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image of The Role of Novel Biomarkers in the Early Management of Peripheral Diabetic Neuropathy

Abstract

Diabetes can frequently result in peripheral diabetic neuropathy (PDN), a life-threatening illness that impairs the motor and sensory abilities of peripheral nerves. Prompt identification and management of peripheral neuropathy are essential to avert permanent nerve impairment and enhance the well-being of affected individuals. In addition, axonal degeneration is usually detected at a late stage of the disease and serves as a basis for developing modern diagnostic techniques. Novel biomarkers that can detect PDN early and track its development are thus required. In this review, we highlight the most recent developments in identifying and verifying putative biomarkers for PDN, emphasizing their connections to the pathophysiology and clinical presentations of the illness. The challenges and opportunities for developing biomarker-based diagnostic and therapeutic strategies for PDN are also discussed. It is suggested that biomarkers help predict the response and outcome of PDN treatments, such as poly (ADP-ribose) polymerase inhibitors and regenerative medicine.

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2025-05-27
2025-09-26

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References

  1. Abbott C.A. Malik R.A. van Ross E.R.E. Kulkarni J. Boulton A.J.M. Prevalence and characteristics of painful diabetic neuropathy in a large community-based diabetic population in the U.K. Diabetes Care 2011 34 10 2220 2224 10.2337/dc11‑1108 21852677
    [Google Scholar]
  2. Vinik AI Nevoret ML Casellini C Parson H Diabetic neuropathy. Endocrinol Metab Clin North Am 2013 42 4 747 787 10.1016/j.ecl.2013.06.001 24286949
    [Google Scholar]
  3. Edwards J.L. Vincent A.M. Cheng H.T. Feldman E.L. Diabetic neuropathy: Mechanisms to management. Pharmacol. Ther. 2008 120 1 1 34 10.1016/j.pharmthera.2008.05.005 18616962
    [Google Scholar]
  4. Forsblom C.M. Sane T. Groop P.H. Tötterman K.J. Kallio M. Saloranta C. Laasonen L. Summanen P. Lepäntalo M. Laatikainen L. Matikainen E. Teppo A.M. Koskimies S. Groop L. Risk factors for mortality in Type II (non-insulin-dependent) diabetes: Evidence of a role for neuropathy and a protective effect of HLA-DR4. Diabetologia 1998 41 11 1253 1262 10.1007/s001250051062 9833930
    [Google Scholar]
  5. Soedamah-Muthu S.S. Chaturvedi N. Witte D.R. Stevens L.K. Porta M. Fuller J.H. Relationship between risk factors and mortality in type 1 diabetic patients in Europe: The EURODIAB prospective complications study (PCS). Diabetes Care 2008 31 7 1360 1366 10.2337/dc08‑0107 18375412
    [Google Scholar]
  6. Coppini D.V. Bowtell P.A. Weng C. Young P.J. Sönksen P.H. Showing neuropathy is related to increased mortality in diabetic patients — a survival analysis using an accelerated failure time model. J. Clin. Epidemiol. 2000 53 5 519 523 10.1016/S0895‑4356(99)00170‑5 10812325
    [Google Scholar]
  7. Rolim LC da Silva EM Flumignan RL Abreu MM Dib SA Acetyl‐L‐carnitine for the treatment of diabetic peripheral neuropathy. Cochrane Database Syst Rev 2019 6 6 CD011265 10.1002/14651858.CD011265.pub2 31201734
    [Google Scholar]
  8. Girach A. Julian T.H. Varrassi G. Paladini A. Vadalouka A. Zis P. Quality of life in painful peripheral neuropathies: A systematic review. Pain Res. Manag. 2019 2019 1 9 10.1155/2019/2091960 31249636
    [Google Scholar]
  9. Sadosky A. Mardekian J. Parsons B. Hopps M. Bienen E.J. Markman J. Healthcare utilization and costs in diabetes relative to the clinical spectrum of painful diabetic peripheral neuropathy. J. Diabetes Complications 2015 29 2 212 217 10.1016/j.jdiacomp.2014.10.013 25498300
    [Google Scholar]
  10. Nagpal A.S. Leet J. Egan K. Garza R. Diabetic neuropathy: A critical, narrative review of published data from 2019. Curr. Pain Headache Rep. 2021 25 3 15 10.1007/s11916‑020‑00928‑x 33630186
    [Google Scholar]
  11. Cheng M.K. Guo Y.Y. Kang X.N. Zhang L. Wang D. Ren H.H. Yuan G. Advances in cardiovascular-related biomarkers to predict diabetic peripheral neuropathy. World J. Diabetes 2023 14 8 1226 1233 10.4239/wjd.v14.i8.1226 37664477
