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Serum Uric Acid Levels and Diabetic Peripheral Neuropathy in Type 2 Diabetes: a Systematic Review and Meta-analysis

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Abstract

Previous studies suggested a possible association between serum uric acid levels and peripheral neuropathy in patients with type 2 diabetes, but no definite evidence was available. A systematic review and meta-analysis of relevant studies were performed to comprehensively estimate the association. Pubmed, Web of Science, Embase, and China Biology Medicine (CBM) databases were searched for eligible studies. Study-specific data were combined using random-effect or fixed-effect models of meta-analysis according to between-study heterogeneity. Twelve studies were finally included into the meta-analysis, which involved a total of 1388 type 2 diabetic patients with peripheral neuropathy and 4746 patients without peripheral neuropathy. Meta-analysis showed that there were obvious increased serum uric acid levels in diabetic patients with peripheral neuropathy (weighted mean difference [WMD] = 50.03 μmol/L, 95 % confidence interval [95%CI] 22.14–77.93, P = 0.0004). Hyperuricemia was also significantly associated with increased risk of peripheral neuropathy in patients with type 2 diabetes (risk ratio [RR] = 2.83, 95%CI 2.13–3.76, P < 0.00001). Meta-analysis of two studies with adjusted risk estimates showed that hyperuricemia was independently associated with increased risk of peripheral neuropathy in type 2 diabetic patients (RR = 1.95, 95%CI 1.23–3.11, P = 0.005). Type 2 diabetic patients with peripheral neuropathy have obvious increased serum uric acid levels, and hyperuricemia is associated with increased risk of peripheral neuropathy. Further prospective cohort studies are needed to validate the impact of serum uric acid levels on peripheral neuropathy risk.

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References

  1. Callaghan BC, Cheng HT, Stables CL, Smith AL, Feldman EL (2012) Diabetic neuropathy: clinical manifestations and current treatments. Lancet Neurol 11(6):521–534

    Article  PubMed Central  PubMed  Google Scholar 

  2. Tesfaye S, Selvarajah D (2012) Advances in the epidemiology, pathogenesis and management of diabetic peripheral neuropathy. Diabetes Metab Res Rev 28 Suppl :18–14

  3. Smith SC, Lamping DL, Maclaine GD (2012) Measuring health-related quality of life in diabetic peripheral neuropathy: a systematic review. Diabetes Res Clin Pract 96(3):261–270

    Article  CAS  PubMed  Google Scholar 

  4. Monteiro-Soares M, Vaz-Carneiro A, Sampaio S, Dinis-Ribeiro M (2012) Validation and comparison of currently available stratification systems for patients with diabetes by risk of foot ulcer development. Eur J Endocrinol 167(3):401–407

    Article  CAS  PubMed  Google Scholar 

  5. Xu Y, Zhu J, Gao L, Liu Y, Shen J, Shen C, Matfin G, Wu X (2013) Hyperuricemia as an independent predictor of vascular complications and mortality in type 2 diabetes patients: a meta-analysis. PLoS One 8(10):e78206

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  6. Han T, Bai J, Liu W, Hu Y (2012) A systematic review and meta-analysis of alpha-lipoic acid in the treatment of diabetic peripheral neuropathy. Eur J Endocrinol 167(4):465–471

    Article  CAS  PubMed  Google Scholar 

  7. Gonzalez R, Pedro T, Martinez-Hervas S, Civera M, Priego MA, Catala M, Chaves FJ, Ascaso JF, Carmena R, Real JT (2012) Plasma homocysteine levels are independently associated with the severity of peripheral polyneuropathy in type 2 diabetic subjects. J Peripher Nerv Syst 17(2):191–196

    Article  CAS  PubMed  Google Scholar 

  8. Abbott CA, Malik RA, van Ross ER, Kulkarni J, Boulton AJ (2011) Prevalence and characteristics of painful diabetic neuropathy in a large community-based diabetic population in the U.K. Diabetes Care 34(10):2220–2224

    Article  PubMed Central  PubMed  Google Scholar 

  9. Martinon F (2010) Mechanisms of uric acid crystal-mediated autoinflammation. Immunol Rev 233(1):218–232

    Article  CAS  PubMed  Google Scholar 

  10. Li C, Hsieh MC, Chang SJ (2013) Metabolic syndrome, diabetes, and hyperuricemia. Curr Opin Rheumatol 25(2):210–216

    Article  CAS  PubMed  Google Scholar 

  11. Johnson RJ, Nakagawa T, Sanchez-Lozada LG, Shafiu M, Sundaram S, Le M, Ishimoto T, Sautin YY, Lanaspa MA (2013) Sugar, uric acid, and the etiology of diabetes and obesity. Diabetes 62(10):3307–3315

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  12. Hoeldtke RD, Bryner KD, McNeill DR, Hobbs GR, Riggs JE, Warehime SS, Christie I, Ganser G, Van Dyke K (2002) Nitrosative stress, uric acid, and peripheral nerve function in early type 1 diabetes. Diabetes 51(9):2817–2825

