Skip to content
2000
  1. Home
  2. A-Z Publications
  3. Current Diabetes Reviews
  4. Volume 21, Issue 7
  5. Article
Volume 21, Issue 7
  • ISSN: 1573-3998
  • E-ISSN: 1875-6417

Abstract

The term “Diabetic neuropathy” refers to a collection of clinical and subclinical symptoms caused by problems with the peripheral nervous system. Diabetes, which affects approximately 381 million people worldwide, is the source of dysfunction due to the emergence of microvascular complications. It is anticipated that in the next ten years, Diabetic neuropathy will manifest in about 50% of patients who are currently diagnosed with diabetes. Clinical diagnosis can be established by getting a thorough patient history and exploring the symptoms to rule out alternative causes. Although distal symmetrical polyneuropathy, or just, is the most common and well-researched variant of the disorder, this review will concentrate on it. The multifactorial pathogenesis is linked to various inflammatory, vascular, metabolic, and neurodegenerative illnesses. The three fundamental molecular alterations that lead to the development of diabetic neuropathic pain are oxidative stress, endothelial dysfunction, and chronic inflammation. These three elements are crucial in the development of polyneuropathy because their combination might result in direct axonal damage and nerve ischemia. The purpose of this article was to provide a narrative review of diabetic neuropathy. We provide an overview of the most recent data on biomarkers, the pathogenesis of the illness, the most recent epidemiology of diabetic neuropathy, and the existing screening and diagnosis outcome measures used in both clinical and research contexts.

© 2025 Bentham Science Publishers
Loading

Article metrics loading...

/content/journals/cdr/10.2174/0115733998295741240606104106
2024-06-24
2025-04-15

  • From This Site

    /content/journals/cdr/10.2174/0115733998295741240606104106
    dcterms_title,dcterms_subject,pub_keyword
    -contentType:Contributor -contentType:Concept -contentType:Institution
    10
    5
Loading full text...

Full text loading...

References

  1. AhmadS. MittalM. Diabetic neuropathies.J Int Med Sci Acad2015285153
     [Google Scholar]
  2. Legrand-PoelsS. EsserN. L’hommeL. ScheenA. PaquotN. PietteJ. Free fatty acids as modulators of the NLRP3 inflammasome in obesity/type 2 diabetes.Biochem. Pharmacol.201492113114110.1016/j.bcp.2014.08.013 25175736
     [Google Scholar]
  3. SaeediP. PetersohnI. SalpeaP. Global and regional diabetes prevalence estimates for 2019 and projections for 2030 and 2045: Results from the International Diabetes Federation Diabetes Atlas, 9th edition.Diabetes Res Clin Pract201915710784310.1016/j.diabres.2019.107843 31518657
     [Google Scholar]
  4. SmithS. NormahaniP. LaneT. Hohenschurz-SchmidtD. OliverN. DaviesA.H. Prevention and management strategies for diabetic neuropathy.Life (Basel)2022128118510.3390/life12081185 36013364
     [Google Scholar]
  5. Botas VelascoM. Cervell RodríguezD. Rodríguez MontalbánA.I. Vicente JiménezS. Fernández de Valderrama MartínezI. Actualización en el diagnóstico, tratamiento y prevención de la neuropatía diabética periférica.Angiologia201769317418110.1016/j.angio.2016.06.005
     [Google Scholar]
  6. PunthakeeZ. GoldenbergR. KatzP. Definition, classification and diagnosis of diabetes, prediabetes and metabolic syndrome.Can. J. Diabetes201842Suppl. 1S10S1510.1016/j.jcjd.2017.10.003 29650080
     [Google Scholar]
  7. LotfyM. AdeghateJ. KalaszH. SinghJ. AdeghateE. Chronic complications of diabetes mellitus: A mini review.Curr. Diabetes Rev.201613131010.2174/1573399812666151016101622 26472574
     [Google Scholar]
  8. Méndez-MoralesS.T. Pérez-De MarcosJ.C. Rodríguez-CortésO. Diabetic neuropathy: Molecular approach a treatment opportunity.Vascul. Pharmacol.202214310695410.1016/j.vph.2022.106954 35063655
     [Google Scholar]
