Metabolic Alterations in Experimental Models
A.A.F. Sima and C.R. Pierson
Introduction
The Polyol Pathway and the Na+, K+-ATPase Defect
Role of Nonenzymatic Glycation
Role of Oxidative Stress and Alterations in Blood Flow
Role of Essential Fatty Acids
Role of Neurotrophic Factors
Neuropathy Associated with Hyperinsulinemia and Hypoglycemia
Physiologic Role of Proinsulin C-Peptide
Relationships Between Metabolic Alterations and Structural Pathology in Type 1 and Type 2 Diabetic Neuropathy
Future Directions
Summary
Glycation and Advanced Glycation Reactions
J. W. Baynes
Introduction
Maillard Reaction Products
Diabetic Neuropathy
Conclusions
Polyolpathway: Aldose Reductase Inhibitors—Hope for the Future?
E.L. Feldman. K.A. Sullivan, and M.J. Stevens
Introduction
Pathophysiology
Therapy
Summary
Nerve Blood Flow
M.A. Cotter. A. Veves. S. Tesfaye, and N.E. Cameron
Introduction
Nerve Blood Flow in Diabetic Patients
Nerve Axon Reflex
Blood Vessel Morphology in Diabetic Nerves
Treatments to Test the Vascular Hypothesis in Peripheral Diabetic Neuropathy
Importance of Neuron Cell Bodies
Oxidative Stress: An Integrative View
P.A. Low
Introduction
Presence of Oxidative Stress in Human and Experimental Diabetes
Free Radical Defenses Are Reduced in Peripheral Nerve
Reduced Oxygen Species Are Increased In Experimental Diabetic Neuropathy
Changes in Pro-oxidant Status
Neural Targets of Oxidant Stress
Synthesis of Pathogenetic Hypothesis
Concluding Thoughts
Neurotrophic Factors
A. Vinik, C. Pittenger, K. Stansberry, T.S. Park, T. Erbas. and M. Skeen
Introduction
Insulin and IGFs as Neurotrophic Factors
Neuroimmunophilins
Programmed Cell Death and Neuropathy
Glutamate Neurotoxicity and Its Prevention
NAAGS in Diabetic Neuropathy
Therapeutic Potential for Growth Factors
Caveats on the Use of Neurotrophic Factors in the Clinic
Autoimmunity
P.J. Watkins and G. Sundkvist
Introduction
Autoimmunity and the Nervous System
Conclusions
References
5 Clinical Features and Treatment of Diabetic Neuropathy
Severity and Staging of Diabetic Polyneuropathy
P.J. Dyck
Why Quantitate the Severity of Diabetic Polyneuropathy?
How Is Severity of Diabetic Polyneuropathy to Be Judged?
Minimum Criteria for the Diagnosis of Diabetic Neuropathy
Can Neuropathic Abnormalities Be Demonstrated in Patients Who Do not Fulfill Minimum Criteria for Diabetic Polyneuropathy?
Severity of Neuropathic Symptoms
Continuous Measures of Neuropathic Impairment
Composite Scores for Diabetic Polyneuropathy Severity
Staging Severity of Diabetic Polyneuropathy
Classification of the Diabetic Neuropathies
P.K. Thomas
Hyperglycemic Neuropathy
Diabetic Distal Sensory or Sensorimotor Polyneuropathy
Acute Painful Diabetic Neuropathy
Autonomic Neuropathy
Acute Motor Neuropathy
Focal and Multifocal Neuropathies
Cranial Neuropathies
Thoracolumbar Radiculoneuropathy
Proximal Diabetic Neuropathy
Focal Limb Nerve Lesions
Superimposed Chronic Inflammatory Demyelinating Polyneuropathy
Hypoglycemic Neuropathy
Diabetic Sensorimotor Neuropathy: Methods of Assessment
Electrophysiologic Testing
V. Bril
Introduction to Electrophysiology
Nerve Conduction Studies in Neuropathies: An Overview
Axonal Neuropathies: Diabetic Neuropathy as the Prototype
Methodology
Limitations
Summary
Quantitative Sensory Testing
J.C. Arezzo
Introduction
Pathophysiology Underlying the Elevation of Sensory Thresholds
Methodology
Vibration Perception Threshold
Thermal Perception Threshold
Simple Devices
Epidemiologic Studies and Multicenter Clinical Trials
Limitations of QST in the Assessment of Diabetic Neuropathy