    [Google Scholar]
  12. Petropoulos I.N. Ponirakis G. Khan A. Almuhannadi H. Gad H. Malik R.A. Diagnosing diabetic neuropathy: Something old, something new. Diabetes Metab. J. 2018 42 4 255 269 10.4093/dmj.2018.0056 30136449
    [Google Scholar]
  13. Fan Q. Gordon Smith A. Recent updates in the treatment of diabetic polyneuropathy. Fac. Rev. 2022 11 30 10.12703/r/11‑30 36311537
    [Google Scholar]
  14. Marshall A. Alam U. Themistocleous A. Calcutt N. Marshall A. Novel and emerging electrophysiological biomarkers of diabetic neuropathy and painful diabetic neuropathy. Clin. Ther. 2021 43 9 1441 1456 10.1016/j.clinthera.2021.03.020 33906790
    [Google Scholar]
  15. Pop-Busui R. Boulton A.J.M. Feldman E.L. Bril V. Freeman R. Malik R.A. Sosenko J.M. Ziegler D. Diabetic neuropathy: A position statement by the American Diabetes Association. Diabetes Care 2017 40 1 136 154 10.2337/dc16‑2042 27999003
    [Google Scholar]
  16. Boulton AJ Vinik AI Arezzo JC Bril V Feldman EL Freeman R Malik RA Maser RE Sosenko JM Ziegler D Diabetic neuropathies: A statement by the American Diabetes Association. Diabetes Care 2005 28 4 956 962 10.2337/diacare.28.4.956 15793206
    [Google Scholar]
  17. Sinnreich M. Taylor B.V. Dyck P.J.B. Diabetic neuropathies. Neurologist 2005 11 2 63 79 10.1097/01.nrl.0000156314.24508.ed 15733329
    [Google Scholar]
  18. Solomon S.D. Chew E. Duh E.J. Sobrin L. Sun J.K. VanderBeek B.L. Wykoff C.C. Gardner T.W. Diabetic retinopathy: A position statement by the American Diabetes Association. Diabetes Care 2017 40 3 412 418 10.2337/dc16‑2641 28223445
    [Google Scholar]
  19. Ziegler D. Diabetic peripheral neuropathy. Wiley 2010 615 634 10.1002/9781444324808.ch38
    [Google Scholar]
  20. Zhuang Y. Lin X. Chen X. Wu X. Zhang J. Fibrinogen function indexes are potential biomarkers of diabetic peripheral neuropathy. Diabetol. Metab. Syndr. 2022 14 1 13 10.1186/s13098‑021‑00777‑7 35042559
    [Google Scholar]
  21. M S.L. O P. Inflammatory biomarkers as a part of diagnosis in diabetic peripheral neuropathy. J. Diabetes Metab. Disord. 2021 20 1 869 882 10.1007/s40200‑021‑00734‑1 34222094
    [Google Scholar]
  22. Yasuda H. Terada M. Maeda K. Kogawa S. Sanada M. Haneda M. Kashiwagi A. Kikkawa R. Diabetic neuropathy and nerve regeneration. Prog. Neurobiol. 2003 69 4 229 285 10.1016/S0301‑0082(03)00034‑0 12757748
    [Google Scholar]
  23. Tomlinson D.R. Fernyhough P. Diemel L.T. Role of neurotrophins in diabetic neuropathy and treatment with nerve growth factors. Diabetes 1997 46 S43 S49.(Suppl. 2) 10.2337/diab.46.2.S43 9285498
    [Google Scholar]
  24. Ismail C.A.N. Aziz C.B.A. Suppian R. Long I. Imbalanced oxidative stress and pro-inflammatory markers differentiate the development of diabetic neuropathy variants in streptozotocin-induced diabetic rats. J. Diabetes Metab. Disord. 2018 17 2 129 136 10.1007/s40200‑018‑0350‑x 30918846
    [Google Scholar]
  25. Feldman E.L. Nave K.A. Jensen T.S. Bennett D.L.H. New horizons in diabetic neuropathy: Mechanisms, bioenergetics, and pain. Neuron 2017 93 6 1296 1313 10.1016/j.neuron.2017.02.005 28334605
    [Google Scholar]
  26. Pittenger G.L. Ray M. Burcus N.I. McNulty P. Basta B. Vinik A.I. Intraepidermal nerve fibers are indicators of small-fiber neuropathy in both diabetic and nondiabetic patients. Diabetes Care 2004 27 8 1974 1979 10.2337/diacare.27.8.1974 15277426
    [Google Scholar]
  27. Chilton L. Middlemas A. Gardiner N. Tomlinson D.R. The p75 neurotrophin receptor appears in plasma in diabetic rats?characterisation of a potential early test for neuropathy. Diabetologia 2004 47 11 1924 1930 10.1007/s00125‑004‑1550‑0 15558233
    [Google Scholar]
  28. Skapek S.X. Ferrari A. Gupta A.A. Lupo P.J. Butler E. Shipley J. Barr F.G. Hawkins D.S. Viswanathan V. Rhabdomyosarcoma. Nat. Rev. Dis. Primers 2019 5 1 1 8.1 10.1038/s41572‑018‑0051‑2 30617281
    [Google Scholar]
  29. Li J. Guan R. Pan L. Mechanism of Schwann cells in diabetic peripheral neuropathy: A review. Medicine 2023 102 1 e32653 10.1097/MD.0000000000032653 36607875
    [Google Scholar]
