Diabetic peripheral neuropathy (DPN) is one of the common chronic complications of diabetes, which seriously affects the life quality of diabetic patients. Therefore, early clinical diagnosis is very important for the prevention and treatment of DPN. Hyperuricemia is a metabolic disease caused by purine nucleotide metabolism disorder. Although a large number of studies have shown that the hyperuricemia may be an independent risk factor for DPN, its potential effects on DPN and mechanisms of action have not been fully elucidated. This paper summarizes the pathogenesis of DPN, introduces the role of uric acid in the pathogenesis of DPN, and expounds that oxidative stress and inflammation are the roles of hyperuricemia in the pathogenesis of DPN, so as to provide references for finding early clinical warning indicators.

1.Liu R，Han C，Wu D，et al. Prevalence of hyperuricemia and gout in mainland China from 2000 to 2014: a systematic review and Meta-analysis[J]. Biomed Res Int，2015, 2015: 762820. DOI: 10.1155/2015/762820.

2.Jiang J, Zhang T, Liu Y, et al. Prevalence of diabetes in patients with hyperuricemia and gout: a systematic review and Meta-analysis[J]. Curr Diab Rep, 2023, 23(6): 103-117. DOI: 10.1007/s11892-023-01506-2.

3.Hu X, Rong S, Wang Q, et al. Association between plasma uric acid and insulin resistance in type 2 diabetes: a mendelian randomization analysis[J]. Diabetes Res Clin Pract, 2021, 171: 108542. DOI: 10.1016/j.diabres.2020.108542.

4.Jia Z, Zhang X, Kang S, et al. Serum uric acid levels and incidence of impaired fasting glucose and type 2 diabetes mellitus: a Meta-analysis of cohort studies[J]. Diabetes Res Clin Pract, 2013, 101(1): 88-96. DOI: 10.1016/j.diabres.2013.03.026.

5.Wang Y, Shao T,Wang J, et al. An update on potential biomarkers for diagnosing diabetic foot ulcer at early stage[J]. Biomed Pharmacother, 2021, 133: 110991. DOI: 10.1016/j.biopha.2020.110991.

6.Pop-Busui R, Boulton AJM, Feldman EL, et al. Diabetic neuropathy: a position statement by the american diabetes association[J]. Diabetes Care, 2017, 40(1): 136-154. DOI: 10.2337/dc16-2042.

7.Cernea S, Raz I. Management of diabetic neuropathy[J]. Metabolism, 2021, 123: 154867. DOI: 10.1016/j.metabol.2021.154867.

8.Sloan G, Selvarajah D, Tesfaye S. Pathogenesis, diagnosis and clinical management of diabetic sensorimotor peripheral neuropathy[J]. Nat Rev Endocrinol, 2021, 17(7): 400-420. DOI: 10.1038/s41574-021-00496-z.

9.Feldman EL, Callaghan BC, Pop-Busui R, et al. Diabetic neuropathy[J]. Nat Rev Dis Primers, 2019, 5(1): 41. DOI: 10.1038/s41572-019-0092-1.

10.Feldman EL, Nave KA, Jensen TS, et al. New horizons in diabetic neuropathy: mechanisms, bioenergetics, and pain[J]. Neuron, 2017, 93(6): 1296-1313. DOI: 10.1016/j.neuron.2017.02.005.

11.Fernyhough P, McGavock J. Mechanisms of disease: mitochondrial dysfunction in sensory neuropathy and other complications in diabetes[J]. Handb Clin Neurol, 2014, 126: 353-377. DOI: 10.1016/B978-0-444-53480-4.00027-8.

12.Kimura Y, Tsukui D, Kono H. Uric acid in inflammation and the pathogenesis of atherosclerosis[J]. Int J Mol Sci, 2021, 22(22): 12394. DOI: 10.3390/ijms222212394.

13.Liu N, Xu H, Sun Q, et al. The role of oxidative stress in hyperuricemia and xanthine oxidoreductase (XOR) inhibitors[J]. Oxid Med Cell Longev, 2021, 2021: 1-15. DOI: 10.1155/2021/1470380.

14.Gherghina ME, Peride I, Tiglis M, et al. Uric acid and oxidative stress—relationship with cardiovascular, metabolic, and renal impairment[J]. Int J Mol Sci, 2022, 23(6): 3188. DOI: 10.3390/ijms23063188.