    Article  CAS  PubMed  Google Scholar 

  13. Kim SY, Guevara JP, Kim KM, Choi HK, Heitjan DF, Albert DA (2010) Hyperuricemia and coronary heart disease: a systematic review and meta-analysis. Arthritis Care Res (Hoboken) 62(2):170–180

    Google Scholar 

  14. Chuengsamarn S, Rattanamongkolgul S, Jirawatnotai S (2014) Association between serum uric acid level and microalbuminuria to chronic vascular complications in Thai patients with type 2 diabetes. J Diabetes Complicat 28(2):124–129

    Article  PubMed  Google Scholar 

  15. Kiani J, Habibi Z, Tajziehchi A, Moghimbeigi A, Dehghan A, Azizkhani H (2014) Association between serum uric acid level and diabetic peripheral neuropathy (a case control study). Caspian J Intern Med 5(1):17–21

    PubMed Central  PubMed  Google Scholar 

  16. Papanas N, Katsiki N, Papatheodorou K, Demetriou M, Papazoglou D, Gioka T, Maltezos E (2011) Peripheral neuropathy is associated with increased serum levels of uric acid in type 2 diabetes mellitus. Angiology 62(4):291–295

    Article  CAS  PubMed  Google Scholar 

  17. Lu B, Hu J, Wen J, Zhang Z, Zhou L, Li Y, Hu R (2013) Determination of peripheral neuropathy prevalence and associated factors in Chinese subjects with diabetes and pre-diabetes—ShangHai Diabetic neuRopathy Epidemiology and Molecular Genetics Study (SH-DREAMS). PLoS One 8(4):e61053

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  18. Tapp RJ, Shaw JE, de Courten MP, Dunstan DW, Welborn TA, Zimmet PZ (2003) Foot complications in type 2 diabetes: an Australian population-based study. Diabet Med 20(2):105–113

    Article  CAS  PubMed  Google Scholar 

  19. Wells G, Shea B, O’connell D, Peterson J, Welch V, Losos M, Tugwell P (2014) The Newcastle-Ottawa Scale (NOS) for assessing the quality of nonrandomised studies in meta-analyses. Ottawa Health Research Institute Web site

  20. Cochran WG (1954) The combination of estimates from different experiments. Biometrics 10(1):101–129

    Article  Google Scholar 

  21. Higgins JP, Thompson SG, Deeks JJ, Altman DG (2003) Measuring inconsistency in meta-analyses. BMJ 327(7414):557–560

    Article  PubMed Central  PubMed  Google Scholar 

  22. DerSimonian R, Laird N (1986) Meta-analysis in clinical trials. Control Clin Trials 7(3):177–188

    Article  CAS  PubMed  Google Scholar 

  23. Mantel N, Haenszel W (1959) Statistical aspects of the analysis of data from retrospective studies of disease. J Natl Cancer Inst 22(4):719–748

    CAS  PubMed  Google Scholar 

  24. Egger M, Davey Smith G, Schneider M, Minder C (1997) Bias in meta-analysis detected by a simple, graphical test. BMJ 315(7109):629–634

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  25. Pinto A, Tuttolomondo A, Di Raimondo D, Fernandez P, La Placa S, Di Gati M, Licata G (2008) Cardiovascular risk profile and morbidity in subjects affected by type 2 diabetes mellitus with and without diabetic foot. Metabolism 57(5):676–682

    Article  CAS  PubMed  Google Scholar 

  26. Ito H, Abe M, Mifune M, Oshikiri K, Antoku S, Takeuchi Y, Togane M (2011) Hyperuricemia is independently associated with coronary heart disease and renal dysfunction in patients with type 2 diabetes mellitus. PLoS One 6(11):e27817

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  27. Meng L, Zhu J (2008) An analysis of clinical features of accompanying periphery neuropathy in 132 cases with type 2 diabetes [article in Chinese]. J Xinjiang Med Univ 31(5):515–520

    CAS  Google Scholar 

  28. Guo L, Luo Y, Liu W, Luan J, Yang H, Chen B (2012) Level of UA and related factors in DPN patients [article in Chinese]. Anhui Med Pharma J 16(1):73–75

    CAS  Google Scholar 

  29. Sang Y (2012) Relationship between serum uric acid and microvascular complications in patients with type 2 diabetes mellitus [article in Chinese]. J Med Forum 33(8):25–26

    Google Scholar 

  30. Wang S (2012) Correlation analysis between the hyperuricemia and diabetic peripheral neuropathy [article in Chinese]. China Med Pharm 2(5):169–170

    Google Scholar 

  31. Wei X, Wu W (2012) The correlation analysis of hyperuricemia and vascular complications of type II diabetes [article in Chinese]. Med J West China 24(5):891–895

    Google Scholar 

  32. Xin S, Zhang L (2012) Correlation ship of serum uric acid with type 2 diabetic peripheral neuropathy [article in Chinese]. Clin Med 32(9):26–27

    CAS  Google Scholar 

  33. Gong L, Huang Y, Feng F (2013) Analysis of the risk factors in type 2 diabetics with hyperuricaemia [article in Chinese]. Acta Acad Med Wannan 32(4):304–306