  30. Elafros M.A. Andersen H. Bennett D.L. Savelieff M.G. Viswanathan V. Callaghan B.C. Feldman E.L. Towards prevention of diabetic peripheral neuropathy: Clinical presentation, pathogenesis, and new treatments. Lancet Neurol. 2022 21 10 922 936 10.1016/S1474‑4422(22)00188‑0 36115364
    [Google Scholar]
  31. Lin T. Gargya A. Singh H. Sivanesan E. Gulati A. Mechanism of peripheral nerve stimulation in chronic pain. Pain Med. 2020 21 S6 S12.S12.(Suppl. 1) 10.1093/pm/pnaa164 32804230
    [Google Scholar]
  32. Previtali S.C. Peripheral nerve development and the pathogenesis of peripheral neuropathy: The sorting point. Neurotherapeutics 2021 18 4 2156 2168 10.1007/s13311‑021‑01080‑z 34244926
    [Google Scholar]
  33. Hoke A. Cerri F. Fisgin A. Riva N. Quattrini A. Normal structure and pathological features in peripheral neuropathies. J. Peripher. Nerv. Syst. 2021 26 S2 S11 S20.S12.(Suppl. 1) 10.1111/jns.12462 34768313
    [Google Scholar]
  34. Bosch-Queralt M. Fledrich R. Stassart R.M. Schwann cell functions in peripheral nerve development and repair. Neurobiol. Dis. 2023 176 105952 10.1016/j.nbd.2022.105952 36493976
    [Google Scholar]
  35. Ong Sio L.C. Hom B. Garg S. Abd-Elsayed A. Mechanism of action of peripheral nerve stimulation for chronic pain: A narrative review. Int. J. Mol. Sci. 2023 24 5 4540 10.3390/ijms24054540 36901970
    [Google Scholar]
  36. Salzer J.L. Schwann cell myelination. Cold Spring Harb. Perspect. Biol. 2015 7 8 a020529 10.1101/cshperspect.a020529 26054742
    [Google Scholar]
  37. Monje M. Myelin plasticity and nervous system function. Annu. Rev. Neurosci. 2018 41 1 61 76 10.1146/annurev‑neuro‑080317‑061853 29986163
    [Google Scholar]
  38. Sloan G. Selvarajah D. Tesfaye S. Pathogenesis, diagnosis and clinical management of diabetic sensorimotor peripheral neuropathy. Nat. Rev. Endocrinol. 2021 17 7 400 420 10.1038/s41574‑021‑00496‑z 34050323
    [Google Scholar]
  39. Du W. Wang N. Li F. Jia K. An J. Liu Y. Wang Y. Zhu L. Zhao S. Hao J. STAT3 phosphorylation mediates high glucose—impaired cell autophagy in an HDAC1‐dependent and ‐independent manner in Schwann cells of diabetic peripheral neuropathy. FASEB J. 2019 33 7 8008 8021 10.1096/fj.201900127R 30913399
    [Google Scholar]
  40. Liu Y. Shao S. Guo H. Schwann cells apoptosis is induced by high glucose in diabetic peripheral neuropathy. Life Sci. 2020 248 117459 10.1016/j.lfs.2020.117459 32092332
    [Google Scholar]
  41. DiAntonio A. Axon degeneration: Mechanistic insights lead to therapeutic opportunities for the prevention and treatment of peripheral neuropathy. Pain 2019 160 1 S17 S22.(Suppl. 1) 10.1097/j.pain.0000000000001528 31008845
    [Google Scholar]
  42. Modrak M. Talukder M.A.H. Gurgenashvili K. Noble M. Elfar J.C. Peripheral nerve injury and myelination: Potential therapeutic strategies. J. Neurosci. Res. 2020 98 5 780 795 10.1002/jnr.24538 31608497
    [Google Scholar]
  43. Langer H.T. Afzal S. Kempa S. Spuler S. Nerve damage induced skeletal muscle atrophy is associated with increased accumulation of intramuscular glucose and polyol pathway intermediates. Sci. Rep. 2020 10 1 1908 10.1038/s41598‑020‑58213‑1 32024865
    [Google Scholar]
  44. Freeman O.J. Unwin R.D. Dowsey A.W. Begley P. Ali S. Hollywood K.A. Rustogi N. Petersen R.S. Dunn W.B. Cooper G.J.S. Gardiner N.J. Metabolic dysfunction is restricted to the sciatic nerve in experimental diabetic neuropathy. Diabetes 2016 65 1 228 238 10.2337/db15‑0835 26470786
    [Google Scholar]
  45. Velissaris D. Pantzaris N.D. Platanaki C. Antonopoulou N. Gogos C. Procalcitonin as a diagnostic and prognostic marker in diabetic foot infection. A current literature review. Rom. J. Intern. Med. 2018 56 1 3 8 10.1515/rjim‑2017‑0039 29028632
    [Google Scholar]
  46. Presta M. Camozzi M. Salvatori G. Rusnati M. Role of the soluble pattern recognition receptor PTX3 in vascular biology. J. Cell. Mol. Med. 2007 11 4 723 738 10.1111/j.1582‑4934.2007.00061.x 17760835
    [Google Scholar]
  47. Abu Seman N Witasp A Wan Mohamud WN Anderstam B Brismar K Stenvinkel P Gu HF Evaluation of the association of plasma pentraxin 3 levels with type 2 diabetes and diabetic nephropathy in a Malay population. J Diabetes Res 2013 2013 298019 10.1155/2013/298019 24350299
    [Google Scholar]