  9. DuarteJ.M. Early diabetic neuropathy: A diagnostic challenge.EC Neurology20175204206
     [Google Scholar]
  10. Pop-BusuiR. BoultonA.J.M. FeldmanE.L. Diabetic neuropathy: A position statement by the American Diabetes Association.Diabetes Care201740113615410.2337/dc16‑2042 27999003
     [Google Scholar]
  11. HexN. BartlettC. WrightD. TaylorM. VarleyD. Estimating the current and future costs of Type 1 and Type 2 diabetes in the UK, including direct health costs and indirect societal and productivity costs.Diabet. Med.201229785586210.1111/j.1464‑5491.2012.03698.x 22537247
     [Google Scholar]
  12. FeldmanE.L. CallaghanB.C. Pop-BusuiR. Diabetic neuropathy.Nat. Rev. Dis. Primers2019514110.1038/s41572‑019‑0092‑1 31197153
     [Google Scholar]
  13. García-DíezE. López-OlivaM.E. Caro-VadilloA. Supplementation with a Cocoa-Carob blend, alone or in combination with metformin, attenuates diabetic cardiomyopathy, cardiac oxidative stress and inflammation in Zucker diabetic rats.Antioxidants202211243210.3390/antiox11020432 35204314
     [Google Scholar]
  14. ShahA.K. BhullarS.K. ElimbanV. DhallaN.S. Oxidative stress as a mechanism for functional alterations in cardiac hypertrophy and heart failure.Antioxidants202110693110.3390/antiox10060931 34201261
     [Google Scholar]
  15. AkinciG. NowacekD. CallaghanB. Neuropathy in Type 1 and Type 2 Diabetes.Advances in Pathophysiology and Clinical Management.ChamSpringer2023516610.1007/978‑3‑031‑15613‑7_4
     [Google Scholar]
  16. GylfadottirS.S. ChristensenD.H. NicolaisenS.K. Diabetic polyneuropathy and pain, prevalence, and patient characteristics: A cross-sectional questionnaire study of 5,514 patients with recently diagnosed type 2 diabetes.Pain2020161357458310.1097/j.pain.0000000000001744 31693539
     [Google Scholar]
  17. HepşenS. KeskinD.B. ÇakalE. The assessment of neuropathic pain in patients with prediabetes.Prim. Care Diabetes2023171333710.1016/j.pcd.2022.11.004 36435735
     [Google Scholar]
  18. Pop-BusuiR. Diagnosis And Treatment Of Painful Diabetic Peripheral Neuropathy.Arlington, VAAmerican Diabetes Association202210.2337/db2022‑01
     [Google Scholar]
  19. FreemanR. Diabetic autonomic neuropathy.Handb. Clin. Neurol.2014126637910.1016/B978‑0‑444‑53480‑4.00006‑0 25410215
     [Google Scholar]
  20. SmithS. NormahaniP. LaneT. Hohenschurz-SchmidtD. OliverN. DaviesA.H. Pathogenesis of distal symmetrical polyneuropathy in diabetes.Life (Basel)2022127107410.3390/life12071074 35888162
     [Google Scholar]
  21. AngL. JaiswalM. MartinC. Pop-BusuiR. Glucose control and diabetic neuropathy: Lessons from recent large clinical trials.Curr. Diab. Rep.201414952810.1007/s11892‑014‑0528‑7 25139473
     [Google Scholar]
  22. SelvarajahD. WilkinsonI.D. DaviesJ. GandhiR. TesfayeS. Central nervous system involvement in diabetic neuropathy.Curr. Diab. Rep.201111431032210.1007/s11892‑011‑0205‑z 21667355
     [Google Scholar]
  23. AnandhanarayananA. Diabetic Neuropathies.South Dartmouth, MAEndotext2022
     [Google Scholar]
  24. ElafrosM.A. AndersenH. BennettD.L. Towards prevention of diabetic peripheral neuropathy: Clinical presentation, pathogenesis, and new treatments.Lancet Neurol.2022211092293610.1016/S1474‑4422(22)00188‑0 36115364
     [Google Scholar]
  25. CallaghanB.C. GallagherG. FridmanV. FeldmanE.L. Diabetic neuropathy: What does the future hold?Diabetologia202063589189710.1007/s00125‑020‑05085‑9 31974731
     [Google Scholar]
  26. CallaghanB.C. Central obesity is associated with neuropathy in the severely obese.Mayo Clin. Proc.20209571342135310.1016/j.mayocp.2020.03.025
     [Google Scholar]
  27. SunJ. WangY. ZhangX. ZhuS. HeH. Prevalence of peripheral neuropathy in patients with diabetes: A systematic review and meta-analysis.Prim. Care Diabetes202014543544410.1016/j.pcd.2019.12.005 31917119
     [Google Scholar]
