Skip to main content
Top

10-04-2012 | Diabetic foot ulcers | Book chapter | Article

3. Diabetic Polyneuropathy

Author: Solomon Tesfaye, MD, FRCP

Publisher: Humana Press

Abstract

Diabetic neuropathy is a common complication of diabetes and a cause of considerable morbidity and increased mortality. Diabetic neuropathy is not a single entity but encompasses several neuropathic syndrome. However, by far, the commonest presentation of neuropathy in diabetes is chronic distal symmetrical polyneuropathy also commonly known as diabetic peripheral neuropathy (DPN). The Toronto Diabetic Neuropathy Consensus Panel defined DPN as “a symmetrical, length-dependent sensorimotor polyneuropathy attributable to metabolic and microvessel alterations as a result of chronic hyperglycemia exposure and cardiovascular risk covariates. An abnormality of nerve conduction (NC) tests, which is frequently subclinical, appears to be the first objective quantitative indication of the condition. The occurrences of diabetic retinopathy and nephropathy in a given patient strengthen the case that the polyneuropathy is attributable to diabetes”. This chapter covers all the neuropathic syndromes encountered in diabetes mellitus, although the main focuses are (1) DPN, which is the main initiating factor for foot ulceration and a cause of troublesome chronic painful neuropathic symptoms, and (2) autonomic neuropathy, often associated with DPN that can involve almost all the systems of the body and may have devastating consequences, such as sudden death.
Literature
1.
Tesfaye S, Boulton AJM, Dyck PJ, et al. Diabetic neuropathies: update on definitions, diagnostic criteria, estimation of severity and treatments. Diabetes Care. 2010;33:2285–93.PubMed
2.
Dyck PJ, Kratz KM, Karnes JL, Litchy WJ, Klein R, Pach JM, Wilson DM, O’Brien PC, Melton LJ. The prevalence by staged severity of various types of diabetic neuropathy, retinopathy, and nephropathy in a population-based cohort: the Rochester Diabetic Neuropathy Study. Neurology. 1993;43:817–24.PubMed
3.
Shaw JE, Zimmet PZ. The epidemiology of diabetic neuropathy. Diabetes Rev. 1999;7:245–52.
4.
Tesfaye S, Stephens L, Stephenson J, Fuller J, Platter ME, Ionescu-Tirgoviste C, Ward JD. The prevalence of diabetic neuropathy and its relation to glycaemic control and potential risk factors: the EURODIAB IDDM Complications Study. Diabetologia. 1996;39:1377–84.PubMed
5.
Tesfaye S, Chaturvedi N, Eaton SEM, Witte D, Ward JD, Fuller J. Vascular risk factors and diabetic neuropathy. N Engl J Med. 2005;352:341–50.PubMed
6.
Andreassen CS, Jakobsen J, Ringgaard S, Ejskjaer N, Andersen H. Accelerated atrophy of lower leg and foot muscles—a follow-up study of long-term diabetic polyneuropathy using magnetic resonance imaging (MRI). Diabetologia. 2009;52(6):1182–91.PubMed
7.
Watkins PJ. Pain and diabetic neuropathy. Br Med J. 1984;288:168–9.
8.
Tesfaye S, Price D. Therapeutic approaches in diabetic neuropathy and neuropathic pain. In: Boulton AJM, editor. Diabetic neuropathy. Camforth: Marius; 1997. p. 159–81.
9.
Quattrini C, Tesfaye S. Understanding the impact of painful diabetic neuropathy. Diabetes Metab Res Rev. 2003;19 Suppl 1:S1–8.
10.
Ewing DJ, Martyn CN, Young RJ, Clarke BF. The value of cardiovascular autonomic function tests: ten years experience in diabetes. Diabetes Care. 1985;8:491–8.PubMed
11.
Boulton AJ, Kirsner RS, Vileikyte Vileikyte. Clinical practice. Neuropathic diabetic foot ulcers. N Engl J Med. 2004;351(1):48–55.PubMed
12.