  48. Bao P. Kodra A. Tomic-Canic M. Golinko M.S. Ehrlich H.P. Brem H. The role of vascular endothelial growth factor in wound healing. J. Surg. Res. 2009 153 2 347 358 10.1016/j.jss.2008.04.023 19027922
    [Google Scholar]
  49. Avitabile S. Odorisio T. Madonna S. Eyerich S. Guerra L. Eyerich K. Zambruno G. Cavani A. Cianfarani F. Interleukin-22 promotes wound repair in diabetes by improving keratinocyte pro-healing functions. J. Invest. Dermatol. 2015 135 11 2862 2870 10.1038/jid.2015.278 26168231
    [Google Scholar]
  50. Pop-Busui R. Ang L. Holmes C. Gallagher K. Feldman E.L. Inflammation as a therapeutic target for diabetic neuropathies. Curr. Diab. Rep. 2016 16 3 29 10.1007/s11892‑016‑0727‑5 26897744
    [Google Scholar]
  51. BhoirPv Gb Jadhav MauryaAk An insight to the biomarkers and potential new diagnostic tool for diabetic neuropathy. wjpr 2018 8 2
    [Google Scholar]
  52. Molines L. Darmon P. Raccah D. Charcot’s foot: Newest findings on its pathophysiology, diagnosis and treatment. Diabetes Metab. 2010 36 4 251 255 10.1016/j.diabet.2010.04.002 20570543
    [Google Scholar]
  53. Giorgino F. Laviola L. Cavallo Perin P. Solnica B. Fuller J. Chaturvedi N. Factors associated with progression to macroalbuminuria in microalbuminuric Type 1 diabetic patients: The EURODIAB Prospective Complications Study. Diabetologia 2004 47 6 1020 1028 10.1007/s00125‑004‑1413‑8 15170497
    [Google Scholar]
  54. El-Badawy M.A. Farrag D.A.B. Abd El-Rehem S.M.R. El-Mahdi A.R. El-Sherbeny A.A. Abdel Hady E.A.M. Abdel-Sattar H.A. Abdelaziz D.M. Tumor necrosis factor-α is a novel biomarker for peripheral neuropathy in type II diabetes mellitus: A clinical and electrophysiological study. Egypt. Rheumatol. Rehabil. 2017 44 2 83 90 10.4103/1110‑161X.205663
    [Google Scholar]
  55. Cheng Y. Chen Y. Li K. Liu S. Pang C. Gao L. Xie J. Wenjing L.V. Yu H. Deng B. How inflammation dictates diabetic peripheral neuropathy: An enlightening review. CNS Neurosci. Ther. 2024 30 4 e14477 10.1111/cns.14477 37795833
    [Google Scholar]
  56. Fujita Y. Murakami T. Nakamura A. Recent advances in biomarkers and regenerative medicine for diabetic neuropathy. Int. J. Mol. Sci. 2021 22 5 2301 10.3390/ijms22052301 33669048
    [Google Scholar]
  57. Baka P. Escolano-Lozano F. Birklein F. Systemic inflammatory biomarkers in painful diabetic neuropathy. J. Diabetes Complications 2021 35 10 108017 10.1016/j.jdiacomp.2021.108017 34389235
    [Google Scholar]
  58. Okdahl T. Brock C. Fløyel T. Wegeberg A.M.L. Jakobsen P.E. Ejskjaer N. Pociot F. Brock B. Størling J. Increased levels of inflammatory factors are associated with severity of polyneuropathy in type 1 diabetes. Clin. Endocrinol. 2020 93 4 419 428 10.1111/cen.14261 32497255
    [Google Scholar]
  59. Qiao X. Zhang S. Zhao W. Ye H. Yang Y. Zhang Z. Miao Q. Hu R. Li Y. Lu B. Serum phosphorylated neurofilament-heavy chain, a potential biomarker, is associated with peripheral neuropathy in patients with type 2 diabetes. Medicine 2015 94 44 e1908 10.1097/MD.0000000000001908 26554790
    [Google Scholar]
  60. Rossor A.M. Liu C-H. Petzold A. Malaspina A. Laura M. Greensmith L. Reilly M.M. Plasma neurofilament heavy chain is not a useful biomarker in Charcot-Marie-Tooth disease. Muscle Nerve 2016 53 6 972 975 10.1002/mus.25124 27015106
    [Google Scholar]
  61. Morgenstern J. Groener J.B. Jende J.M.E. Kurz F.T. Strom A. Göpfert J. Kender Z. Le Marois M. Brune M. Kuner R. Herzig S. Roden M. Ziegler D. Bendszus M. Szendroedi J. Nawroth P. Kopf S. Fleming T. Neuron-specific biomarkers predict hypo- and hyperalgesia in individuals with diabetic peripheral neuropathy. Diabetologia 2021 64 12 2843 2855 10.1007/s00125‑021‑05557‑6 34480211
    [Google Scholar]
  62. Li J. Zhang H. Xie M. Yan L. Chen J. Wang H. NSE, a potential biomarker, is closely connected to diabetic peripheral neuropathy. Diabetes Care 2013 36 11 3405 3410 10.2337/dc13‑0590 23846809
    [Google Scholar]
  63. Sun Q. Tang D.D. Yin E.G. Wei L.L. Chen P. Deng S.P. Tu L.L. Diagnostic significance of serum levels of nerve growth factor and brain derived neurotrophic factor in diabetic peripheral neuropathy. Med. Sci. Monit. 2018 24 5943 5950 10.12659/MSM.909449 30145601
    [Google Scholar]