  28. HuangY.C. ChuangY.C. ChiuW.C. Quantitative thermal testing as a screening and follow-up tool for diabetic sensorimotor polyneuropathy in patients with type 2 diabetes and prediabetes.Front. Neurosci.202317111524210.3389/fnins.2023.1115242 37051142
     [Google Scholar]
  29. KangS. ZhongY. LiuD. LiW. Traditional Chinese medicine fumigation as auxiliary treatment of diabetic peripheral neuropathy.Medicine (Baltimore)20211004e2420010.1097/MD.0000000000024200 33530212
     [Google Scholar]
  30. SpalloneV. CiccacciC. LatiniA. BorgianiP. What is in the field for genetics and epigenetics of diabetic neuropathy: The role of microRNAs.J. Diabetes Res.2021202111010.1155/2021/5593608 34660810
     [Google Scholar]
  31. JaiswalM. LauerA. MartinC.L. Peripheral neuropathy in adolescents and young adults with type 1 and type 2 diabetes from the SEARCH for Diabetes in Youth follow-up cohort: A pilot study.Diabetes Care201336123903390810.2337/dc13‑1213 24144652
     [Google Scholar]
  32. NathanD.M. GenuthS. LachinJ. The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus.N. Engl. J. Med.19933291497798610.1056/NEJM199309303291401 8366922
     [Google Scholar]
  33. MartinC.L. AlbersJ.W. Pop-BusuiR. Neuropathy and related findings in the diabetes control and complications trial/epidemiology of diabetes interventions and complications study.Diabetes Care2014371313810.2337/dc13‑2114 24356595
     [Google Scholar]
  34. BoultonA. MalikR. Diabetes mellitus: Neuropathy. Endocrinology: Adult and Pediatric.7th edAmsterdamElsevier2016
     [Google Scholar]
  35. Ismail-BeigiF. CravenT. BanerjiM.A. Effect of intensive treatment of hyperglycaemia on microvascular outcomes in type 2 diabetes: An analysis of the ACCORD randomised trial.Lancet2010376973941943010.1016/S0140‑6736(10)60576‑4 20594588
     [Google Scholar]
  36. BraffettB.H. Gubitosi-KlugR.A. AlbersJ.W. Risk factors for diabetic peripheral neuropathy and cardiovascular autonomic neuropathy in the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications (DCCT/EDIC) study.Diabetes20206951000101010.2337/db19‑1046 32051148
     [Google Scholar]
  37. MaserR.E. SteenkisteA.R. DormanJ.S. Epidemiological correlates of diabetic neuropathy. Report from Pittsburgh Epidemiology of Diabetes Complications Study.Diabetes198938111456146110.2337/diab.38.11.1456 2620781
     [Google Scholar]
  38. JarsoG. AhmedA. FelekeY. The prevalence, clinical features and management of periphral neuropathy among diabetic patients in Tikur Anbessa and St. Paul’s Specialized University Hospitals, Addis Ababa, Ethiopia.Ethiop. Med. J.2011494299311 23409395
     [Google Scholar]
  39. BarbosaM. SaavedraA. OliveiraS. Prevalence and determinants of painful and painless neuropathy in type 1 diabetes mellitus.Front. Endocrinol. (Lausanne)20191040210.3389/fendo.2019.00402 31316463
     [Google Scholar]
  40. CallaghanB.C. XiaR. BanerjeeM. Metabolic syndrome components are associated with symptomatic polyneuropathy independent of glycemic status.Diabetes Care201639580180710.2337/dc16‑0081 26965720
     [Google Scholar]
  41. CallaghanB.C. GaoL. LiY. Diabetes and obesity are the main metabolic drivers of peripheral neuropathy.Ann. Clin. Transl. Neurol.20185439740510.1002/acn3.531 29687018
     [Google Scholar]
  42. World Health OrganizationGlobal status report on alcohol and health 2018.2019Available From: https://www.who.int/publications/i/item/9789241565639
    [Google Scholar]
  43. BrognaraL. MazzottiA. Di MartinoA. FaldiniC. CauliO. Wearable sensor for assessing gait and postural alterations in patients with diabetes: A scoping review.Medicina (Kaunas)20215711114510.3390/medicina57111145 34833363
     [Google Scholar]
  44. ReevesN.D. OrlandoG. BrownS.J. Sensory-motor mechanisms increasing falls risk in diabetic peripheral neuropathy.Medicina (Kaunas)202157545710.3390/medicina57050457 34066681
     [Google Scholar]
