Index. Baroreflex sensitivity, regulation in diabetic autonomic neuropathy, 155, 156 BB/Wor rat

Transcription

1 Index A ACC, see Anterior cingulate cortex ACE inhibitors, see Angiotensin-converting enzyme inhibitors Acupuncture, painful ne uropathy management, 361, 362 Advanced glycation end products (AGEs) diabetic neuropathy pathogenesis, 74 76, 233, 234 inhibitor studies of neuropathy protection, 56, 57, 75, 234, 325 receptor, see Receptor of advanced glycation end product AGEs, see Advanced glycation end products Aldose reductase diabetic neuropathy pathogenesis, function, 34, 52, 53, 72 gene locus and structure, 36 haplotypes and gene expression, 40, 41 inhibitors alrestatin, 310, 312 clinical trials, 233, fidarestat, 318 painful neuropathy management, 357 ponalrestat, 315 prospects for study, 319 sorbinil, tolrestat, zenarestat, 318 zopolrestat, 318 knockout mouse, 55 polyol pathway, 52, 53, 72 promoter polymorphisms A(+11842)C, 40 5 ALR2, C( 106)T, 39, 40 summary of studies, 35, 36 transcriptional activation, 36, 37 transgenic mouse studies global expression, 53, 54 Schwann cell expression, 54 Alprostadil, erectile dysfunction management in diabetes, 467, 468 ALR2, see Aldose reductase Alrestatin, aldose reductase inhibition and clinical trials, 310, 312 Aminoguanidine, diabetic neuropathy management, 325 AMPA receptors, spinal cord studies in diabetes, 179 Anesthesia, cardiovascular autonomic neuropathy risks, 397 Angiotensin-converting enzyme (ACE) inhibitors, neuropathy protection studies, 70 Anhidrosis distal small fiber neuropathy, 427 generalized anhidrosis, 428 multifocal sweating loss, 427, 428 Anterior cingulate cortex (ACC), pain neurocircuitry, 341 Anticonvulsants, painful neuropathy management, 359, 360 Apligraf, foot ulcer management, 493 Apomorphine, erectile dysfunction management in diabetes, 462, 463 Apoptosis autonomic neurons, 123, 124 caspases, 115 cytosolic pathway, 117 dorsal root ganglia, 118, 119, extrinsic pathway, 115 intrinsic pathway, mitochondrial dysfunction, 114 necrosis comparison, 114 oxidative and nitrosative stress in diabetic neuropathy, 117, 118 Schwann cells, 124, 126 spinal cord neurons, 175 Arterial bypass grafting, peripheral arteries, 270 Autonomic neuropathy epidemiology, neuron apoptosis, 123, 124 Axon reflex, neuropathy diagnostics, 284 B Baroreflex sensitivity, regulation in diabetic autonomic neuropathy, 155, 156 BB/Wor rat 507

2 508 Index metabolic abnormalities, myelinated fiber function, structural abnormalities myelinated sensory fibers, 141, 143 nodal and paranodal changes, 143, 144 unmyelinated fiber pathology, 144, 145 structure function correlations myelinated fibers, 145, 146 unmyelinated fibers, 146 type I diabetes polyneuropathy model, 134 unmyelinated fiber function, BBZDR/Wor rat metabolic abnormalities, myelinated fiber function, structural abnormalities myelinated sensory fibers, 141, 143 nodal and paranodal changes, 143, 144 unmyelinated fiber pathology, 144, 145 structure function correlations myelinated fibers, 145, 146 unmyelinated fibers, 146 type II diabetes polyneuropathy model, 134 unmyelinated fiber function, Bcl-2, apoptosis role, 117 Bladder dysfunction diagnosis, 455, 456 management, 456, 457 men, 455 micturition physiology, 454 pathophysiology in diabetes, 454 women, 455 Botulinum toxin, gustatory sweating management, 427 Brainstem auditory evoked potentials, diabetes findings, 196, 197 C CAD, see Coronary artery disease Calcitonin gene-related peptide (CGRP) spinal cord axon studies in diabetes, 173, 179 vasodilation, 209 