Ward JD. The diabetic leg. Diabetologia. 1982;22:141–7.PubMed
13.
Tesfaye S. Diabetic neuropathy: achieving best practice. Br J Vasc Dis. 2003;3:112–7.
14.
Rajbhandari SM, Jenkins R, Davies C, Tesfaye S. Charcot neuroarthropathy in diabetes mellitus. Diabetologia. 2002;45(8):1085–96.PubMed
15.
Ward JD, Simms JM, Knight G, Boulton AJM, Sandler DA. Venous distension in the diabetic neuropathic foot (physical sign of arterio-venous shunting). J Roy Soc Med. 1983;76:1011–4.PubMed
16.
Boulton AJM, Scarpello JHB, Ward JD. Venous oxygenation in the diabetic neuropathic foot: evidence of arterial venous shunting? Diabetologia. 1982;22:6–8.PubMed
17.
Edmonds ME, Archer AG, Watkins PJ. Ephedrine: a new treatment for diabetic neuropathic oedema. Lancet. 1983;1:548–51.PubMed
18.
Young MJ, Boulton AJ, MacLeod AF, Williams DR, Sonksen PH. A multicentre study of the prevalence of diabetic peripheral neuropathy in the United Kingdom hospital clinic population. Diabetologia. 1993;36(2):150–4.PubMed
19.
Bril V, Perkins BA. Validation of the Toronto Clinical Scoring System for diabetic polyneuropathy. Diabetes Care. 2002;25(11):2048–52.PubMed
20.
Feldman EL, Stevens MJ, Thomas PK, Brown MB, Canal N, Greene DA. A practical two-step quantitative clinical and electrophysiological assessment for the diagnosis and staging of diabetic neuropathy. Diabetes Care. 1994;17(11):1281–9.PubMed
21.
Dyck PJ. Detection, characterization, and staging of polyneuropathy: assessed in diabetics. Muscle Nerve. 1988;11:21–32.PubMed
22.
Ad hoc panel on endpoints for diabetic neuropathy trials. Positive neuropathic sensory symptoms as endpoints in diabetic neuropathy trials. J Neurol Sci. 2001;189:3–6.
23.
Dyck PJ, Overland CJ, Low PA, Litchy WJ, Davies JL, Dyck PJB, O’Brien PC, Andersen H, Albers JW, Bolton CF, England J, Klein CJ, Llewelyn G, Mauermann ML, Russell JW, Singer W, Smith G, Tesfaye S, Vella A. Signs and symptoms vs nerve conduction studies to diagnose diabetic sensorimotor polyneuropathy. Muscle Nerve. 2010;42(2):157–64.PubMed
24.
Archer AG, Watkins PJ, Thomas PJ, Sharma AK, Payan J. The natural history of acute painful neuropathy in diabetes mellitus. J Nurol Neorosurg Psychiatry. 1983;46:491–6.
25.
Ellenberg M. Diabetic neuropathic cachexia. Diabetes. 1974;23:418–23.PubMed
26.
Devigili G, Tugnoli V, Penza P, Camozzi F, Lombardi R, Melli G, Broglio L, Granieri E, Lauria G. The diagnostic criteria for small fibre neuropathy: from symptoms to neuropathology. Brain. 2008;131(Pt 7):1912–25.PubMed
27.
Tesfaye S, Malik R, Harris N, Jakubowski J, Mody C, Rennie IG, Ward JD. Arteriovenous shunting and proliferating new vessels in acute painful neuropathy of rapid glycaemic control (insulin neuritis). Diabetologia. 1996;39:329–35.PubMed
28.
Said G, Slama G, Selva J. Progressive centripital degeneration of axons in small-fibre type diabetic polyneuropathy. A clinical and pathological study. Brain. 1983;106:791.PubMed
29.
Vinik AI, Park TS, Stansberry KB, Pittenger GL. Diabetic neuropathies. Diabetologia. 2000;43:957–73.PubMed
30.
