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Can both normal and mildly abnormal albuminuria and glomerular filtration rate be a danger signal for diabetic peripheral neuropathy in type 2 diabetes mellitus?

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Abstract

We aimed to investigate the potential association between urinary albumin-to-creatinine ratio (UACR) and estimated glomerular filtration rate (eGFR) and diabetic peripheral neuropathy (DPN). We were especially interested in the relationship between normal or mildly abnormal UACR and eGFR with DPN. A retrospective study was performed in 1059 patients with type 2 diabetes patients from Fuzhou, China, who were seen between 2010 and 2015. The DPN population demonstrated higher UACR and lower eGFR than the non-DPN population. Nerve conduction velocities (NCVs) were negatively correlated with UACR and were positively correlated with eGFR. UACR and eGFR were associated with the risk of DPN. Even in the UACR < 30 mg/g and eGFR ≥ 60 ml/min/1.73 m2 groups, the relationship above still existed and patients in the highest tertiles of UACR and lowest tertiles of eGFR demonstrated a greater risk of DPN (OR = 2.456, 95% CI 1.461–4.127; OR = 2.021, 95% CI 1.276–3.203). Receiver operating characteristic (ROC) analysis revealed that the area under curve (AUC) of UACR, eGFR, and joints indicates that DPN was 0.749, 0.662, and 0.731, respectively. Lower eGFR and higher UACR may be associated with the risk of DPN, even though normal or mildly abnormal UACR and eGFR have already been found to be predictive factors of DPN. Further, UACR is more sensitive than eGFR. Separately, UACR was a moderate indication of DPN, and combining it with eGFR did not increase its effect of indication to DPN.

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Reference

  1. Tesfaye S, Boulton AJ, Dyck PJ, Freeman R, Horowitz M, Kempler P, Lauria G et al (2010) Toronto Diabetic Neuropathy Expert Group. Diabetic neuropathies: update on definitions, diagnostic criteria, estimation of severity, and treatments. Diabetes Care 33(10):2285–2293. doi:10.2337/dc10-1303

    Article  PubMed  PubMed Central  Google Scholar 

  2. Tesfaye S, Stevens LK, Stephenson JM, Fuller JH, Plater M, Ionescu-Tirgoviste C, Nuber A, Pozza G, Ward JD (1996) Prevalence of diabetic peripheral neuropathy and its relation to glycaemic control and potential risk factors: the EURODIAB IDDM Complications Study. Diabetologia 39(11):1377–1384

    Article  CAS  PubMed  Google Scholar 

  3. Cabezas-Cerrato J (1998) The prevalence of clinical diabetic polyneuropathy in Spain: a study in primary care and hospital clinic groups. Neuropathy Spanish Study Group of the Spanish Diabetes Society (SDS). Diabetologia 41(11):1263–1269

    Article  CAS  PubMed  Google Scholar 

  4. Cameron NE, Eaton SE, Cotter MA, Tesfaye S (2001) Vascular factors and metabolic interactions in the pathogenesis of diabetic neuropathy. Diabetologia 44(11):1973–1988. doi:10.1007/s001250100001

    Article  CAS  PubMed  Google Scholar 

  5. Brownlee M (2005) The pathobiology of diabetic complications: a unifying mechanism. Diabetes 54(6):1615–1625. doi:10.2337/diabetes.54.6.1615

    Article  CAS  PubMed  Google Scholar 

  6. Chiarelli F, Santilli F, Mohn A (2000) Role of growth factors in the development of diabetic complications. Horm Res 53(2):53–67

    CAS  PubMed  Google Scholar 

  7. Yokoyama H, Yokota Y, Tada J, Kanno S (2007) Diabetic neuropathy is closely associated with arterial stiffening and thickness in type 2 diabetes. Diabet Med 24(12):1329–1335. doi:10.1111/j.1464-5491.2007.02278.x

    Article  CAS  PubMed  Google Scholar 

  8. Brownrigg JR, de Lusignan S, McGovern A, Hughes C, Thompson MM, Ray KK, Hinchliffe RJ (2014) Peripheral neuropathy and the risk of cardiovascular events in type 2 diabetes mellitus. Heart 100(23):1837–1843. doi:10.1136/heartjnl-2014-305657

    Article  PubMed  Google Scholar 

  9. Kärvestedt L, Mårtensson E, Grill V, Elofsson S, von Wendt G, Hamsten A, Brismar K (2009) Peripheral sensory neuropathy associates with micro- or macroangiopathy: results from a population-based study of type 2 diabetic patients in Sweden. Diabetes Care 32(2):317–322. doi:10.2337/dc08-1250

    Article  PubMed  PubMed Central  Google Scholar 

  10. Edwards JL, Vincent AM, Cheng HT, Feldman EL (2008) Diabetic neuropathy: mechanisms to management. Pharmacol Ther 120(1):1–34. doi:10.1016/j.pharmthera.2008.05. 005

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Hur J, O’Brien PD, Nair V, Hinder LM, McGregor BA, Jagadish HV, Kretzler M, Brosius FC 3rd, Feldman EL (2016) Transcriptional networks of murine diabetic peripheral neuropathy and nephropathy: common and distinct gene expression patterns. Diabetologia 59(6):1297–1306. doi:10.1007/s00125-016-3913-8

