experimental diabetic neuropathy	125	(2)
Changes in Pro-oxidant Status	127	(1)
Neural Targets of Oxidant Stress	127	(1)
Synthesis of Pathogenetic Hypothesis	127	(1)
Concluding Thoughts	128	(1)
Neurotrophic Factors	129	(15)
A. Vinik
G. Pittenger
K. Stansberry
T.S. Park
T. Erbas
M. Skeen
Introduction	129	(5)
Insulin and IGFs as Neurotrophic Factors	134	(6)
Neuroimmunophilins	140	(1)
Programmed Cell Death and Neuropathy	140	(1)
Glutamate Neurotoxicity and Its Prevention	141	(1)
NAAGS in Diabetic Neuropathy	142	(1)
Therapeutic Potential for Growth Factors	142	(1)
Caveats on the Use of Neurotrophic Factors in the Clinic	143	(1)
Autoimmunity	144	(4)
P.J. Watkins
G. Sundkvist
Introduction	144	(1)
Autoimmunity and the Nervous System	144	(4)
Conclusions	148	(1)
References	148	(22)
Clinical Features and Treatment of Diabetic Neuropathy	170	(191)
Severity and Staging of Diabetic Polyneuropathy	170	(1)
P.J. Dyck
Why Quantitate the Severity of Diabetic Polyneuropathy?	170	(1)
How Is Severity of Diabetic Polyneuropathy to Be Judged?	170	(1)
Minimum Criteria for the Diagnosis of Diabetic Neuropathy	170	(1)
Can Neuropathic Abnormalities Be Demonstrated in Patients Who Do not Fulfill Minimum Criteria for Diabetic Polyneuropathy?	171	(1)
Severity of Neuropathic Symptoms	171	(1)
Continuous Measures of Neuropathic Impairment	172	(1)
Composite Scores for Diabetic Polyneuropathy Severity	172	(2)
Staging Severity of Diabetic Polyneuropathy	174	(1)
Classification of the Diabetic Neuropathies	175	(1)
P.K. Thomas
Hyperglycemic Neuropathy	175	(1)
Diabetic Distal Sensory or Sensorimotor Polyneuropathy	176	(1)
Acute Painful Diabetic Neuropathy	176	(1)
Autonomic Neuropathy	176	(1)
Acute Motor Neuropathy	176	(1)
Focal and Multifocal Neuropathies	176	(1)
Cranial Neuropathies	176	(1)
Thoracolumbar Radiculoneuropathy	176	(1)
Proximal Diabetic Neuropathy	177	(1)
Focal Limb Nerve Lesions	177	(1)
Superimposed Chronic Inflammatory Demyelinating Polyneuropathy	177	(1)
Hypoglycemic Neuropathy	177	(1)
Diabetic Sensorimotor Neuropathy: Methods of Assessment	177	(1)
Electrophysiologic Testing	177	(7)
V. Bril
Introduction to Electrophysiology	177	(1)
Nerve Conduction Studies in Neuropathies: An Overview	178	(1)
Axonal Neuropathies: Diabetic Neuropathy as the Prototype	178	(3)
Methodology	181	(3)
Limitations	184	(1)
Summary	184	(1)
Quantitative Sensory Testing	184	(5)
J.C. Arezzo
Introduction	184	(1)
Pathophysiology Underlying the Elevation of Sensory Thresholds	185	(1)
Methodology	186	(1)
Vibration Perception Threshold	187	(1)
Thermal Perception Threshold	188	(1)
Simple Devices	188	(1)
Epidemiologic Studies and Multicenter Clinical Trials	189	(1)
Limitations of QST in the Assessment of Diabetic Neuropathy	189	(1)
Motor Function	189	(5)
H. Andersen
J. Jakobsen
Introduction	189	(1)
Muscle Strength	190	(3)
Visualization and Quantification of Striated Muscle	193	(1)
Conclusions	194	(1)
Unmyelinated Nerves: Skin Biopsy and Skin Blister Methods	194	(5)
W.R. Kennedy