  64. Baldimtsi E. Whiss P.A. Wahlberg J. Systemic biomarkers of microvascular alterations in type 1 diabetes associated neuropathy and nephropathy - A prospective long-term follow-up study. J. Diabetes Complications 2023 37 12 108635 10.1016/j.jdiacomp.2023.108635 37989066
    [Google Scholar]
  65. Doupis J. Lyons T.E. Wu S. Gnardellis C. Dinh T. Veves A. Microvascular reactivity and inflammatory cytokines in painful and painless peripheral diabetic neuropathy. J. Clin. Endocrinol. Metab. 2009 94 6 2157 2163 10.1210/jc.2008‑2385 19276232
    [Google Scholar]
  66. Magrinelli F. Briani C. Romano M. Ruggero S. Toffanin E. Triolo G. Peter G.C. Praitano M. Lauriola M.F. Zanette G. Tamburin S. The association between serum cytokines and damage to large and small nerve fibers in diabetic peripheral neuropathy. J. Diabetes Res. 2015 2015 1 7 10.1155/2015/547834 25961054
    [Google Scholar]
  67. Spallonel V. Morganti R. D’Amato C. Cacciotti L. Fedele T. Maiello M.R. Marfia G. Clinical correlates of painful diabetic neuropathy and relationship of neuropathic pain with sensorimotor and autonomic nerve function. Eur. J. Pain 2011 15 2 153 160 10.1016/j.ejpain.2010.06.011 20619708
    [Google Scholar]
  68. Herder C. Kannenberg J.M. Huth C. Carstensen-Kirberg M. Rathmann W. Koenig W. Heier M. Püttgen S. Thorand B. Peters A. Roden M. Meisinger C. Ziegler D. Proinflammatory cytokines predict the incidence and progression of distal sensorimotor polyneuropathy: KORA F4/FF4 study. Diabetes Care 2017 40 4 569 576 10.2337/dc16‑2259 28174259
    [Google Scholar]
  69. Herder C. de las Heras Gala T. Carstensen-Kirberg M. Huth C. Zierer A. Wahl S. Sudduth-Klinger J. Kuulasmaa K. Peretz D. Ligthart S. Bongaerts B.W.C. Dehghan A. Ikram M.A. Jula A. Kee F. Pietilä A. Saarela O. Zeller T. Blankenberg S. Meisinger C. Peters A. Roden M. Salomaa V. Koenig W. Thorand B. Circulating levels of interleukin 1-receptor antagonist and risk of cardiovascular disease: Meta-analysis of six population-based cohorts. Arterioscler. Thromb. Vasc. Biol. 2017 37 6 1222 1227 10.1161/ATVBAHA.117.309307 28428221
    [Google Scholar]
  70. Perkins B.A. Lovblom L.E. Bril V. Scarr D. Ostrovski I. Orszag A. Edwards K. Pritchard N. Russell A. Dehghani C. Pacaud D. Romanchuk K. Mah J.K. Jeziorska M. Marshall A. Shtein R.M. Pop-Busui R. Lentz S.I. Boulton A.J.M. Tavakoli M. Efron N. Malik R.A. Corneal confocal microscopy for identification of diabetic sensorimotor polyneuropathy: A pooled multinational consortium study. Diabetologia 2018 61 8 1856 1861 10.1007/s00125‑018‑4653‑8 29869146
    [Google Scholar]
  71. Ban J. Pan X. Yang L. Jia Z. Zhen R. Zhang X. Chen S. Correlation between fibrinogen/albumin and diabetic peripheral neuropathy. Diabetes Metab. Syndr. Obes. 2023 16 2991 3005 10.2147/DMSO.S427510 37790261
    [Google Scholar]
  72. Papachristou S. Pafili K. Papanas N. Skin AGEs and diabetic neuropathy. BMC Endocr. Disord. 2021 21 1 28 10.1186/s12902‑021‑00697‑7 33622304
    [Google Scholar]
  73. Xue T. Zhang X. Xing Y. Liu S. Zhang L. Wang X. Yu M. Advances about immunoinflammatory pathogenesis and treatment in diabetic peripheral neuropathy. Front. Pharmacol. 2021 12 748193 10.3389/fphar.2021.748193 34671261
    [Google Scholar]
  74. Burgess J. Frank B. Marshall A. Khalil R.S. Ponirakis G. Petropoulos I.N. Cuthbertson D.J. Malik R.A. Alam U. Early detection of diabetic peripheral neuropathy: A focus on small nerve fibres. Diagnostics 2021 11 2 165 10.3390/diagnostics11020165 33498918
    [Google Scholar]
  75. Ardeleanu V. Toma A. Pafili K. Papanas N. Motofei I. Diaconu C.C. Rizzo M. Pantea Stoian A. Current pharmacological treatment of painful diabetic neuropathy: A narrative review. Medicina 2020 56 1 25 10.3390/medicina56010025 31936646
    [Google Scholar]
  76. Gonz’alez-Clemente J.M. Mauricio D. Richart C. Broch M. Caixas A. Megia A. Diabetic neuropathy is associated with activation of the TNF-a system in subjects with type 1 diabetes mellitus. Clin. Endocrinol. 2005 63 5 525 529 10.1111/j.1365‑2265.2005.02376.x 16268804
    [Google Scholar]