Singleton JR, Smith AG, Bromberg MB. Increased prevalence of impaired glucose tolerance in patients with painful sensory neuropathy. Diabetes Care. 2001;24(8):1448–53.PubMed
31.
Veves A, Young MJ, Manes C, et al. Differences in peripheral and autonomic nerve function measurements in painful and painless neuropathy: a clinical study. Diabetes Care. 1994;17:1200–2.PubMed
32.
Kennedy WR, Wendelschafer-Crabb G, Johnson T. Quantitation of epidermal nerves in diabetic neuropathy. Neurology. 1996;47(4):1042–8.PubMed
33.
Ebenezer GJ, Hauer P, Gibbons C, McArthur JC, Polydefkis M. Assessment of epidermal nerve fibers: a new diagnostic and predictive tool for peripheral neuropathies. J Neuropathol Exp Neurol. 2007;66(12):1059–73.PubMed
34.
Matikainen E, Juntunen J. Diabetic neuropathy: epidemiological, pathogenetic, and clinical aspects with special emphasis on type 2 diabetes mellitus. Acta Endocrinol Suppl (Copenh). 1984;262:89–94.
35.
Garland H. Diabetic amyotrophy. Br Med J. 1955;2:1287–90.PubMed
36.
Coppack SW, Watkins PJ. The natural history of femoral neuropathy. Q J Med. 1991;79:307–13.PubMed
37.
Casey EB, Harrison MJG. Diabetic amyotrophy: a follow-up study. Br Med J. 1972;1:656.PubMed
38.
Bastron JA, Thomas JE. Diabetic polyradiculoneuropathy: clinical and electromyographic findings in 105 patients. Mayo Clin Proc. 1981;56:725–32.PubMed
39.
Said G, Goulon-Goeau C, Lacroix C, Moulonguet A. Nerve biopsy findings in different patterns of proximal diabetic neuropathy. Ann Neurol. 1994;33:559–69.
40.
Asbury AK, Aldredge H, Hershberg R, Fisher CM. Oculomotor palsy in diabetes mellitus: a clinicopathological study. Brain. 1970;93:555–7.PubMed
41.
Zorilla E, Kozak GP. Ophthalmoplegia in diabetes mellitus. Ann Intern Med. 1967;67:968–76.
42.
Goldstein JE, Cogan DG. Diabetic ophthalmoplegia with special reference to the pupil. Arch Ophthalmol. 1960;64:592–600.PubMed
43.
Leslie RDG, Ellis C. Clinical course following diabetic ocular palsy. Postgrad Med J. 1978;54:791–2.
44.
Dreyfuss PM, Hakim S, Adams RD. Diabetic ophthalmoplegia. Arch Neurol Psychiatry. 1957;77:337–49.
45.
Ellenberg M. Diabetic truncal mononeuropathy—a new clincal syndrome. Diabetes Care. 1978;1:10–3.PubMed
46.
Boulton AJM, Angus E, Ayyar DR, Weiss R. Diabetic thoracic polyradiculopathy presenting as abdominal swelling. BMJ. 1984;289:798–9.PubMed
47.
Obrosova IG. Diabetic painful and insensate neuropathy: pathogenesis and potential treatments. Neurotherapeutics. 2009;6(4):638–47.PubMed
48.
Malik RA, Newrick PG, Sharma AK, Jennings A, Ah-See AK, Mayhew TM, Jakubowski J, Boulton AJM, Ward JD. Microangiopathy in human diabetic neuropathy: relationship between capillary abnormalities and the severity of neuropathy. Diabetologia. 1989;32:92–102.PubMed
49.
Bradley JL, Thomas PK, King RH, Muddle JR, Ward JD, Tesfaye S, Boulton AJM, Tsigos C, Young RJ. Myelinated nerve fibre regeneration in diabetic sensory polyneuropathy: correlation with type of diabetes. Acta Neuropathol. 1995;90:403–10.PubMed
50.
Cameron NE, Eaton SE, Cotter MA, Tesfaye S. Vascular factors and metabolic interactions in the pathogenesis of diabetic neuropathy. Diabetologia. 2001;44:1973–88.PubMed
51.