Calcium flux, oxidative stress and diabetic neuropathy pathogenesis, 82 CAN, see Cardiovascular autonomic neuropathy Capsaicin, painful neuropathy management, 360 Cardiac adrenergic innervation, diabetic autonomic neuropathy, 156, 157 Cardiovascular autonomic neuropathy (CAN) clinical implications anesthesia and surgery risks, 397 cardiac denervation syndrome, exercise performance, 396, 397 orthostatic hypotension, 397 diagnosis cardiovascular autonomic reflex tests, positron emission tomography, 390, 391 scintigraphy, 390, 394, 396 epidemiology, 390, 391 management, natural history, 391, 392 overview, 389, 390 Carpal tunnel syndrome, diabetes association and clinical features, 253, 254, 375 Caspase, apoptosis role, 115 CCM, see Corneal confocal microscopy CGRP, see Calcitonin gene-related peptide Charcot neuroarthropathy clinical findings, 498 etiology, 497, 498 treatment, Chronic inflammatory demyelinating polyradiculopathy (CIDP) clinical features, 252, 263 diabetes association, 22 CIDP, see Chronic inflammatory demyelinating polyradiculopathy Cinitrapide, gastroparesis management in diabetes, 441 Cisapride, gastroparesis management in diabetes, 441 Citalopram, painful neuropathy management, 359 Clinical trial design confounding factors, 288 end points, 287, 288, 309, 310, 322, 323 painful neuropathy, 356 population selection, 287 study duration, 288 Clonidine, gastroparesis management in diabetes, 441, 442 CMAP, see Compound muscle action potential Cognition, see Diabetic encephalopathy Compound muscle action potential (CMAP), neuropathy diagnostics, 282 Constipation clinical findings and evaluation, 445, 446 management, 446

3 Index 509 pathogenesis in diabetes, 445 Corneal confocal microscopy (CCM), neuropathy diagnostics, 285 Coronary artery disease (CAD), diabetes risks, 268, 269 COX-2, see Cyclooxygenase-2 C-peptide, deficiency and diabetic neuropathy, 237 Cranial nerve palsy, diabetic neuropathy clinical manifestations, 368, 369 epidemiology, 368 historical background, 368 management, 376 overview, 253 pathology, 369 Cubitus interruptus, signaling, 94, 95 Cyclooxygenase-2 (COX-2), oxidative stress and diabetic neuropathy pathogenesis, 81 D Debridement, foot ulcer management, Dementia, see Diabetic encephalopathy Dermagraft, foot ulcer management, 492, 493 Diabetic encephalopathy animal studies behavioral findings, 188 hippocampal synaptic plasticity, 188, 189 neurophysiological changes, 189 overview, 187, 188 pathogenetic mechanisms, 189, 190 structural abnormalities, 189 cognition studies clinical management, 198, 199 type 1 diabetes adults, 191 children, 190, 191 type 2 diabetes, dementia studies, 193, 194 depression association, 193, 194 magnetic resonance imaging findings, 194, 196 neuropathological findings, 195 neurophysiology event-related potentials, 197 evoked potentials, 196, 197 therapeutic interventions, 197, 198 Diabetic foot, see Charcot neuroarthropathy; Foot ulcer Diabetic neuropathy animal models, see BB/Wor rat; BBZDR/Wor rat; Streptozotocin-induced diabetes clinical classification, 245, 246 clinical trial design confounding factors, 288 end points, 287, 288, 309, 310, 322, 323 painful neuropathy, 356 population selection, 287 study duration, 288 definition, 351 diagnosis, see Diagnosis, diabetic neuropathy epidemiology, see Epidemiology, diabetic neuropathy genetics, see Genetics, diabetic neuropathy historical perspective see, Historical perspective, diabetic neuropathy types, 8 Diagnosis, diabetic neuropathy axon reflex, 284 cardiovascular autonomic neuropathy, composite scores, 