  77. Di Iorio A. Cherubini A. Volpato S. Sparvieri E. Lauretani F. Franceschi C. Senin U. Abate G. Paganelli R. Martin A. Andres-Lacueva C. Ferrucci L. Markers of inflammation, Vitamin E and peripheral nervous system function. Neurobiol. Aging 2006 27 9 1280 1288 10.1016/j.neurobiolaging.2005.07.004 16112778
    [Google Scholar]
  78. Jin H.Y. Park T.S. Role of inflammatory biomarkers in diabetic peripheral neuropathy. J. Diabetes Investig. 2018 9 5 1016 1018 10.1111/jdi.12794 29277966
    [Google Scholar]
  79. Herder C. Lankisch M. Ziegler D. Rathmann W. Koenig W. Illig T. Döring A. Thorand B. Holle R. Giani G. Martin S. Meisinger C. Subclinical inflammation and diabetic polyneuropathy: MONICA/KORA Survey F3 (Augsburg, Germany). Diabetes Care 2009 32 4 680 682 10.2337/dc08‑2011 19131463
    [Google Scholar]
  80. Nybo M. Poulsen M.K. Grauslund J. Henriksen J.E. Rasmussen L.M. Plasma osteoprotegerin concentrations in peripheral sensory neuropathy in Type 1 and Type 2 diabetic patients. Diabet. Med. 2010 27 3 289 294 10.1111/j.1464‑5491.2010.02940.x 20536491
    [Google Scholar]
  81. Herder C. Bongaerts B.W.C. Rathmann W. Heier M. Kowall B. Koenig W. Thorand B. Roden M. Meisinger C. Ziegler D. Association of subclinical inflammation with polyneuropathy in the older population: KORA F4 study. Diabetes Care 2013 36 11 3663 3670 10.2337/dc13‑0382 24009302
    [Google Scholar]
  82. Jung C.H. Kim B.Y. Mok J.O. Kang S.K. Kim C.H. Association between serum adipocytokine levels and microangiopathies in patients with type 2 diabetes mellitus. J. Diabetes Investig. 2014 5 3 333 339 10.1111/jdi.12144 24843783
    [Google Scholar]
  83. Herder C. Bongaerts B.W.C. Ouwens D.M. Rathmann W. Heier M. Carstensen-Kirberg M. Koenig W. Thorand B. Roden M. Meisinger C. Ziegler D. Low serum omentin levels in the elderly population with Type 2 diabetes and polyneuropathy. Diabet. Med. 2015 32 11 1479 1483 10.1111/dme.12761 26094489
    [Google Scholar]
  84. Herder C. Bongaerts B.W.C. Rathmann W. Heier M. Kowall B. Koenig W. Thorand B. Roden M. Meisinger C. Ziegler D. Differential association between biomarkers of subclinical inflammation and painful polyneuropathy: Results from the KORA F4 study. Diabetes Care 2015 38 1 91 96 10.2337/dc14‑1403 25325880
    [Google Scholar]
  85. Schamarek I. Herder C. Nowotny B. Carstensen-Kirberg M. Straßburger K. Nowotny P. Strom A. Püttgen S. Müssig K. Szendroedi J. Roden M. Ziegler D. Adiponectin, markers of subclinical inflammation and nerve conduction in individuals with recently diagnosed type 1 and type 2 diabetes. Eur. J. Endocrinol. 2016 174 4 433 443 10.1530/EJE‑15‑1010 26733478
    [Google Scholar]
  86. Schlesinger S. Herder C. Kannenberg J.M. Huth C. Carstensen-Kirberg M. Rathmann W. Bönhof G.J. Koenig W. Heier M. Peters A. Meisinger C. Roden M. Thorand B. Ziegler D. General and abdominal obesity and incident distal sensorimotor polyneuropathy: Insights into inflammatory biomarkers as potential mediators in the KORA F4/FF4 cohort. Diabetes Care 2019 42 2 240 247 10.2337/dc18‑1842 30523031
    [Google Scholar]
  87. Liu S. Zheng H. Zhu X. Mao F. Zhang S. Shi H. Li Y. Lu B. Neutrophil-to-lymphocyte ratio is associated with diabetic peripheral neuropathy in type 2 diabetes patients. Diabetes Res. Clin. Pract. 2017 130 90 97 10.1016/j.diabres.2017.05.008 28582723
    [Google Scholar]
  88. Xu T. Weng Z. Pei C. Yu S. Chen Y. Guo W. Wang X. Luo P. Sun J. The relationship between neutrophil-to-lymphocyte ratio and diabetic peripheral neuropathy in Type 2 diabetes mellitus. Medicine 2017 96 45 e8289 10.1097/MD.0000000000008289 29137012
    [Google Scholar]
  89. Herder C. Kannenberg J.M. Carstensen-Kirberg M. Strom A. Bönhof G.J. Rathmann W. Huth C. Koenig W. Heier M. Krumsiek J. Peters A. Meisinger C. Roden M. Thorand B. Ziegler D. A systemic inflammatory signature reflecting cross talk between innate and adaptive immunity is associated with incident polyneuropathy: KORA F4/FF4 study. Diabetes 2018 67 11 2434 2442 10.2337/db18‑0060 30115651
    [Google Scholar]
  90. Jude E.B. Abbott C.A. Young M.J. Anderson S.G. Douglas J.T. Boulton A.J.M. The potential role of cell adhesion molecules in the pathogenesis of diabetic neuropathy. Diabetologia 1998 41 3 330 336 10.1007/s001250050911 9541174
    [Google Scholar]