  45. GilbertT.R. NoarA. BlalockO. PolonskyW.H. Change in hemoglobin A1c and quality of life with real-time continuous glucose monitoring use by people with insulin-treated diabetes in the landmark study.Diabetes Technol. Ther.202123S1S-35S-3910.1089/dia.2020.0666 33470882
     [Google Scholar]
  46. LindekildeN. Psychiatric disorders as risk factors for type 2 diabetes: An umbrella review of systematic reviews with and without meta-analyses.Diabetes Res. Clin. Pract.2021176108855
     [Google Scholar]
  47. AndreaeS.J. AndreaeL.J. RichmanJ.S. CherringtonA.L. SaffordM.M. Peer-delivered cognitive behavioral training to improve functioning in patients with diabetes: A cluster-randomized trial.Ann. Fam. Med.2020181152310.1370/afm.2469 31937528
     [Google Scholar]
  48. DamciA. SchruersK.R.J. LeueC. FaberC.G. HoeijmakersJ.G.J. Anxiety and depression in small fiber neuropathy.J. Peripher. Nerv. Syst.202227429130110.1111/jns.12514 36168866
     [Google Scholar]
  49. WuC.S. HsuL.Y. WangS.H. Association of depression and diabetes complications and mortality: A population-based cohort study.Epidemiol. Psychiatr. Sci.202029e9610.1017/S2045796020000049 31992379
     [Google Scholar]
  50. OrlandoG. PriorY. ReevesN.D. VileikyteL. Patient and provider perspective of smart wearable technology in diabetic foot ulcer prevention: A systematic review.Medicina (Kaunas)20215712135910.3390/medicina57121359 34946304
     [Google Scholar]
  51. VescoA.T. HowardK.R. AndersonL.M. PapadakisJ.L. HoodK.K. Weissberg-BenchellJ. Examining indirect effects of anxiety on glycated hemoglobin via automatic negative thinking and diabetes-specific distress in adolescents with type 1 diabetes.Can. J. Diabetes202145547348010.1016/j.jcjd.2021.05.002 34176611
     [Google Scholar]
  52. AlrubA.A. Factors associated with health-related quality of life among Jordanian patients with diabetic foot ulcer.J. Diabetes Res.20192019470672010.1155/2019/4706720
     [Google Scholar]
  53. RigorJ. Martins-MendesD. Monteiro-SoaresM. Risk factors for mortality in patients with a diabetic foot ulcer: A cohort study.Eur. J. Intern. Med.20207110711010.1016/j.ejim.2019.11.011 31735544
     [Google Scholar]
  54. TinkianoL. BarrowA. AdebayoA.M. Knowledge and practice of diabetic foot prevention among diabetic patients attending Edward Francis Small Teaching Hospital, Banjul, The Gambia: An institutional-based cross-sectional study.Curr Res Pub Health202332678910.31586/crph.2023.762
     [Google Scholar]
  55. HesterT. KavarthapuV. Etiology, Epidemiology, and Outcomes of Managing Charcot Arthropathy.Foot Ankle Clin.202227358359410.1016/j.fcl.2022.03.002 36096553
     [Google Scholar]
  56. ShoflerD. HamedaniE. SeunJ. Investigating the use of denosumab in the treatment of acute Charcot neuroarthropathy.J. Foot Ankle Surg.202160235435710.1053/j.jfas.2020.09.018 33472754
     [Google Scholar]
  57. BouçanovaF. ChrastR. Metabolic interaction between Schwann cells and axons under physiological and disease conditions.Front. Cell. Neurosci.20201414810.3389/fncel.2020.00148 32547370
     [Google Scholar]
  58. EidS.A. SavelieffM.G. EidA.A. FeldmanE.L. Nox, Nox, are you there? The role of NADPH oxidases in the peripheral nervous system.Antioxid. Redox Signal.2022377-961363010.1089/ars.2021.0135 34861780
     [Google Scholar]
  59. ChandrasekaranK. ZillioxL.A. RussellJ.W. Diabetic neuropathy-research.Microvascular Disease in Diabetes.Hoboken, New JerseyWiley2020129155
     [Google Scholar]
  60. PangL. LianX. LiuH. Understanding diabetic neuropathy: Focus on oxidative stress.Oxid. Med. Cell. Longev.2020202011310.1155/2020/9524635 32832011
     [Google Scholar]
  61. EftekharpourE. FernyhoughP. Oxidative stress and mitochondrial dysfunction associated with peripheral neuropathy in type 1 diabetes.Antioxid. Redox Signal.2022377-957859610.1089/ars.2021.0152 34416846
     [Google Scholar]
  62. SalehA. SabbirM.G. AghanooriM.R. Muscarinic toxin 7 signals via Ca2+/Calmodulin-dependent protein kinase kinase β to augment mitochondrial function and prevent neurodegeneration.Mol. Neurobiol.20205762521253810.1007/s12035‑020‑01900‑x 32198698