15.Jakše B, Jakše B, Pajek M, et al. Uric acid and plant-based nutrition[J]. Nutrients, 2019, 11(8): 1736. DOI: 10.3390/nu11081736.

16.Glantzounis G, Tsimoyiannis E, Kappas A, et al. Uric acid and oxidative stress[J]. Curr Pharm Des, 2005, 11(32): 4145-4151. DOI: 10.2174/138161205774913255.

17.Muraoka S, Miura T. Inhibition by uric acid of free radicals that damage biological molecules[J]. Pharmacol Toxicol, 2003, 93(6): 284-289. DOI: 10.1111/j.1600-0773.2003.pto930606.x.

18.Kang DH, Ha SK. Uric acid puzzle: dual role as anti-oxidantand pro-oxidant[J]. Electrolyte Blood Press, 2014, 12(1): 1-6. DOI: 10.5049/ebp.2014.12.1.1.

19.Li L, Zhang Y, Zeng C. Update on the epidemiology, genetics, and therapeutic options of hyperuricemia[J]. Am J Transl Res, 2020, 12(7): 3167-3181. https://pubmed.ncbi.nlm.nih.gov/32774692/.

20.Oyenihi AB, Ayeleso AO, Mukwevho E, et al. Antioxidant strategies in the management of diabetic neuropathy[J]. Biomed Res Int, 2015, 2015: 1-15. DOI: 10.1155/2015/515042.

21.Gherghina ME, Peride I, Tiglis M, et al. Uric acid and oxidative stress-relationship with cardiovascular, metabolic, and renal impairment[J]. Int J Mol Sci, 2022, 23(6): 3188. DOI: 10.3390/ijms23063188.

22.Shields HJ, Traa A, Van Raamsdonk JM. Beneficial and detrimental effects of reactive oxygen species on lifespan: a comprehensive review of comparative and experimental studies[J]. Front Cell Dev Biol, 2021, 9: 628157. DOI: 10.3389/fcell.2021.628157.

23.Méndez-Morales ST, Pérez-De Marcos JC, Rodríguez-Cortés O, et al. Diabetic neuropathy: molecular approach a treatment opportunity[J]. Vascul Pharmacol, 2022, 143: 106954. DOI: 10.1016/j.vph.2022.106954.

24.Pang L, Lian X, Liu H, et al. Understanding diabetic neuropathy: focus on oxidative stress[J]. Oxid Med Cell Longev, 2020, 2020: 9524635. DOI: 10.1155/2020/9524635.

25.Magnoni M, Berteotti M, Ceriotti F, et al. Serum uric acid on admission predicts in-hospital mortality in patients with acute coronary syndrome[J]. Int J Cardiol, 2017, 240: 25-29. DOI: 10.1016/j.ijcard.2017.04.027.

26.Su HY, Yang C, Liang D, et al. Research advances in the mechanisms of hyperuricemia-induced renal injury[J]. Biomed Res Int, 2020, 2020: 1-12. DOI: 10.1155/2020/5817348.

27.Fan DF, Han XC,Ye ZH, et al. Hydrogen exerts neuroprotective effects by inhibiting oxidative stress in experimental diabetic peripheral neuropathy rats[J]. Med Gas Res, 2023, 13(2): 72-77. DOI: 10.4103/2045-9912.345171.

28.Papežíková I, Pekarová M, Kolářová H, et al. Uric acid modulates vascular endothelial function through the down regulation of nitric oxide production[J]. Free Radic Res, 2012, 47(2): 82-88. DOI: 10.3109/10715762.2012.747677.

29.Copur S, Demiray A, Kanbay M. Uric acid in metabolic syndrome: does uric acid have a definitive role?[J]. Eur J Intern Med, 2022, 103: 4-12. DOI: 10.1016/j.ejim.2022.04.022.

30.Agrawal NK, Kant S. Targeting inflammation in diabetes: newer therapeutic options[J]. World J Diabetes, 2014, 5(5): 697-710. DOI: 10.4239/wjd.v5.i5.697.

31.Feng Y, Chen L, Luo Q, et al. Involvement of microRNA-146a in diabetic peripheral neuropathy through the regulation of inflammation[J]. Drug Des Devel Ther, 2018, 12: 171-177. DOI: 10.2147/dddt.S157109.