  91. Roustit M. Loader J. Deusenbery C. Baltzis D. Veves A. Endothelial dysfunction as a link between cardiovascular risk factors and peripheral neuropathy in diabetes. J. Clin. Endocrinol. Metab. 2016 101 9 3401 3408 10.1210/jc.2016‑2030 27399351
    [Google Scholar]
  92. Gruden G. Bruno G. Chaturvedi N. Burt D. Schalkwijk C. Pinach S. Stehouwer C.D. Witte D.R. Fuller J.H. Perin P.C. Serum heat shock protein 27 and diabetes complications in the EURODIAB prospective complications study: A novel circulating marker for diabetic neuropathy. Diabetes 2008 57 7 1966 1970 10.2337/db08‑0009 18390793
    [Google Scholar]
  93. Pourhamidi K. Dahlin L.B. Boman K. Rolandsson O. Heat shock protein 27 is associated with better nerve function and fewer signs of neuropathy. Diabetologia 2011 54 12 3143 3149 10.1007/s00125‑011‑2303‑5 21909836
    [Google Scholar]
  94. Elsharkawy R.E. Abdel Azim G.S. Osman M.A. Maghraby H.M. Mohamed R.A. Abdelsalam E.M. Ebrahem E.E. Seliem N.M.A. Peripheral polyneuropathy and cognitive impairment in Type II diabetes mellitus. Neuropsychiatr. Dis. Treat. 2021 17 627 635 10.2147/NDT.S284308 33658784
    [Google Scholar]
  95. Hu Y. Liu F. Shen J. Zeng H. Li L. Zhao J. Zhao J. Lu F. Jia W. Association between serum cystatin C and diabetic peripheral neuropathy: A cross-sectional study of a Chinese type 2 diabetic population. Eur. J. Endocrinol. 2014 171 5 641 648 10.1530/EJE‑14‑0381 25184282
    [Google Scholar]
  96. Kottaisamy C.P.D. Raj D.S. Prasanth Kumar V. Sankaran U. Experimental animal models for diabetes and its related complications—A review. Lab. Anim. Res. 2021 37 1 23 10.1186/s42826‑021‑00101‑4 34429169
    [Google Scholar]
  97. Brell J.M. Animal models of peripheral neuropathy: Modeling what we feel, understanding what they feel. ILAR J. 2014 54 3 253 258 10.1093/ilar/ilt056 24615438
    [Google Scholar]
  98. Thomas P.K. Diabetic neuropathy: Models, mechanisms and mayhem. Can. J. Neurol. Sci. 1992 19 1 1 7 10.1017/S0317167100042463 1562904
    [Google Scholar]
  99. Gao F. Zheng Z. Animal models of diabetic neuropathic pain. Exp. Clin. Endocrinol. Diabetes 2014 122 2 100 106 10.1055/s‑0033‑1363234 24554509
    [Google Scholar]
  100. Höke A. Animal models of peripheral neuropathies. Neurotherapeutics 2012 9 2 262 269 10.1007/s13311‑012‑0116‑y 22415319
    [Google Scholar]
  101. Calcutt N.A. Freshwater J.D. Mizisin A.P. Prevention of sensory disorders in diabetic Sprague-Dawley rats by aldose reductase inhibition or treatment with ciliary neurotrophic factor. Diabetologia 2004 47 4 718 724 10.1007/s00125‑004‑1354‑2 15298349
    [Google Scholar]
  102. Somani R.S. Shaikh A.S. Animal models and biomarkers of neuropathy in diabetic rodents. Indian J. Pharmacol. 2010 42 3 129 134 10.4103/0253‑7613.66833 20871761
    [Google Scholar]
  103. Freshwater J.D. Calcutt N.A. Low doses of formalin reveal allodynia in diabetic rats. J. Neuropathic Pain Symptom Palliation 2005 1 1 39 46 10.3109/J426v01n01_08
    [Google Scholar]
  104. Cameron N.E. Cotter M.A. Jack A.M. Basso M.D. Hohman T.C. Protein kinase C effects on nerve function, perfusion, Na +, K + -ATPase activity and glutathione content in diabetic rats. Diabetologia 1999 42 9 1120 1130 10.1007/s001250051280 10447525
    [Google Scholar]
  105. Cameron N.E. Cotter M.A. Archibald V. Dines K.C. Maxfield E.K. Anti-oxidant and pro-oxidant effects on nerve conduction velocity, endoneurial blood flow and oxygen tension in non-diabetic and streptozotocin-diabetic rats. Diabetologia 1994 37 5 449 459 10.1007/s001250050131 8056181
    [Google Scholar]
  106. Garcia Soriano F. Virág L. Jagtap P. Szabó É. Mabley J.G. Liaudet L. Marton A. Hoyt D.G. Murthy K.G.K. Salzman A.L. Southan G.J. Szabó C. Diabetic endothelial dysfunction: The role of poly(ADP-ribose) polymerase activation. Nat. Med. 2001 7 1 108 113 10.1038/83241 11135624
    [Google Scholar]
  107. Kong M.F. Horowitz M. Jones K.L. Wishart J.M. Harding P.E. Natural history of diabetic gastroparesis. Diabetes Care 1999 22 3 503 507 10.2337/diacare.22.3.503 10097936
    [Google Scholar]
  108. Karanth S.S. Springall D.R. Francavilla S. Mirrlees D.J. Polak J.M. Early increase in CGRP- and VIP-immunoreactive nerves in the skin of streptozotocin-induced diabetic rats. Histochemistry 1990 94 6 659 666 10.1007/BF00271994 1704001