Pacher P, Obrosova IG, Mabley JG, Szabó C. Role of nitrosative stress and peroxynitrite in the pathogenesis of diabetic complications. Emerging new therapeutical strategies. Curr Med Chem. 2005;12(3):267–75.PubMed
52.
Figueroa-Romero C, Sadidi M, Feldman EL. Mechanisms of disease: the oxidative stress theory of diabetic neuropathy. Rev Endocr Metab Disord. 2008;9(4):301–14.PubMed
53.
Szabo C. Role of nitrosative stress in the pathogenesis of diabetic vascular dysfunction. Br J Pharmacol. 2009;156(5):713–27.PubMed
54.
Obrosova IG, Drel VR, Pacher P, Ilnytska O, Wang ZQ, Stevens MJ, Yorek MA. Oxidative-nitrosative stress and poly(ADP-ribose) polymerase (PARP) activation in experimental diabetic neuropathy: the relation is revisited. Diabetes. 2005;54(12):3435–41.PubMed
55.
Giannini C, Dyck PJ. Ultrastructural morphometric abnormalities of sural nerve endoneurial microvessels in diabetes mellitus. Ann Neurol. 1994;36:408–15.PubMed
56.
Malik RA, Tesfaye S, Thompson SD, Veves A, Boulton AJM, Ward JD. Endoneurial localisation of microvascular damage in human diabetic neuropathy. Diabetologia. 1993;36:454–9.PubMed
57.
Tesfaye S, Harris N, Jakubowski J, et al. Impaired blood flow and arterio-venous shunting in human diabetic neuropathy: a novel technique of nerve photography and fluorescein angiography. Diabetologia. 1993;36:1266–74.PubMed
58.
Newrick PG, Wilson AJ, Jakubowski J, Boulton AJM, Ward JD. Sural nerve oxygen tension in diabetes. Br Med J. 1986;193:1053–4.
59.
Tesfaye S, Harris N, Wilson RM, Ward JD. Exercise induced conduction velocity increment: a marker of impaired blood flow in diabetic neuropathy. Diabetologia. 1992;35:155–9.PubMed
60.
Young MJ, Veves A, Smith JV, Walker MG, Boulton AJM. Restoring lower limb blood flow improves conduction velocity in diabetic patients. Diabetologia. 1995;38:1051–4.PubMed
61.
Reja A, Tesfaye S, Harris ND, Ward JD. Is ACE inhibition with lisinopril helpful in diabetic neuropathy? Diabetic Med. 1995;12:307–9.PubMed
62.
Malik RA, Williamson S, Abbott CA, Carrington AL, Iqbal J, Schady W, Boulton AJM. Effect of the angiotensin converting enzyme inhibitor trandalopril on human diabetic neuropathy: a randomised controlled trial. Lancet. 1998;352:1978–81.PubMed
63.
Pfeifer MA, Weinberg CR, Cook DL, et al. Autonomic neural dysfunction in recently diagnosed diabetic subjects. Diabetes Care. 1984;7:447–53.PubMed
64.
Witte DR, Tesfaye S, Chaturvedi N, Eaton SEM, Kempler P, Fuller JH, and the EURODIAB Prospective Complications Study Group. Risk factors for cardiac autonomic neuropathy in Type 1 diabetes mellitus. Diabetologia. 2005;48:164–71.PubMed
65.
Diabetes Control and Complications Trial Research Group. The effect of intensive diabetes therapy on the development and progression of neuropathy. Ann Intern Med. 1995;122:561–8.
66.
Spallone V, Ziegler D, Freeman R, Bernardi L, Frontoni S, Pop-Busui R, Stevens M, Kempler P, Hilsted J, Tesfaye S, Low P, Valensi P; on behalf of the Toronto Consensus Panel on Diabetic Neuropathy*. Cardiovascular autonomic neuropathy in diabetes: clinical impact, assessment, diagnosis, and management. Diabetes Metab Res Rev. 2011; doi: 10.​1002/​dmrr.​1239.