283 corneal confocal microscopy, 285 differential diagnosis, 244, 245, 376 disability assessment, electrophysiology action potentials, 282 F-wave, 282 nerve conduction velocity, magnetic resonance imaging, 285 nerve biopsy, 284 quantitative sensory testing, 279, 280 skin biopsy, see Skin biopsy symptoms, 276, 277 ulceration risk assessment, 279, 280, Diarrhea clinical findings and evaluation, 443, 444 management, 444, 445 pathogenesis in diabetes, 442, 443 Distal symmetrical neuropathy natural history, 249 overview, 246 signs, 246, 247 small fiber neuropathy, 248 symptoms, 246 Domperidone, gastroparesis management in diabetes, 441 Dorsal root ganglia (DRG)

4 510 Index apoptosis in diabetic neuropathy, 118, 119, blood flow, diabetes effects, 118 DRG, see Dorsal root ganglia Duloxetine, painful neuropathy management, 360 Dyslipidemia, diabetic neuropathy pathogenesis, 235, 236 E Encephalopathy, see Diabetic encephalopathy Epalrestat, painful neuropathy management, 357 Epidemiology, diabetic neuropathy amyotrophy and mononeuropathies, autonomic neuropathy frequency and risk, chronic inflammatory demyelinating polyradiculopathy, 22 diabetes type effects, 26 distal symmetric polyneuropathy incidence and risk factors, prevalence and risk factors, 9 13, 243 distal symmetric polyneuropathy incidence and risk factors, prevalence and risk factors, 9 13 foot ulcer, impaired glucose tolerance as risk factor, 26 principles, 8, 9 prospects for study, 26, 27 Erectile dysfunction diabetic autonomic neuropathy studies in animal models, 160, 161 diabetic neuropathy association, 244 diagnosis, 460 epidemiology, 457, 458 management algorithm, 460, 461 alprostadil, 467, 468 apomorphine, 462, 463 penile prosthesis, 468 phentolamine, 466 sildenafil, vacuum devices, 467 vardenafil, 466 yohimbine, 461 physiology and pathophysiology in diabetes, Erythromycin, gastroparesis management in diabetes, 441 Erythropoietin, orthostatic hypotension management, 423, 424 Esophageal dysfunction clinical findings and evaluation, pathogenesis in diabetes, 434 Extracellular signal-regulated kinase, see Mitogen-activated protein kinase F Fecal incontinence clinical findings and evaluation, 446, 447 pathogenesis in diabetes, 446 Female sexual dysfunction (FSD), diabetes association and features, 469 Fidarestat, aldose reductase inhibition and clinical trials, 318 Fludrocortisone, orthostatic hypotension management, 421, 422 Foot ulcer amputation, 474, 475, 497 autonomic and motor neuropathy, 477, 478 classification schemes, 486, 487 clinical examination, economic impact, 473 epidemiology, 474, 475 joint mobility restriction, 479 management debridement, infection treatment, platelet-derived growth factor, 492 pressure offloading, 489 skin substitutes, 492, 493 Wagner grades in treatment guidance grade 0, 494, 495 grade 1, 495, 496 grade 2, 496 grade 3, 496, 497 grade 4, 497 grade 5, 497 wound care, 492 neuropathy as risk factor, pathway, 475, 476 peak plantar pressures, 478, 479 peripheral sensory neuropathy, 476 peripheral vascular disease impaired wound healing, 482, 483 macrocirculation, 479, 480 microcirculation, risk assessment, 279, 280, , risk factors, 474, 475, 483, 484