    [Google Scholar]
  109. Chen Y.S. Chung S.S.M. Chung S.K. Noninvasive monitoring of diabetes-induced cutaneous nerve fiber loss and hypoalgesia in thy1-YFP transgenic mice. Diabetes 2005 54 11 3112 3118 10.2337/diabetes.54.11.3112 16249433
    [Google Scholar]
  110. Sango K. Mizukami H. Horie H. Yagihashi S. Impaired axonal regeneration in diabetes. Perspective on the underlying mechanism from in vivo and in vitro experimental studies. Front. Endocrinol. 2017 8 12 10.3389/fendo.2017.00012 28203223
    [Google Scholar]
  111. Kellogg A.P. Wiggin T.D. Larkin D.D. Hayes J.M. Stevens M.J. Pop-Busui R. Protective effects of cyclooxygenase-2 gene inactivation against peripheral nerve dysfunction and intraepidermal nerve fiber loss in experimental diabetes. Diabetes 2007 56 12 2997 3005 10.2337/db07‑0740 17720896
    [Google Scholar]
  112. Goldfine A.B. Silver R. Aldhahi W. Cai D. Tatro E. Lee J. Shoelson S.E. Use of salsalate to target inflammation in the treatment of insulin resistance and type 2 diabetes. Clin. Transl. Sci. 2008 1 1 36 43 10.1111/j.1752‑8062.2008.00026.x 19337387
    [Google Scholar]
  113. Cameron N. Cotter M. Pro-inflammatory mechanisms in diabetic neuropathy: Focus on the nuclear factor kappa B pathway. Curr. Drug Targets 2008 9 1 60 67 10.2174/138945008783431718 18220713
    [Google Scholar]
  114. Hotamisligil G.S. Inflammation and metabolic disorders. Nature 2006 444 7121 860 867 10.1038/nature05485 17167474
    [Google Scholar]
  115. Goldberg R.B. Cytokine and cytokine-like inflammation markers, endothelial dysfunction, and imbalanced coagulation in development of diabetes and its complications. J. Clin. Endocrinol. Metab. 2009 94 9 3171 3182 10.1210/jc.2008‑2534 19509100
    [Google Scholar]
  116. Libby P. Ridker P.M. Maseri A. Inflammation and atherosclerosis. Circulation 2002 105 9 1135 1143 10.1161/hc0902.104353 11877368
    [Google Scholar]
  117. Mora C. Navarro J.F. Inflammation and diabetic nephropathy. Curr. Diab. Rep. 2006 6 6 463 468 10.1007/s11892‑006‑0080‑1 17118230
    [Google Scholar]
  118. Lopes-Virella M.F. Carter R.E. Gilbert G.E. Klein R.L. Jaffa M. Jenkins A.J. Lyons T.J. Garvey W.T. Virella G. Risk factors related to inflammation and endothelial dysfunction in the DCCT/EDIC cohort and their relationship with nephropathy and macrovascular complications. Diabetes Care 2008 31 10 2006 2012 10.2337/dc08‑0659 18628568
    [Google Scholar]
  119. Tabur S. Korkmaz H. Ozkaya M. Aksoy S.N. Akarsu E. Is calprotectin a novel biomarker of neuroinflammation in diabetic periferal neuropathy? Diabetol. Metab. Syndr. 2015 7 1 36 10.1186/s13098‑015‑0030‑7 25995771
    [Google Scholar]
  120. Boenhof GJ Strom A Rathmann W Heier M Meisinger C Peters A Roden M Thorand B Herder C Ziegler D Differential association of inflammatory markers and growth factors with type 2 diabetes and polyneuropathy—a multimarker approach. Diabetes 2018 67 Supplement_1 63-OR 10.2337/db18‑63‑OR
    [Google Scholar]
  121. Pradhan A.D. Manson J.E. Rifai N. Buring J.E. Ridker P.M. C-reactive protein, interleukin 6, and risk of developing type 2 diabetes mellitus. JAMA 2001 286 3 327 334 10.1001/jama.286.3.327 11466099
    [Google Scholar]
  122. Schmidt M.I. Duncan B.B. Sharrett A.R. Lindberg G. Savage P.J. Offenbacher S. Azambuja M.I. Tracy R.P. Heiss G. Markers of inflammation and prediction of diabetes mellitus in adults (Atherosclerosis Risk in Communities study): A cohort study. Lancet 1999 353 9165 1649 1652 10.1016/S0140‑6736(99)01046‑6 10335783
    [Google Scholar]
/content/journals/cnsamc/10.2174/0118715249358465250522173332
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The Role of Novel Biomarkers in the Early Management of Peripheral Diabetic Neuropathy
Bentham Science Publishers ; https://doi.org/10.2174/0118715249358465250522173332
/content/journals/cnsamc/10.2174/0118715249358465250522173332
/content/journals/cnsamc/10.2174/0118715249358465250522173332
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  • Article Type:     Review Article
Keywords: molecular mechanism ; Novel biomarker ; pathology ; diabetic neuropathy

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