67.
Vinik AI, Ziegler D. Diabetic cardiovascular autonomic neuropathy. Circulation. 2007;115:387–97.PubMed
68.
Gæde P, Vedel P, Larsen N, et al. Multifactorial intervention and cardiovascular disease in patients with type 2 diabetes. N Engl J Med. 2003;348:383–93.PubMed
69.
Purewal TS, Goss DE, Watkins PJ, Edmonds ME. Lower limb venous pressure in diabetic neuropathy. Diabetes Care. 1995;18:377–81.PubMed
70.
The Consensus Committee of the American Autonomic Society and the American Academy of Neurology. Consensus statement on the definition of orthostatic hypotension, pure autonomic failure, and multiple system atrophy. Neurology. 1996;46:1470.
71.
MacLean AR, Allen BV. Orthostatic hypotension and orthostatic tachycardia: treatment with the “head-up” bed. JAMA. 1940;115:2162–7.
72.
Lu CC, Diedrich A, Tung CS, et al. Water ingestion as prophylaxis against syncope. Circulation. 2003;108:2660–5.PubMed
73.
Low PA, Gilden JL, Freeman R, et al. Efficacy of midodrine vs placebo in neurogenic orthostatic hypotension. A randomized, double-blind multicenter study. Midodrine Study Group. JAMA. 1997;277:1046–51.PubMed
74.
Ghrist DG, Brown GE. Postural hypotension with syncope: its successful treatment with ephedrine. Am J Med Sci. 1928;175:336–49.
75.
Heoldtke RD. Treatment of autonomic neuropathy, postural tachycardia and orthostatic syncope with octreotide LAR. Clin Auton Res. 2007;17:334–440.
76.
Hoeldtke RD, Streeten DHP, Streeten DH. Treatment of orthostatic hypotension with erythropoietin. N Engl J Med. 1993;329:611–5.PubMed
77.
Horowitz M, Fraser R. Disordered gastric motor function in diabetes mellitus. Diabetologia. 1994;37:543–51.PubMed
78.
Lacy BE, Crowell MD, Schettler-Duncan A, et al. The treatment of diabetic gastroparesis with botulinum toxin injection of the pylorus. Diabetes Care. 2004;27:2341–7.PubMed
79.
Friedenberg FK, Palit A, Parkman HP, et al. Botulinum toxin A for the treatment of delayed gastric emptying. Am J Gastroenterol. 2008;103:416–23.PubMed
80.
Abell T, McCallum R, Hocking M, et al. Gastric electrical stimulation for medically refractory gastroparesis. Gastroenterology. 2003;125:421–8.PubMed
81.
Lin Z, Forster J, Sarosiek I, McCallum RW. Treatment of diabetic gastroparesis by high-­frequency gastric electrical stimulation. Diabetes Care. 2004;27:1071–6.PubMed
82.
Sheehy TW. Diabetic gustatory sweating. Am J Gastroenterol. 1991;86:1514–7.PubMed
83.
Atkin SL, Brown PM. Treatment of gustatory sweating with topical glycopyrrolate cream. Diabetic Med. 1996;13:493–4.PubMed
84.
Shaw JE, Abbott CA, Tindle K, et al. A randomized, controlled trial of topical glycopyrrolate, the first specific treatment for diabetic gustatory sweating. Diabetologia. 1997;40:299–301.PubMed
85.
Naumann M. Evidence-based medicine: botulinum toxin in focal hyperhidrosis. J Neurology. 2001;248 Suppl 1:31–3.
86.
Treede R-D, Jensen TS, Campbell JN, et al. Neuropathic pain: redefinition and a grading system for clinical and research purposes. Neurology. 2008;70:1630–5.PubMed
87.
Zelman DC, Brandenburg NA, Gore M. Sleep impairment in patients with painful diabetic peripheral neuropathy. Clin J Pain. 2006;22:681–5.PubMed
88.