5 Index 511 FSD, see Female sexual dysfunction F-wave, neuropathy diagnostics, 282 G Gabapentin, painful neuropathy management, 359 Gastroesophageal reflux disease (GERD), features in diabetes, 435 Gastrointestinal symptoms constipation, see Constipation diarrhea, see Diarrhea epidemiology in diabetes, 433 esophageal dysfunction, see Esophageal dysfunction fecal incontinence, see Fecal incontinence gastroparesis syndrome, see Gastroparesis syndrome Gastroparesis syndrome clinical findings and evaluation, management, pathogenesis in diabetes, 436, 437 Genetics, diabetic neuropathy activation abnormalities nerve growth factor, 43 nuclear factor-κb, 41 oxidative stress response genes, 42 poly(adp-ribose) polymerase, 42, 43 protein kinase C, 41 sodium/potassium ATPase, 43 vascular endothelial growth factor, 41 candidate genes aldose reductase, see Aldose reductase identification, 33, 34, 37 mutation types, 33 overview, Genitourinary complications, see Bladder dysfunction; Erectile dysfunction; Female sexual dysfunction GERD, see Gastroesophageal reflux disease Gli, signaling, 94, 95 Glucose counterregulation, hypoglycemia defects, 380, 381, 384 Glutathione, antioxidant activity, 100, 101 Glycemic control, acute painful neuropathy poor glycemic control, 250 rapid glycemic control, 250, 251 Glycemic control neuropathy protection, 69 painful neuropathy management, 356, 357 Gustatory sweating, diabetes association and features, 426, 427 H Hedgehog proteins, see Sonic hedgehog Hippocampus, see Diabetic encephalopathy Historical perspective, diabetic neuropathy ancient period, 1, 2 middle ages, 2 modern era, 4 Western medicine, 3, 4 Hyperglycemia, diabetic neuropathy risks, Hypoglycemia autonomic failure, glucose counterregulation, 380, 381, 384 I IGF-I, see Insulin-like growth factor-i IGT, see Impaired glucose tolerance Impaired glucose tolerance (IGT), diabetic neuropathy risk factor, 26, 231, 232 Incontinence, see Bladder dysfunction; Fecal incontinence Inflammatory demyelinative polyneuropathy, diabetes association and clinical features, 375 Insulin-like growth factor-i (IGF-I) neuroprotection and signaling, 122, 136, 236, 237 therapeutic prospects, 329 Intravenous immunoglobulin (IVIg), clinical trials in diabetic neuropathy, 329 Isosorbide dinitrate, painful neuropathy management, 361 IVIg, see Intravenous immunoglobulin J Jun N-terminal kinase, see Mitogen-activated protein kinase L Laser Doppler flowmetry (LDF) microvascular dysfunction assessment, 266 nerve blood flow, 209, 210, 219, 220 Laser Doppler perfusion imager (LDPI), microvascular dysfunction assessment, LDF, see Laser Doppler flowmetry LDPI, see Laser Doppler perfusion imager Learning and memory, see Diabetic encephalopathy Levitra, see Vardenafil

6 512 Index Lidocaine, painful neuropathy management, 361 γ-linolenic acid, antioxidant therapy in diabetic neuropathy, 325 α-lipoic acid antioxidant therapy in diabetic neuropathy, 324, 325 cardiovascular autonomic neuropathy management, 402, 403 painful neuropathy management, 357 Lipoxygenase, oxidative stress and diabetic neuropathy pathogenesis, 81, 82 Living skin equivalent, foot ulcer management, 492, 493 Loperamide, diarrhea management in diabetes, 444 Lower limb diabetic neuropathy clinical features, 370, 371 electrophysiology, 371 multifocal diabetic neuropathy, 373, 374 pathological aspects, M Magnetic resonance imaging (MRI) brain findings in diabetes, 194, 196 neuropathy diagnostics, 285 MAPK, see Mitogen-activated protein kinase Mcgill pain questionnaire (MPQ), pain assessment, 355 Megalin, sonic hedgehog receptor, 94 Mesenteric arterial function, diabetic autonomic neuropathy, 157 Metatropic glutamate receptors, neuroprotection, 123 Metoclopramide, gastroparesis management in diabetes, 441 Mexiletine, painful neuropathy management, 360 Microangiopathy acute nerve ischemia, blood flow of nerve trunks and dorsal root ganglia, diabetic animal model studies, 213, 