32.Skundric DS, Lisak RP. Role of neuropoietic cytokines in development and progression of diabetic polyneuropathy: from glucose metabolism to neurodegeneration[J]. Exp Diabesity Res, 2003, 4(4): 303-312. DOI: 10.1155/edr.2003.303.

33.Mu ZP, Wang YG, Li CQ, et al. Association between tumor necrosis factor-α and diabetic peripheral neuropathy in patients with type 2 diabetes: a Meta-analysis[J]. Mol Neurobiol, 2017, 54(2): 983-996. DOI: 10.1007/s12035-016-9702-z.

34.Johnson RJ, Bakris GL, Borghi C, et al. Hyperuricemia, acute and chronic kidney disease, hypertension, and cardiovascular disease: report of a scientific workshop organized by the national kidney foundation[J]. Am J Kidney Dis, 2018, 71(6): 851-865. DOI: 10.1053/j.ajkd.2017.12.009.

35.Yu W, Cheng JD. Uric acid and cardiovascular disease: an update from molecular mechanism to clinical perspective[J]. Front Pharmacol, 2020, 11: 582680. DOI: 10.3389/fphar.2020.582680.

36.Zhao Y, Qian Y, Sun Z, et al. Role of PI3K in the progression and regression of atherosclerosis[J]. Front Pharmacol, 2021, 12: 632378. DOI: 10.3389/fphar.2021.632378.

37.Sanchez-Lozada LG, Rodriguez-Iturbe B, Kelley EE, et al. Uric acid and hypertension: an update with recommendations[J]. Am J Hypertens, 2020, 33(7): 583-594. DOI: 10.1093/ajh/hpaa044.

38.Joosten LAB, Crişan TO, Bjornstad P, et al. Asymptomatic hyperuricaemia: a silent activator of the innate immune system[J]. Nat Rev Rheumatol, 2019, 16(2): 75-86. DOI: 10.1038/s41584-019-0334-3.

39.Jiang TN, Li YF, Huo LL, et al. Association between serum uric acid and large-nerve fiber dysfunction in type 2 diabetes[J]. Chin Med J (Engl), 2019, 132(9): 1015-1022. DOI: 10.1097/cm9.0000000000000223.

40.Fayazi HS, Yaseri M, Mortazavi SS, et al. The relation between serum uric acid levels and diabetic peripheral neuropathy in type 2 diabetes in Guilan, north of Iran[J]. BMC Endocr Disord, 2022, 22(1): 39. DOI: 10.1186/s12902-022-00952-5.

41.Kaewput W, Thongprayoon C, Rangsin R, et al. The association between serum uric acid and peripheral neuropathy in patients with type 2 diabetes mellitus: a multicenter nationwide crosssectional study[J]. Korean J Fam Med, 2020, 41(3): 189-194. DOI: 10.4082/kjfm.18.0205.

42.Lin X, Xu L, Zhao D, et al. Correlation between serum uric acid and diabetic peripheral neuropathy in T2DM patients[J]. J Neuro Sci, 2018, 385: 78-82. DOI: 10.1016/j.jns.2017.11.034.

43.Hu Y, Li Q, Min R, et al. The association between serum uric acid and diabetic complications in patients with type 2 diabetes mellitus by gender: a cross-sectional study[J]. PeerJ, 2021, 9:e10691. DOI: 10.7717/peerj.10691.

44.Katsiki N, Dimitriadis GD, Mikhailidis DP. Serum uric acid and diabetes: from pathophysiology to cardiovascular disease[J]. Curr Pharm Des, 2021, 27(16): 1941-1951. DOI: 10.2174/1381612827666210104124320.

45.Takahashi K, Mizukami H, Osonoi S, et al. Inhibitory effects of xanthine oxidase inhibitor, topiroxostat, on development of neuropathy in db/db mice[J]. Neurobiol Dis, 2021, 155: 105392. DOI: 10.1016/j.nbd.2021.105392.

46.Zong Q, Ma G, Wang T. Uric acid lowering improves insulin sensitivity and lowers blood pressure: a Meta-analysis of randomized parallel-controlled clinical trials[J]. Afr Health Sci, 2021, 21(1): 82-95. DOI: 10.4314/ahs.v21i1.13.