     [Google Scholar]
  63. RumoraA.E. LoGrassoG. HaidarJ.A. DolkowskiJ.J. LentzS.I. FeldmanE.L. Chain length of saturated fatty acids regulates mitochondrial trafficking and function in sensory neurons.J. Lipid Res.2019601587010.1194/jlr.M086843 30442656
     [Google Scholar]
  64. EidS.A. RumoraA.E. BeirowskiB. New perspectives in diabetic neuropathy.Neuron2023111172623264110.1016/j.neuron.2023.05.003 37263266
     [Google Scholar]
  65. SinghR. RaoH.K. SinghT.G. Advanced glycated end products (ages) in diabetes and its complications: An insight.Plant Arch.202020138383841
     [Google Scholar]
  66. LiuY. ShaoS. GuoH. Schwann cells apoptosis is induced by high glucose in diabetic peripheral neuropathy.Life Sci.202024811745910.1016/j.lfs.2020.117459 32092332
     [Google Scholar]
  67. NeekhraA. TranJ. PhamK. Memantine, simvastatin, and epicatechin inhibit 7-ketocholesterol-induced apoptosis in retinal pigment epithelial cells but not neurosensory retinal cells in vitro.J. Ophthalmic Vis. Res.202015447048010.18502/jovr.v15i4.7781 33133437
     [Google Scholar]
  68. ChengY. How inflammation dictates diabetic peripheral neuropathy: An enlightening review.CNS Neurosci. Ther.2023 37795833
     [Google Scholar]
  69. ErusalimskyJ.D. The use of the soluble receptor for advanced glycation-end products (sRAGE) as a potential biomarker of disease risk and adverse outcomes.Redox Biol.20214210195810.1016/j.redox.2021.101958 33839083
     [Google Scholar]
  70. ZinggJ.M. VladA. RicciarelliR. Oxidized LDLS as signaling molecules.Antioxidants2021108118410.3390/antiox10081184 34439432
     [Google Scholar]
  71. DurakM.A. OzhanO. TetikB. Effects of apocynin on sciatic nerve injury in rabbits.Biotech. Histochem.202398317217810.1080/10520295.2022.2146195 36440649
     [Google Scholar]
  72. KumarA. MittalR. Nrf2: A potential therapeutic target for diabetic neuropathy.Inflammopharmacology201725439340210.1007/s10787‑017‑0339‑y 28353124
     [Google Scholar]
  73. AkterN. Diabetic peripheral neuropathy: Epidemiology, physiopathology, diagnosis and treatment.Delta Med Coll J201971354810.3329/dmcj.v7i1.40619
     [Google Scholar]
  74. SchreiberA.K. NonesC.F. ReisR.C. ChichorroJ.G. CunhaJ.M. Diabetic neuropathic pain: Physiopathology and treatment.World J. Diabetes20156343244410.4239/wjd.v6.i3.432 25897354
     [Google Scholar]
  75. HerderC. LankischM. ZieglerD. Subclinical inflammation and diabetic polyneuropathy: MONICA/KORA Survey F3 (Augsburg, Germany).Diabetes Care200932468068210.2337/dc08‑2011 19131463
     [Google Scholar]
  76. ZhuT. MengQ. JiJ. ZhangL. LouX. TLR4 and caveolin‐1 in monocytes are associated with inflammatory conditions in diabetic neuropathy.Clin. Transl. Sci.201710317818410.1111/cts.12434 27981790
     [Google Scholar]
  77. MadonnaR. BalistreriC.R. GengY.J. De CaterinaR. Diabetic microangiopathy: Pathogenetic insights and novel therapeutic approaches.Vascul. Pharmacol.2017901710.1016/j.vph.2017.01.004 28137665
     [Google Scholar]
  78. MadonnaR. PieragostinoD. BalistreriC.R. Diabetic macroangiopathy: Pathogenetic insights and novel therapeutic approaches with focus on high glucose-mediated vascular damage.Vascul. Pharmacol.2018107273410.1016/j.vph.2018.01.009 29425894
     [Google Scholar]
  79. MeijerJ.W.G. SmitA.J. SonderenE.V. GroothoffJ.W. EismaW.H. LinksT.P. Symptom scoring systems to diagnose distal polyneuropathy in diabetes: The Diabetic Neuropathy Symptom score.Diabet. Med.2002191196296510.1046/j.1464‑5491.2002.00819.x 12421436
     [Google Scholar]
  80. HellwegR. RaivichG. HartungH.D. HockC. KreutzbergG.W. Axonal transport of endogenous nerve growth factor (NGF) and NGF receptor in experimental diabetic neuropathy.Exp. Neurol.19941301243010.1006/exnr.1994.1181 7821393
     [Google Scholar]