215 interventions, 212, 213 nerve regeneration impairment, overview, 207, 208 peripheral nervous system effects in diabetic humans, prospects for study in diabetic neuropathy, resistance to ischemic conduction failure, 215 Microvascular disease anatomic changes, 260, 266 diabetes association, 259, 260 evaluation, pathophysiology in diabetes, 260, 261, Midodrine, orthostatic hypotension management, 420, 421 Mitogen-activated protein kinase (MAPK) activation diabetic neuropathy studies, 102, 103, 105 sensory neurones, 101, 102 apoptosis signaling, 122 extracellular signal-regulated kinases, 97 Jun N-terminal kinases, 98 oxidative stress and diabetic neuropathy pathogenesis, 80 p38 mitogen-activated protein kinases, 98 signaling cascade, 96, 97 stress response, types, 96 MPQ, see Mcgill pain questionnaire MRI, see Magnetic resonance imaging Murcormycosis, diabetes association and clinical features, 375, 376 N NBF, see Nerve blood flow NCV, see Nerve conduction velocity NDF, see Neuropathy Disability Score Nerve biopsy, neuropathy diagnostics, 284 Nerve blood flow (NBF) diabetic neuropathy role, reduction in neuropathy, 70, 71 Nerve conduction velocity (NCV), neuropathy diagnostics, Nerve growth factor (NGF) diabetic neuropathy expression, 238 neuropathy protection, 43 streptozotocin-induced diabetes studies, 160 therapeutic prospects, 329, 330 Neurofilament deficient mouse studies, 59, 60 structure, 59 Neuropathic pain, see Painful neuropathy Neuropathic pain scale, pain assessment, 355 Neuropathy Disability Score (NDS) modified score, 278, 279 overview, 277, 278 Neuropen, foot ulceration risk assessment, 279, 280

7 Index 513 Neurotrophin-3 (NT-3), diabetic neuropathy expression, 238 Neurovascular response, diabetics, NF-κB, see Nuclear factor-κb NGF, see Nerve growth factor NHE-1, see Sodium/proton exchanger-1 Nitric oxide synthase (NOS) diabetic nerve response, 217 endothelial dysfunction in diabetes, 261 erectile dysfunction pathophysiology, 459, 460 Nitrosative stress apoptosis in diabetic neuropathy, 117, 118 diabetic neuropathy pathogenesis, 42, 76 78, 100 NMDA receptors, spinal cord studies in diabetes, 179 NOS, see Nitric oxide synthase NT-3, see Neurotrophin-3 Nuclear factor-κb (NF-κB) diabetes activation, 41, 232 oxidative stress and diabetic neuropathy pathogenesis, 80, 81 reporter studies in transgenic mice, 61 O Octreotide, diarrhea management in diabetes, 444, 445 Opioids, painful neuropathy management, 360 Orthostatic hypotension blood pressure regulation, 414, 415 cardiovascular autonomic neuropathy, 397 clinical manifestations, 416, 418 definition, 413, 414 laboratory evaluation, 418, 419 management early morning orthostatic hypotension, 423 erythropoietin, 423, 424 fludrocortisone, 421, 422 hospital management, 422, 423 midodrine, 420, 421 nocturnal hypertension, 423 orthostatic decompensation, 421, 422 patient education, 419, 420 postprandial orthostatic hypotension, 423 pyridostigmine, 421 pathophysiology in diabetes, 415, 416 symptom severity scale, 417 Oxidative stress apoptosis in diabetic neuropathy, 117, 118 cardiovascular autonomic neuropathy, 402, 403 diabetic neuropathy pathogenesis, 42, 76 78, 234, 235 downstream effectors calcium flux, 82 cyclooxygenase-2, 81 lipoxygenase, 81, 82 mitogen-activated protein kinases, 80, nuclear factor-κb, 80, 81 poly(adp-ribose) polymerase, sodium/proton exchanger-1, 82, 83 P p38 mitogen-activated protein kinase, see Mitogen-activated protein kinase P100, diabetes findings, 196, 197 P300, diabetes findings, 197 Painful neuropathy acute painful neuropathy