Gore M, Brandenburg NA, Dukes E, et al. Pain severity in diabetic peripheral neuropathy is associated with patient functioning, symptom levels of anxiety and depression, and sleep. J Pain Symptom Manage. 2005;30:374–85.PubMed
89.
Vileikyte L, Leventhal H, Gonzalez J, et al. Diabetic peripheral neuropathy and depressive symptoms: the association revisited. Diabetes Care. 2005;28:2378–83.PubMed
90.
Vileikyte L, Peyrot M, Gonzalez JS, et al. Predictors of depressive symptoms in persons with diabetic peripheral neuropathy: a longitudinal study. Diabetologia. 2009;52:1265–73.PubMed
91.
Sankar A, Selvarajah D, Gandhi R, Oleolo M, Emery C, Tesfaye S. Significant impact of mood disturbances of pain perception in painful DPN: time to re-evaluate current practice? Diabetologia. 2010;53 Suppl 1:S446.
92.
Tesfaye S, Boulton AJM, editors. Diabetic neuropathy. Oxford: Oxford University Press. 2009.
93.
Davies M, Brophy S, Williams R, Taylor A. The prevalence, severity, and impact of painful diabetic peripheral neuropathy in type 2 diabetes. Diabetes Care. 2006;29(7):1518–22.PubMed
94.
Daousi C, McFarlane IA, Woodward A, Nurmikko TJ, Bendred PE, Benbow SJ. Chronic painful peripheral neuropathy in an urban community: a control comparison of people with and without diabetes. Diabet Med. 2004;21:976–82.PubMed
95.
Tesfaye S, Kempler P. Painful diabetic neuropathy. Diabetologia. 2005;48:805–7.PubMed
96.
Oyibo SO, Prasad YDM, Jackson NJ, Boulton AJM. The relationship between blood glucose excursions and painful diabetic peripheral neuropathy: a pilot study. Diabet Med. 2002;19:870–3.PubMed
97.
Eaton SE, Harris ND, Ibrahim S, Patel K, Selmi F, Radatz M, Ward JD, Tesfaye S. Differences insural nerve haemodynamics in painful and painless neuropathy. Diabetologia. 2003;46:934–9.PubMed
98.
Quattrini C, Harris ND, Malik RA, Tesfaye S. Impaired skin microvascular reactivity in painful diabetic neuropathy. Diabetes Care. 2007;30:655–9.PubMed
99.
Sorensen L, Molyneaux L, Yue DK. The relationship among pain, sensory loss, and small nerve fibers in diabetes. Diabetes Care. 2006;29:883–7.PubMed
100.
Selvarajah D, Wilkinson ID, Gandhi R, Emery CJ, Griffiths PD, Tesfaye S. Unique thalamic micerovascular perfusion abnormalities in painful but not painless diabetic polyneuropathy; a clue to the pathogenesis of pain in type1 diabetes mellitus. Diabetes Care. 2011;34(3):718–20.PubMed
101.
Gandhi R, Marques JLB, Selvarajah D, et al. Painful diabetic neuropathy is associated with greater autonomic dysfunction than painless diabetic neuropathy. Diabetes Care. 2010;33:1585–90.PubMed
102.
Cruccu G, Sommer C, Anand P, Attal N, Baron R, Garcia-Larrea L, Haanpaa M, Jensen TS, Serra J, Treede RD. EFNS guidelines on neuropathic pain assessment: revised 2009. Eur J Neurol. 2010;17(8):1010–8.PubMed
103.
Bouhassira D, Attal N, Fermanian J, Alchaar H, Gautron M, Masquelier E, Rostaing S, Lanteri-Minet M, Collin E, Grisart J, Boureau F. Development and validation of the Neuropathic Pain Symptom Inventory. Pain. 2004;108(3):248–57.PubMed
104.
Zelman DC, Gore M, Dukes E, Tai KS, Brandenburg N. Validation of a modified version of the brief pain inventory for painful diabetic peripheral neuropathy. J Pain Symptom Manage. 2005;29(4):401–10.PubMed
105.
Backonja MM, Krause SJ. Neuropathic pain questionnaire—short form. Clin J Pain. 2003;19(5):315.PubMed
106.