    Google Scholar 

  34. Premkumar LS, Pabbidi RM (2013) Diabetic peripheral neuropathy: role of reactive oxygen and nitrogen species. Cell Biochem Biophys 67(2):373–383

    Article  CAS  PubMed  Google Scholar 

  35. Kim SY, Guevara JP, Kim KM, Choi HK, Heitjan DF, Albert DA (2009) Hyperuricemia and risk of stroke: a systematic review and meta-analysis. Arthritis Rheum 61(7):885–892

    Article  PubMed Central  PubMed  Google Scholar 

  36. Petta S, Camma C, Cabibi D, Di Marco V, Craxi A (2011) Hyperuricemia is associated with histological liver damage in patients with non-alcoholic fatty liver disease. Aliment Pharmacol Ther 34(7):757–766

    Article  CAS  PubMed  Google Scholar 

  37. Yang T, Chu CH, Bai CH, You SL, Chou YC, Chou WY, Chien KL, Hwang LC, Su TC, Tseng CH, Sun CA (2012) Uric acid level as a risk marker for metabolic syndrome: a Chinese cohort study. Atherosclerosis 220(2):525–531

    Article  CAS  PubMed  Google Scholar 

  38. Goncalves JP, Oliveira A, Severo M, Santos AC, Lopes C (2012) Cross-sectional and longitudinal associations between serum uric acid and metabolic syndrome. Endocrine 41(3):450–457

    Article  CAS  PubMed  Google Scholar 

  39. Choi YJ, Yoon Y, Lee KY, Hien TT, Kang KW, Kim KC, Lee J, Lee MY, Lee SM, Kang DH, Lee BH (2014) Uric acid induces endothelial dysfunction by vascular insulin resistance associated with the impairment of nitric oxide synthesis. FASEB J 28(7):3197–3204

    Article  CAS  PubMed  Google Scholar 

  40. Nagahama K, Inoue T, Iseki K, Touma T, Kinjo K, Ohya Y, Takishita S (2004) Hyperuricemia as a predictor of hypertension in a screened cohort in Okinawa, Japan. Hypertens Res 27(11):835–841

    Article  PubMed  Google Scholar 

  41. Krishnan E, Akhras KS, Sharma H, Marynchenko M, Wu EQ, Tawk R, Liu J, Shi L (2013) Relative and attributable diabetes risk associated with hyperuricemia in US veterans with gout. QJM 106(8):721–729

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  42. Papanas N, Demetriou M, Katsiki N, Papatheodorou K, Papazoglou D, Gioka T, Kotsiou S, Maltezos E, Mikhailidis DP (2011) Increased serum levels of uric acid are associated with sudomotor dysfunction in subjects with type 2 diabetes mellitus. Exp Diabetes Res 1–5

  43. Fabbrini E, Serafini M, Colic Baric I, Hazen SL, Klein S (2014) Effect of plasma uric acid on antioxidant capacity, oxidative stress, and insulin sensitivity in obese subjects. Diabetes 63(3):976–981

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  44. Stamp LK, Turner R, Khalilova IS, Zhang M, Drake J, Forbes LV, Kettle AJ (2014) Myeloperoxidase and oxidation of uric acid in gout: implications for the clinical consequences of hyperuricaemia. Rheumatology (Oxford)

  45. Johnson RJ, Kang DH, Feig D, Kivlighn S, Kanellis J, Watanabe S, Tuttle KR, Rodriguez-Iturbe B, Herrera-Acosta J, Mazzali M (2003) Is there a pathogenetic role for uric acid in hypertension and cardiovascular and renal diaease? Hypertension 41(6):1183–1190

    Article  CAS  PubMed  Google Scholar 

  46. Papezikova I, Pekarova M, Kolarova H, Klinke A, Lau D, Baldus S, Lojek A, Kubala L (2013) Uric acid modulates vascular endothelial function through the down regulation of nitric oxide production. Free Radic Res 47(2):82–88

    Article  CAS  PubMed  Google Scholar 

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    Authors and Affiliations

    1. Department of Endocrinology, Affiliated Hospital of Qingdao University, 16 Jiangsu Road, Qingdao, 266003, China

      Shuai Yu, Ying Chen, Xu Hou, Kui Che, Shengli Yan, Yangang Wang & Bin Wang

    2. Department of Rheumatology, First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, China

      Donghua Xu

    3. Essencemed Clinic, Weifang, 261000, China

      Bin Wang

    4. Shandong Provincial Key Laboratory of Metabolic Disease, Affiliated Hospital of QingdaoUniversity, Qingdao, 266003, China

      Changgui Li

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    1. Shuai Yu
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    2. Ying Chen
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    Correspondence to Yangang Wang or Bin Wang.

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    Shuai Yu, Ying Chen, and Xu Hou contributed equally to the study.

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    Yu, S., Chen, Y., Hou, X. et al. Serum Uric Acid Levels and Diabetic Peripheral Neuropathy in Type 2 Diabetes: a Systematic Review and Meta-analysis. Mol Neurobiol 53, 1045–1051 (2016). https://doi.org/10.1007/s12035-014-9075-0

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    • DOI: https://doi.org/10.1007/s12035-014-9075-0

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