poor glycemic control, 250 rapid glycemic control, 250, 251 animal models, 345, 346 brain changes acute pain responses, chronic pain responses, 342, 344, 345 overview, 340 chronic sensorimotor neuropathy, 353, 354 clinical trial design, 356 focal and multifocal neuropathies, 352, 353 general symmetrical polyneuropathy, 353 overview, 249, 250 pain assessment, 354, 355 quality of life, 355 treatment acupuncture, 361, 362 aldose reductase inhibitors, 357 anticonvulsants, 359, 360 duloxetine, 360 glycemic control, 356, 357 α-lipoic acid, 357 mexiletine, 360 opioids, 360 phototherapy, 362 protein kinase C inhibitors, 357, 358 psychological support, 361 selective serotonin reuptake inhibitors, 359 topical therapy, 360, 361 tricyclic antidepressants, 358, 359 Paroxetine, painful neuropathy management, 359 PARP, see Poly(ADP-ribose) polymerase

8 514 Index Patched, hedgehog protein receptor, 94 PDGF, see Platelet-derived growth factor Percutaneous transluminal angioplasty, peripheral arteries, 270 Peripheral vascular disease diabetes risks, 269, 270 diabetic foot impaired wound healing, 482, 483 macrocirculation, 479, 480 microcirculation, Peroneal nerve, entrapment, 254 Phentolamine, erectile dysfunction management in diabetes, 466 Phototherapy, painful neuropathy management, 362 PKC, see Protein kinase C Platelet-derived growth factor (PDGF), foot ulcer management, 492 Poly(ADP-ribose) polymerase (PARP) apoptosis role, 114 diabetes activation, 42, 43, 58 DNA repair, 121 inhibitor studies of neuropathy protection, 59 knockout mouse, 58, 59 oxidative stress and diabetic neuropathy pathogenesis, Polyol pathway, see Aldose reductase; Sorbitol dehydrogenase Ponalrestat, aldose reductase inhibition and clinical trials, 315 Pregabalin, painful neuropathy management, 359, 360 Programmed cell death, see Apoptosis Protein kinase C (PKC) aldose reductase transgenic mouse and reduced activation, 53, 54 diabetes activation, 41, 76 diabetic neuropathy pathogenesis, 235 inhibitor therapy, 326, 327, 357, 358 knockout mouse, 52 Proximal motor neuropathy, clinical features, 251, 252 Punch biopsy, see Skin biopsy Pyridostigmine, orthostatic hypotension management, 421 Q QoL, see Quality of life QSART, see Quantitative Sudomotor Axon Reflex Test QST, see Quantitative sensory testing Quality of life (QoL), painful neuropathy, 355 Quantitative sensory testing (QST), neuropathy, 279, 280 Quantitative Sudomotor Axon Reflex Test (QSART), sudomotor failure evaluation, 424, 425 R RAGE, see Receptor of advanced glycation end product Reactive oxygen species, see Oxidative stress Receptor of advanced glycation end product (RAGE) knockout mouse, 57, 58, 60 nuclear factor-κb activation, 41, 57 signaling, 101 Resistance to ischemic conduction failure (RICF), axons, 215 Retinal, ischemia response, 71 RICF, see Resistance to ischemic conduction failure Ruboxistaurin mesylate clinical trials in diabetic neuropathy, 326, 327 painful neuropathy management, 357 S Schwann cell, apoptosis in diabetic neuropathy, 124, 126 SDH, see Sorbitol dehydrogenase SDI-58, streptozotocin-induced diabetes studies, 160 Secromotor function, diabetic autonomic neuropathy findings, 158, 159 Selective serotonin reuptake inhibitors, painful neuropathy management, 359 Semmes-Weinstein monofilament test, diabetic foot evaluation, 485 Sensory nerve action potential (SNAP), neuropathy diagnostics, 282 Shh, see Sonic hedgehog Sildenafil erectile dysfunction management in diabetes, gastroparesis management in diabetes, 442 Skin biopsy, neuropathy diagnostics blister formation biopsy, 296 epidermal innervation in clinical trials,