Bennett M. The LANSS Pain Scale: the Leeds assessment of neuropathic symptoms and signs. Pain. 2001;92:147–57.PubMed
107.
Melzack R. The short-form McGill pain questionnaire. Pain. 1987;30:191–7.PubMed
108.
Vileikyte L, Peyrot M, Bundy EC, et al. The development and validation of a neuropathy and foot ulcer specific quality of life instrument. Diabetes Care. 2003;26:2549–55.PubMed
109.
Vinik E, Hayes R, Oglesby A, Bastyr E, Barlow P, Ford-Molvik S, Vinik A. The development and validation of the Norfolk QOL-DN a new measure of patients’ perception of the effects of diabetes and diabetic neuropathy. Diabetes Technol Ther. 2005;7(3):497–508.PubMed
110.
Poole HM, Murphy P, Nurmikko TJ. Development and preliminary validation of the NePIQoL: a quality-of-life measure for neuropathic pain. J Pain Symptom Manage. 2009;37:233–45.PubMed
111.
Zigmond AS, Snaith RP. The hospital anxiety depression scale. Acta Psychiatr Scand. 1983;67:361–70.PubMed
112.
Finnerup NB, Sindrup SH, Jensen TS. The evidence for pharmacological treatment of neuropathic pain. Pain. 2010;150:573–81.PubMed
113.
Sindrup S, Otto M, Finnerup NB, Jensen TS. Antidepressants in the treatment of neuropathic pain. Basic Clin Pharmacol Toxicol. 2005;96:399–409.PubMed
114.
Ray WA, Meredith S, Thapa PB, et al. Cyclic antidepressants and the risk of sudden cardiac death. Clin Pharmacol Ther. 2004;75:234–41.PubMed
115.
Kajdasz DK, Iyengar S, Desaiah D, et al. Duloxetine for the management of diabetic peripheral neuropathic pain: evidence-based findings from post hoc analysis of three multicentre, randomised, double-blind, placebo-controlled, parallel-group studies. Clin Ther. 2007;29 suppl 2:536–46.
116.
Backonja MM, Beydoun A, Edwards KR, et al. Gabapentin for symptomatic treatment of painful neuropathy in patients with diabetes mellitus. JAMA. 1998;280:1831–6.PubMed
117.
Freeman R, Durso-Decruz E, Emir B. Efficacy, safety, and tolerability of pregabalin treatment for painful diabetic peripheral neuropathy: findings from seven randomised, controlled trials across a range of doses. Diabetes Care. 2008;31:1448–54.PubMed
118.
Kastrup J, Petersen P, Dejard A, et al. Intravenous lidocaine infusion: a new treatment of chronic painful diabetic neuropathy. Pain. 1987;28:69–75.PubMed
119.
Baron R, Mayoral V, Leijon G, Binder A, Steigerwald I, Serpell M. Efficacy and safety of 5% lidocaine (lignocaine) medicated plaster in comparison with pregabalin in patients with postherpetic neuralgia and diabetic polyneuropathy: interim analysis from an open-label, two-stage adaptive, randomized, controlled trial. Clin Drug Investig. 2009;29(4):231–41.PubMed
120.
Harati Y, Gooch C, Swenson M, et al. Double-blind randomised trial of tramadol for the treatment of the pain of diabetic neuropathy. Neurology. 1998;50:1842–6.PubMed
121.
Gimbel JS, Richards P, Portenoy RK. Controlled-release oxycodone for pain in diabetic neuropathy: a randomised controlled trial. Neurology. 2003;60:927–34.PubMed
122.
Bansal D, Bhansali A, Hota D, Chakrabarti A, Dutta P. Amitriptyline vs pregabalin in painful diabetic neuropathy: a randomised double-blind clinical trial. Diabetic Med. 2009;26:1019–26.PubMed
123.
Gilron I, Bailey JM, Tu D, et al. Nortriptyline and gabapentin, alone and in combination for neuropathic pain: a double-blind, randomised controlled crossover trial. Lancet. 2009;374(9697):1252–61.PubMed
124.