G. Wendelschafer-Crabb
Introduction	194	(1)
Biopsy/Blister Procedures, Staining, and Imaging	195	(2)
Quantitation of Nerves in a Skin Biopsy and Blister	197	(1)
Cutaneous Nerves in Diabetic Neuropathy	197	(1)
Advantages of Skin Biopsy/Blister Methods	197	(1)
When and Where to Biopsy/Blister	198	(1)
ENF Density and Sensation	198	(1)
Conclusion	198	(1)
Diabetic Sensorimotor Neuropathy: Clinical Features	199	(1)
Symmetric Distal Polyneuropathy	199	(3)
B. Neundorfer
P.K. Thomas
Definition	199	(1)
Clinical Picture	199	(2)
Differential Diagnosis	201	(1)
Focal and Multifocal Neuropathies	202	(3)
P.K. Thomas
Cranial Neuropathies	202	(1)
Diabetic Truncal Radiculoneuropathy	203	(1)
Lumbosacral Radiculoplexus Neuropathy	203	(1)
Focal or Multifocal Limb Neuropathies	204	(1)
Treatment	204	(1)
Central Diabetic Neuropathy	205	(1)
G.J. Biessels
W.H. Gispen
Cognitive Functioning	205	(1)
Type 1 Diabetes	205	(1)
Type 2 Diabetes	205	(1)
Diabetes, Hyperinsulinemia, and Impaired Glucose Tolerance in the Elderly	205	(1)
Neurophysiologic Findings	206	(1)
Evoked Potentials	206	(1)
Event-Related Potentials	206	(1)
Structural Cerebral Changes	206	(1)
Pathobiochemistry	206	(1)
Links with Peripheral Neuropathy	207	(1)
Interaction with Brain Aging	207	(1)
Cerebrovascular Alterations	207	(1)
Clinical Management	207	(1)
Diabetic Sensorimotor Neuropathy: Treatment	208	(1)
Mechanisms of Neuropathic Pain	208	(3)
P. K. Thomas
Pain in Distal Focal or Multifocal Diabetic Neuropathy	208	(1)
Pain in Diabetic Polyneuropathy	208	(1)
Mechanisms of Pain in Diabetic Neuropathy	208	(1)
Nerve Trunk Pain	209	(1)
Dysesthetic Pain	209	(1)
Peripheral Blood Flow	210	(1)
Glycemic Control	210	(1)
CNS Change Secondary to Damage to the Peripheral Nervous System	210	(1)
Treatment of Neuropathic Pain	211	(14)
D. Ziegler
Introduction	211	(1)
Neuropathic Pain	211	(1)
Clinical Features of Painful Diabetic Neuropathies	212	(1)
Diffuse Polyneuropathies	212	(1)
Measures of Neuropathic Pain	213	(1)
Treatment of Painful Diabetic Neuropathy	214	(10)
Symptomatic Nonpharmacologic Treatment	224	(1)
Conclusions	224	(1)
Diabetic Autonomic Neuropathy	225	(1)
Cardiovascular System	225	(16)
V. Spallone
G. Menzinger
D. Ziegler
Introduction	225	(1)
Epidemiology, Risk Factors, and Prognosis	225	(1)
Clinical Features	225	(3)
Assessment	228	(12)
Clinical Impact	240	(1)
Respiratory Tract	241	(5)
L. Scionti
P. Bottini
Introduction	241	(1)
Abnormalities of Respiration	242	(4)
Gastrointestinal Tract	246	(16)
D. O'Donovan
M. Samson
C. Feinle
K.L. Jones
M. Horowitz
Introduction	246	(1)
Pathophysiology of Disordered Gut Motility	246	(1)
Impact of Gastrointestinal Motility on Glycemic Control	247	(1)
Gastrointestinal Symptoms	248	(14)
Conclusion	262	(1)
Urogenital System	262	(12)
C.G. Stief
D. Ziegler
Introduction	262	(1)
Erectile Dysfunction	263	(5)
Oral Agents	268	(3)
Local Pharmacotherapy	271	(1)
Vacuum Devices	272	(1)
Penile Reconstructive Surgery	272	(1)
Prosthetic Surgery	272	(1)
Bladder Dysfunction	272	(2)