9 Index 515 epidermal nerve and sural nerve correlation, 298, 300, 301 overview, 284, 293, 294 processing and analysis, punch biopsy, 296 site selection, Small fiber neuropathy, features, 248 SNAP, see Sensory nerve action potential Sodium/potassium ATPase diabetes activation, 43 rat polyneuropathy model activity, 135 Sodium/proton exchanger-1 (NHE-1), oxidative stress and diabetic neuropathy pathogenesis, 82, 83 Somatic nerve fibers, vasoregulation in diabetic autonomic neuropathy, 154 Somatosensory evoked potentials, diabetes findings, 197 Sonic hedgehog (Shh) hedgehog proteins and functions, immunocomplex therapy effects on diabetic neuropathy indices, 95, 96 receptors and signaling, 94, 95 Sorbinil, aldose reductase inhibition and clinical trials, Sorbitol dehydrogenase (SDH) function, 52 inhibitor treatment in streptozotocin-induced diabetes, 160 knockout mouse, 55, 56 Spinal cord diabetic neuropathology animal models, apoptosis, 175 humans, electrophysiology studies in diabetes conduction velocity, 176, 177 response properties, 177 functional anatomy, gray matter, 169, 170 neurochemistry in diabetes neurotransmitter receptors, neurotransmitter release, 177, 178 pharmacology, 179, 181 white matter ascending tracts, 170, 171 descending tracts, 171, 172 Splanchic-mesenteric bed, diabetic autonomic neuropathy findings, 157, 158 SSR, see Sympathetic skin response Statins, diabetic neuropathy benefits, 235, 236 Streptozotocin-induced diabetes autonomic ganglia function, 159, 160 cardiac adrenergic innervation, 156, 157 cardiovagal function, 155, 156 diabetic encephalopathy studies behavioral findings, 188 hippocampal synaptic plasticity, 188, 189 neurophysiological changes, 189 overview, 187, 188 pathogenetic mechanisms, 189, 190 structural abnormalities, 189 secromotor function, 158, 159 spinal cord neuropathology, splanchic-mesenteric bed findings, 157, 158 Sudomotor disorders evaluation Quantitative Sudomotor Axon Reflex Test, 424, 425 sympathetic skin response, 424, 425 thermoregulatory sweat test, 425 symptoms, 424 Sympathetic skin response (SSR), sudomotor failure evaluation, 424, 425 T Thermoregulatory sweat test (TST), sudomotor failure evaluation, 425 Tolrestat, aldose reductase inhibition and clinical trials, Topiramate, clinical trials in diabetic neuropathy, 330, 331 Toronto clinical neuropathy scoring system, 279 Tricyclic antidepressants, painful neuropathy management, 358, 359 Truncal neuropathy, features, 375 Truncal radiculopathy, clinical features, 253 TST, see Thermoregulatory sweat test U Ulnar nerve, entrapment, 254 Upper limb diabetic neuropathy, focal neuropathy, 375 Urinary incontinence, see Bladder dysfunction V Vacuum devices, erectile dysfunction management in diabetes, 467 Vardenafil, erectile dysfunction management in diabetes, 466

10 516 Index VAS, see Visual analog scale Vascular endothelial growth factor (VEGF) diabetic neuropathy pathogenesis, 41, 237, 238 therapeutic prospects, 327 Vasomax, see Phentolamine VEGF, see Vascular endothelial growth factor Viagra, see Sildenafil Vibration pressure threshold (VPT), foot ulcer risk assessment, 486 Visual analog scale (VAS), pain assessment, 354, 355 Vitamin E, antioxidant therapy in diabetic neuropathy, 325 VPT, see Vibration pressure threshold W Wound healing, diabetic foot, 482, 483 Y Yohimbine, erectile dysfunction management in diabetes, 461 Z Zenarestat, aldose reductase inhibition and clinical trials, 318 Zopolrestat, aldose reductase inhibition and clinical trials, 318a