Gilron I, Bailey JM, Tu D, et al. Morphine, gabapentin, or their combination for neuropathic pain. N Engl J Med. 2005;352:1324–34.PubMed
125.
Zhang WY, Li Wan Po A. The effectiveness of topically applied capsaicin: a meta-analysis. Eur J Clin Pharm. 1994;46:517–22.
126.
Ziegler D, Nowak H, Kempler P, Vargha P, Low PA. Treatment of symptomatic diabetic Polyneuropathy with alpha-lipoic acid: a meta-analysis. Diabetic Med. 2004;21:114–21.PubMed
127.
Attal N, Cruccu G, Baron R, Haanpää M, Hansson P, Jensen TS, Nurmikko T, European Federation of Neurological Societies. EFNS guidelines on the pharmacological treatment of neuropathic pain: 2010 revision. Eur J Neurol. 2010;17(9):1113–e88.PubMed
128.
NICE Clinical Guideline 96: neuropathic pain. The pharmacological management of neuropathic pain in adults in non-specialist settings. March 2010. www.​nice.​org.​uk.
129.
Bril V, England J, Franklin GM, Backonja M, Cohen J, Del Toro D, Feldman E, Iverson DJ, Perkins B, Russell JW, Zochodne D. Evidence-based guideline: treatment of painful diabetic neuropathy: report of the American Academy of Neurology, the American Association of Neuromuscular and Electrodiagnostic Medicine, and the American Academy of Physical Medicine and Rehabilitation. Neurology. 2011;76(20):1758–65.PubMed
130.
Tesfaye S, Vileikyte L, Rayman G, Sindrup S, Perkins B, Baconja M, Vinik A, Boulton A; on behalf of the Toronto Expert Panel on Diabetic Neuropathy*. Painful diabetic peripheral neuropathy: consensus recommendations on diagnosis, assessment and management. Diabetes Metab Res Rev. doi: 10.​1002/​dmrr.​1225.
131.
Abuaisha BB, Constanzi JB, Boulton AJM. Acupuncture for the treatment of chronic painful diabetic neuropathy: a long-term study. Diabetes Res Clin Pract. 1998;39:115–21.PubMed
132.
Leonard DR, Farooqu MH, Myers S. Restoration of sensation, reduced pain, and improved balance in subjects with diabetic peripheral neuropathy: a double-blind, randomised placebo-controlled study with monochromatic infrared treatment. Diabetes Care. 2004;27:168–72.PubMed
133.
Zinman LH, Ngo M, Ng ET, et al. Low-intensity laser therapy for painful symptoms of diabetic sensorimotor polyneuropathy: a controlled trial. Diabetes Care. 2004;27:921–4.PubMed
134.
Oyibo S, Breislin K, Boulton AJM. Electrical stimulation therapy through stocking electrodes for painful diabetic neuropathy: a double-blind controlled crossover study. Diabet Med. 2004;21:940–4.PubMed
135.
Bosi E, Conti M, Vermigli C, et al. Effectiveness of frequency modulated electromagnetic neural stimulation in the treatment of diabetic peripheral neuropathy. Diabetologia. 2005;48(5):817–23.PubMed
136.
Reichstein L, Labrenz S, Ziegler D, Martin S. Effective treatment of symptomatic diabetic poyneuropathy by high frequency external muscle stimulation. Diabetologia. 2005;48(5):824–8.PubMed
137.
Tesfaye S, Watt J, Benbow SJ, et al. Electrical spinal-cord stimulation for painful diabetic peripheral neuropathy. Lancet. 1996;348:1698–701.PubMed

Be confident that your patient care is up to date

Medicine Matters is being incorporated into Springer Medicine, our new medical education platform. 

Alongside the news coverage and expert commentary you have come to expect from Medicine Matters diabetes, Springer Medicine's complimentary membership also provides access to articles from renowned journals and a broad range of Continuing Medical Education programs. Create your free account »