  81. ViaderA. SasakiY. KimS. Aberrant Schwann cell lipid metabolism linked to mitochondrial deficits leads to axon degeneration and neuropathy.Neuron201377588689810.1016/j.neuron.2013.01.012 23473319
     [Google Scholar]
  82. YagihashiS. MizukamiH. SugimotoK. Mechanism of diabetic neuropathy: Where are we now and where to go?J. Diabetes Investig.201121183210.1111/j.2040‑1124.2010.00070.x 24843457
     [Google Scholar]
  83. ObrosovaI.G. DrelV.R. PacherP. Oxidative-nitrosative stress and poly(ADP-ribose) polymerase (PARP) activation in experimental diabetic neuropathy: The relation is revisited.Diabetes200554123435344110.2337/diabetes.54.12.3435 16306359
     [Google Scholar]
  84. BierhausA. HaslbeckK.M. HumpertP.M. Loss of pain perception in diabetes is dependent on a receptor of the immunoglobulin superfamily.J. Clin. Invest.2004114121741175110.1172/JCI18058 15599399
     [Google Scholar]
  85. YagihashiS. YamagishiS.I. Wada RiR. Neuropathy in diabetic mice overexpressing human aldose reductase and effects of aldose reductase inhibitor.Brain2001124122448245810.1093/brain/124.12.2448 11701599
     [Google Scholar]
  86. SugimotoK. NishizawaY. HoriuchiS. YagihashiS. Localization in human diabetic peripheral nerve of N ε -carboxymethyllysine-protein adducts, an advanced glycation endproduct.Diabetologia199740121380138710.1007/s001250050839 9447944
     [Google Scholar]
  87. WadaR. NishizawaY. YagihashiN. Effects of OPB‐9195, anti‐glycation agent, on experimental diabetic neuropathy.Eur. J. Clin. Invest.200131651352010.1046/j.1365‑2362.2001.00826.x 11422401
     [Google Scholar]
  88. HauptE. LedermannH. KöpckeW. Benfotiamine in the treatment of diabetic polyneuropathy - a three-week randomized, controlled pilot study (BEDIP Study).Int. J. Clin. Pharmacol. Ther.2005432717710.5414/CPP43071 15726875
     [Google Scholar]
  89. AbbottC.A. MalikR.A. van RossE.R.E. KulkarniJ. BoultonA.J.M. Prevalence and characteristics of painful diabetic neuropathy in a large community-based diabetic population in the U.K.Diabetes Care201134102220222410.2337/dc11‑1108 21852677
     [Google Scholar]
  90. RaputovaJ. SrotovaI. VlckovaE. Sensory phenotype and risk factors for painful diabetic neuropathy: A cross-sectional observational study.Pain2017158122340235310.1097/j.pain.0000000000001034 28858986
     [Google Scholar]
  91. ThemistocleousA.C. RamirezJ.D. ShilloP.R. The Pain in Neuropathy Study (PiNS): A cross-sectional observational study determining the somatosensory phenotype of painful and painless diabetic neuropathy.Pain201615751132114510.1097/j.pain.0000000000000491 27088890
     [Google Scholar]
  92. KrämerH.H. RolkeR. BickelA. BirkleinF. Thermal thresholds predict painfulness of diabetic neuropathies.Diabetes Care200427102386239110.2337/diacare.27.10.2386 15451905
     [Google Scholar]
  93. ShilloP. SloanG. GreigM. Painful and painless diabetic neuropathies: What is the difference?Curr. Diab. Rep.20191963210.1007/s11892‑019‑1150‑5 31065863
     [Google Scholar]
  94. BönhofG.J. HerderC. StromA. PapanasN. RodenM. ZieglerD. Emerging biomarkers, tools, and treatments for diabetic polyneuropathy.Endocr. Rev.201940115319210.1210/er.2018‑00107 30256929
     [Google Scholar]
  95. ZieglerD. Current concepts in the management of diabetic polyneuropathy.Curr. Diabetes Rev.20117320822010.2174/157339911795843113 21534920
     [Google Scholar]
  96. FeldmanE.L. StevensM.J. ThomasP.K. BrownM.B. CanalN. GreeneD.A. A practical two-step quantitative clinical and electrophysiological assessment for the diagnosis and staging of diabetic neuropathy.Diabetes Care199417111281128910.2337/diacare.17.11.1281 7821168
     [Google Scholar]
  97. MalikR.A. Andag-SilvaA. DejthevapornC. Diagnosing peripheral neuropathy in South‐East Asia: A focus on diabetic neuropathy.J. Diabetes Investig.20201151097110310.1111/jdi.13269 32268012
     [Google Scholar]