Sudomotor Function	274	(4)
P.A. Low
Normal Sweat Response	274	(1)
Tests of Sudomotor Function	275	(3)
Pupillary Function	278	(5)
R.H. Straub
Introduction	278	(1)
Anatomy and Physiology	278	(4)
Pupillary Autonomic Dysfunction in Diabetic Neuropathy	282	(1)
Endocrine Regulation in Response to Physiologic Maneuvers	283	(3)
J. Hilsted
M. Taskiran
Physical Exercise	283	(2)
Orthostatic Hypotension	285	(1)
Treatment	286	(1)
Response to Hypoglycemia	286	(10)
G.B. Bolli
C.G. Fanelli
F. Porcellati
S. Pampanelli
Introduction	286	(1)
Physiology of Responses to Hypoglycemia	287	(1)
Definition of Hypoglycemia	287	(1)
Pathophysiology of Hypoglycemia in Type 1 Diabetes	287	(3)
Role of Recurrent Preceding Hypoglycemia in Responses to Hypoglycemia in Diabetic Autonomic Neuropathy	290	(3)
Contribution of Diabetic Autonomic Neuropathy Per Se to Reduced Plasma Epinephrine Responses to Hypoglycemia in Type 1 Diabetes	293	(1)
Conclusions	293	(3)
The Diabetic Foot	296	(1)
A.J.M. Boulton
Introduction	296	(1)
Epidemiology and Economic Aspects	296	(1)
Etiopathogenesis of Diabetic Foot Lesions	297	(1)
Sensorimotor Neuropathy	297	(1)
Autonomic Neuropathy	297	(1)
Other Risk Factors	297	(1)
Pathway to Ulceration	298	(2)
Complex Causality	298	(1)
The Patient with Sensory Loss	299	(1)
Prevention of Diabetic Foot Ulcers	300	(1)
Screening	300	(1)
Semmes-Weinstein Monofilaments	300	(1)
Vibration Perception Threshold and Thermal Threshold	300	(1)
Interventions for High Risk Patients	300	(1)
Education	300	(1)
Podiatry/Chiropody	301	(1)
Footwear/Orthoses/Hosiery	301	(1)
Silicone	301	(1)
Diabetic Charcot Neuroarthropathy	301	(2)
Foot Ulcers: Diagnosis and Management	303	(4)
Foot Ulcer Classification	303	(1)
Wound Healing in Diabetes	304	(1)
Off-Loading	304	(1)
Dressings	305	(1)
Management of Infection	305	(2)
Other Therapies	307	(1)
Prediction of Outcome	307	(1)
The Team Approach	308	(1)
Special Syndromes	308	(1)
Insulin, Hypoglycemia, and Peripheral Neuropathy	308	(4)
S.E.M. Eaton
S. Tesfaye
Introduction	308	(1)
Hypoglycemic Neuropathy	308	(2)
Insulin Neuritis (Acute Painful Neuropathy of Rapid Glycemic Control)	310	(2)
Implications for Diabetic Neuropathy	312	(1)
Ketosis-Related Neuropathy	312	(3)
R.A. Malik
Introduction	312	(1)
Diabetic Ketoacidosis-Associated Neuropathy	312	(2)
Models of Ketoacidotic Neuropathy	314	(1)
Diabetic Acute Motor Neuropathy	315	(1)
P.A. Low
Introduction	315	(1)
Acute or Subacute Distal Motor Neuropathy	315	(1)
Diabetic Proximal Motor Neuropathy	315	(1)
Diabetic Motor Mononeuropathies	315	(1)
Evaluation of Drug Effects	315	(1)
D. Luft
D. Ziegler
Introduction	316	(1)
Classification, Diagnosis, and Staging	316	(1)
Relevant Outcome Measures in Controlled Clinical Trials	317	(9)
Problems Related to the Use of Surrogate Variables	317	(1)
Clinical Measures	318	(1)
Electrodiagnostic Measures	318	(1)
Quantitative Sensory Testing	319	(1)
Morphologic Analysis	319	(1)
Autonomic Function Tests	319	(1)
Symptomatic Pain Treatment	319	(1)
Natural History	319	(1)