  98. SingletonJ.R. MarcusR.L. JacksonJ.E. K. LessardM. GrahamT.E. SmithA.G. Exercise increases cutaneous nerve density in diabetic patients without neuropathy.Ann. Clin. Transl. Neurol.201411084484910.1002/acn3.125 25493275
     [Google Scholar]
  99. ThornalleyP.J. Glycation in diabetic neuropathy: Characteristics, consequences, causes, and therapeutic options.Int. Rev. Neurobiol.200250375710.1016/S0074‑7742(02)50072‑6 12198817
     [Google Scholar]
  100. AndersenS.T. WitteD.R. DalsgaardE.M. Risk factors for incident diabetic polyneuropathy in a cohort with screen-detected type 2 diabetes followed for 13 years: ADDITION-Denmark.Diabetes Care20184151068107510.2337/dc17‑2062 29487078
     [Google Scholar]
  101. ZhuT. MengQ. JiJ. LouX. ZhangL. Toll-like receptor 4 and tumor necrosis factor-alpha as diagnostic biomarkers for diabetic peripheral neuropathy.Neurosci. Lett.2015585283210.1016/j.neulet.2014.11.020 25445373
     [Google Scholar]
  102. RudofskyG.Jr ReismannP. WitteS. Asp299Gly and Thr399Ile genotypes of the TLR4 gene are associated with a reduced prevalence of diabetic neuropathy in patients with type 2 diabetes.Diabetes Care200427117918310.2337/diacare.27.1.179 14693986
     [Google Scholar]
  103. PradeepaR. SurendarJ. IndulekhaK. ChellaS. AnjanaR.M. MohanV. Association of serum adiponectin with diabetic microvascular complications among south Indian type 2 diabetic subjects — (CURES-133).Clin. Biochem.2015481-2333810.1016/j.clinbiochem.2014.10.009 25445230
     [Google Scholar]
  104. GroenerJ. ReismannP. FlemingT. C332C genotype of glyoxalase 1 and its association with late diabetic complications.Exp. Clin. Endocrinol. Diabetes2013121743643910.1055/s‑0033‑1345124 23775136
     [Google Scholar]
  105. SugimotoK. YasujimaM. YagihashiS. Role of advanced glycation end products in diabetic neuropathy.Curr. Pharm. Des.2008141095396110.2174/138161208784139774 18473845
     [Google Scholar]
  106. CallaghanB.C. Enhanced glucose control for preventing and treating diabetic neuropathy.Cochrane Database Syst. Rev.201266CD00754310.1002/14651858.CD007543.pub2
     [Google Scholar]
  107. VárkonyiT. KöreiA. PutzZ. Advances in the management of diabetic neuropathy.Minerva Med.2017108541943710.23736/S0026‑4806.17.05257‑0 28541026
     [Google Scholar]
  108. StinoA.M. RumoraA.E. KimB. FeldmanE.L. Evolving concepts on the role of dyslipidemia, bioenergetics, and inflammation in the pathogenesis and treatment of diabetic peripheral neuropathy.J. Peripher. Nerv. Syst.2020252768410.1111/jns.12387 32412144
     [Google Scholar]
  109. AzmiS. AlamU. BurgessJ. MalikR.A. State-of-the-art pharmacotherapy for diabetic neuropathy.Expert Opin. Pharmacother.2021221556810.1080/14656566.2020.1812578 32866410
     [Google Scholar]
  110. AghiliR. MalekM. TanhaK. MottaghiA. The effect of bariatric surgery on peripheral polyneuropathy: A systematic review and meta-analysis.Obes. Surg.20192993010302010.1007/s11695‑019‑04004‑1 31256355
     [Google Scholar]
  111. SingletonJ.R. MarcusR.L. LessardM.K. JacksonJ.E. SmithA.G. Supervised exercise improves cutaneous reinnervation capacity in metabolic syndrome patients.Ann. Neurol.201577114615310.1002/ana.24310 25388934
     [Google Scholar]
  112. SmithA.G. RussellJ. FeldmanE.L. Lifestyle intervention for pre-diabetic neuropathy.Diabetes Care20062961294129910.2337/dc06‑0224 16732011
     [Google Scholar]
  113. ZieglerD. HanefeldM. RuhnauK.J. Treatment of symptomatic diabetic peripheral neuropathy with the anti-oxidant α-lipoic acid. A 3-week multicentre randomized controlled trial (ALADIN Study).Diabetologia199538121425143310.1007/BF00400603 8786016
     [Google Scholar]
  114. MijnhoutG.S. Alpha lipoic acid for symptomatic peripheral neuropathy in patients with diabetes: A meta-analysis of randomized controlled trials.Int. J. Endocrinol.2012201245627910.1155/2012/456279
     [Google Scholar]
  115. AttalN. CruccuG. BaronR. EFNS guidelines on the pharmacological treatment of neuropathic pain: 2010 revision.Eur. J. Neurol.20101791113e8810.1111/j.1468‑1331.2010.02999.x 20402746