Sample Size and Duration of Trials	320	(1)
Reproducibility	321	(2)
Factors Confounding Treatment Effects	323	(1)
Measures of Relevant Treatment Effects	324	(1)
Definitions of Clinically Relevant Treatment Effects	324	(1)
Presentation of Treatment Effects	324	(2)
Statistical Evaluation of RCTs	326	(1)
Reporting of RCTs	327	(1)
Problems of Meta-analysis of Trials for the Treatment of Diabetic Neuropathy	327	(1)
External Validity of RCT Results	328	(1)
Conclusions	329	(1)
References	330	(31)
Socioeconomic Aspects	361	(12)
W. Rathmann
J. Ward
Direct Costs of Diabetic Neuropathy	361	(1)
Costs of Medical Care For Diabetic Neuropathy	361	(1)
Costs of Medication	361	(1)
Potential Cost Savings by Prevention of Diabetic Neuropathy	362	(1)
Methodologic Considerations	362	(1)
Costs of Foot Ulcer and Lower-Extremity Amputation	362	(6)
Cost-of-Illness Studies: Data Sources	363	(1)
Center-Based Studies	363	(1)
Databases (Health Insurance Companies)	363	(2)
Hospital-Based Studies	365	(1)
Further Studies on Costs of Diabetic Foot Complications	366	(1)
Economic Modeling: Benefits of Prevention	367	(1)
Cost-Effective Treatment of Diabetic Foot Ulcers	367	(1)
Conclusions	368	(1)
Indirect Consequences: Disability and Premature Death	368	(1)
Socioeconomic Status, Diabetic Neuropathy, and Foot Ulcer	368	(1)
Health-Related Quality of Life and Diabetic Neuropathy	369	(2)
Quality of Life and Peripheral Neuropathy	369	(1)
Quality of Life, Foot Ulcer, and Amputation	370	(1)
Psychological Aspects of Preventive Care	370	(1)
Burden to the Patient	370	(1)
References	371	(2)
Recommendations for Structured Care	373	(5)
F.A. Gries
P.A. Low
D. Ziegler
Introduction	373	(1)
Outpatient Diabetes Care	373	(1)
Screening and Early Detection of Diabetic Neuropathy	374	(1)
Outpatient Care of Diabetic Neuropathy	374	(2)
References	376	(2)
Guidelines for the Diagnosis and Outpatient Management of Diabetic Peripheral Neuropathy	378	(8)
AJM Boulton
F.A. Gries
J.A. Jervell
Definition	378	(1)
Assessment as Part of the Annual Review of the Patient	378	(1)
Management	379	(1)
Appendix 1: International Guide on the Outpatient Management of Diabetic Peripheral Neuropathy	379	(1)
Introduction	379	(2)
Peripheral Neuropathy in Diabetes	380	(1)
Definitions	381	(1)
Stages of Neuropathy	381	(1)
Assessment	381	(1)
Patient History	381	(1)
Examination of the Patient	382	(1)
Other Investigations	382	(1)
The ``At Risk'' Foot	382	(1)
Management	382	(2)
No Clinical Neuropathy (Stage 0/1)	383	(1)
Clinical Neuropathy (Stage 2)	383	(1)
Late Complications of Clinical Neuropathy (Stage 3)	383	(1)
Patient Education	384	(1)
Who Should Provide Patient Education?	384	(1)
What methods should be used?	384	(1)
What elements should the education programme contain?	384	(1)
Summary of the Management of Neuropathy	385	(1)
Acknowledgement	385	(1)
Appendix 2 List of Participants	385	(1)
Pilot Working Party, Brussels, Belgium 13 April 1995	385	(1)
Full Working Party, London, UK, 20-22 October 1995	385	(1)
Index	386