     [Google Scholar]
  116. SindrupS.H. OttoM. FinnerupN.B. JensenT.S. Antidepressants in the treatment of neuropathic pain.Basic Clin. Pharmacol. Toxicol.200596639940910.1111/j.1742‑7843.2005.pto_96696601.x 15910402
     [Google Scholar]
  117. RosenbergerD.C. BlechschmidtV. TimmermanH. WolffA. TreedeR.D. Challenges of neuropathic pain: Focus on diabetic neuropathy.J. Neural Transm. (Vienna)2020127458962410.1007/s00702‑020‑02145‑7 32036431
     [Google Scholar]
  118. ShoaibA. AzmiL. PalS. Integrating nanotechnology with naturally occurring phytochemicals in neuropathy induced by diabetes.J. Mol. Liq.202235011818910.1016/j.molliq.2021.118189
     [Google Scholar]
  119. TajmohammadiA. RazaviB.M. HosseinzadehH. Silybum marianum (milk thistle) and its main constituent, silymarin, as a potential therapeutic plant in metabolic syndrome: A review.Phytother. Res.201832101933194910.1002/ptr.6153 30015401
     [Google Scholar]
  120. TanaseD.M. GosavE.M. AntonM.I. Oxidative stress and NRF2/KEAP1/ARE pathway in diabetic kidney disease (DKD): New perspectives.Biomolecules2022129122710.3390/biom12091227 36139066
     [Google Scholar]
  121. ZhangJ. WuC. GaoL. DuG. QinX. Astragaloside IV derived from Astragalus membranaceus: A research review on the pharmacological effects.Adv. Pharmacol.2020878911210.1016/bs.apha.2019.08.002 32089240
     [Google Scholar]
  122. LaiQ. ZhouB. CuiZ. Development of a metabolite-based deep learning algorithm for clinical precise diagnosis of the progression of diabetic kidney disease.Biomed. Signal Process. Control20238310462510.1016/j.bspc.2023.104625
     [Google Scholar]
  123. PottathilS. NainP. MorsyM.A. Mechanisms of antidiabetic activity of methanolic extract of Punica granatum leaves in nicotinamide/streptozotocin-induced type 2 diabetes in rats.Plants2020911160910.3390/plants9111609 33228177
     [Google Scholar]
  124. Shane-McWhorterL. Dietary supplements for diabetes: An evaluation of commonly used products.Diabetes Spectr.200922420621310.2337/diaspect.22.4.206
     [Google Scholar]
  125. MahmoodK.T. MugalT. HaqI.U. Moringa oleifera: A natural gift-A review.J Pharma Sci Res2010211775
     [Google Scholar]
  126. Al-AdwaniD.G. RennoW.M. OrabiK.Y. Neurotherapeutic effects of Ginkgo biloba extract and its terpene trilactone, ginkgolide B, on sciatic crush injury model: A new evidence.PLoS One20191412e022662610.1371/journal.pone.0226626 31877172
     [Google Scholar]
  127. SloanG. SelvarajahD. TesfayeS. Pathogenesis, diagnosis and clinical management of diabetic sensorimotor peripheral neuropathy.Nat. Rev. Endocrinol.202117740042010.1038/s41574‑021‑00496‑z 34050323
     [Google Scholar]
  128. SloanG. AlamU. SelvarajahD. TesfayeS. The treatment of painful diabetic neuropathy.Curr. Diabetes Rev.2022185e07072119455610.2174/1573399817666210707112413 34238163
     [Google Scholar]
  129. AlamU. To be, or not to be … a biomarker? A question to the FDA.Clin. Ther.20214391438144010.1016/j.clinthera.2021.08.010 34535276
     [Google Scholar]
  130. AkterS. ChoubeyM. MohibM.M. ArbeeS. SagorM.A.T. MohiuddinM.S. Stem cell therapy in diabetic polyneuropathy: Recent advancements and future directions.Brain Sci.202313225510.3390/brainsci13020255 36831798
     [Google Scholar]
/content/journals/cdr/10.2174/0115733998295741240606104106
Loading
An Overview on Diabetic Neuropathy
Curr. Diabetes Rev. 21, E240624231265 (2025); https://doi.org/10.2174/0115733998295741240606104106
/content/journals/cdr/10.2174/0115733998295741240606104106
/content/journals/cdr/10.2174/0115733998295741240606104106
Loading

Data & Media loading...


  • Article Type:     Review Article
Keyword(s): Diabetic neuropathy; diabetic polyneuropathy; diagnosis; endothelial dysfunction; inflammation; oxidative stress

Most Cited Most Cited RSS feed

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error
Please enter a valid_number test