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Pradeepa R, Anjana RM, Unnikrishnan R, Ganesan A, Mohan V, Rema M (2010) Risk factors for microvascular complications of diabetes among South Indian subjects with type 2 diabetes—the Chennai Urban Rural Epidemiology Study (CURES) Eye Study-5. Diabetes Technol Ther 12(10):755–761. doi:10.1089/dia.2010.0069

    Article  CAS  PubMed  Google Scholar 

  13. Parving HH, Mogensen CE, Thomas MC, Brenner BM, Cooper ME (2005) Poor prognosis in proteinuric type 2 diabetic patients with retinopathy: insights from the RENAAL study. QJM 98(2):119–126. doi:10.1093/qjmed/hci017

    Article  PubMed  Google Scholar 

  14. Tahrani AA, Dubb K, Raymond NT, Begum S, Altaf QA, Sadiqi H, Piya MK, Stevens MJ (2014) Cardiac autonomic neuropathy predicts renal function decline in patients with type 2 diabetes: a cohort study. Diabetologia 57(6):1249–1256. doi:10.1007/s00125-014-3211-2

    Article  CAS  PubMed  Google Scholar 

  15. Bell DS, Ketchum CH, Robinson CA, Wagenknecht LE, Williams BT (1992) Microalbuminuria associated with diabetic neuropathy. Diabetes Care 15(4):528–531

    Article  CAS  PubMed  Google Scholar 

  16. Hu Y, Liu F, Shen J, Zeng H, Li L, Zhao J, Zhao J, Lu F, Jia W (2014) Association between serum cystatin C and diabetic peripheral neuropathy: a cross-sectional study of a Chinese type 2 diabetic population. Eur J Endocrinol 171(5):641–648. doi:10.1530/EJE-14-0381

    Article  CAS  PubMed  Google Scholar 

  17. Yang CP, Lin CC, Li CI, Liu CS, Lin WY, Hwang KL, Yang SY, Chen HJ, Li TC (2015) Cardiovascular risk factors increase the risks of diabetic peripheral neuropathy in patients with type 2 diabetes mellitus: the Taiwan diabetes study. Medicine (Baltimore) 94(42):e1783. doi:10.1097/MD.0000000000001783

    Article  CAS  Google Scholar 

  18. American Diabetes Association (2014) Executive summary: standards of medical care in diabetes—2014. Diabetes Care 37(Suppl 1):S5–13. doi:10.2337/dc14-S005

    Google Scholar 

  19. Andrassy KM (2013) Comments on ‘KDIGO 2012 Clinical Practice Guideline for the Evaluation and Management of Chronic Kidney Disease’. Kidney Int 84(3):622–623. doi:10.1038/ki.2013.243

    Article  CAS  PubMed  Google Scholar 

  20. Tang XF, Yang T, Yang BX, Liu XZ, Rong ZP (1984) Electromyographic findings in normal Chinese. Analysis of 310 subjects. Chin Med J 97(8):613–622

    CAS  PubMed  Google Scholar 

  21. Russo GT, Giandalia A, Romeo EL, Scarcella C, Gambadoro N, Zingale R, Forte F, Perdichizzi G, Alibrandi A, Cucinotta D (2016) Diabetic neuropathy is not associated with homocysteine, folate, vitamin B12 levels, and MTHFR C677T mutation in type 2 diabetic outpatients taking metformin. J Endocrinol Investig 39(3):305–314. doi:10.1007/s40618-015-0365-9

    Article  CAS  Google Scholar 

  22. Mussap M, Dalla Vestra M, Fioretto P, Saller A, Varagnolo M, Nosadini R, Plebani M (2002) Cystatin C is a more sensitive marker than creatinine for the estimation of GFR in type 2 diabetic patients. Kidney Int 61(4):1453–1461. doi:10.1046/j.1523-1755.2002.00253.x

    Article  CAS  PubMed  Google Scholar 

  23. Smithies O (2003) Why the kidney glomerulus does not clog: a gel permeation/diffusion hypothesis of renal function. Proc Natl Acad Sci U S A 100(7):4108–4113. doi:10.1073/pnas.0730776100

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. De Cosmo S, Viazzi F, Pacilli A, Giorda C, Ceriello A, Gentile S, Russo G, Rossi MC, Nicolucci A, Guida P, Feig D, Johnson RJ, Pontremoli R (2015) AMD-Annals Study Group. Serum uric acid and risk of CKD in type 2 diabetes. Clin J Am Soc Nephrol 10(11):1921–1929. doi:10.2215/CJN.03140315

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Penno G, Solini A, Bonora E, Fondelli C, Orsi E, Zerbini G, Trevisan R, Vedovato M, Gruden G, Cavalot F, Cignarelli M, Laviola L, Morano S, Nicolucci A, Pugliese G (2011) Renal Insufficiency And Cardiovascular Events (RIACE) Study Group. Clinical significance of nonalbuminuric renal impairment in type 2 diabetes. J Hypertens 29(9):1802–1809. doi:10.1097/HJH.0b013e3283495cd6

    Article  CAS  PubMed  Google Scholar 

  26. Felsenthal G, McIvor ME (1984) Reappraisal of the electroneurographic and electromyographic diagnosis of diabetic peripheral neuropathy. Am J Phys Med 63(6):278–288

    CAS  PubMed  Google Scholar 

  27. Huang L, Yang L, Zhang S, Liu D, Yan X, Yan S (2015) Low-grade albuminuria associated with brachial-ankle pulse wave velocity in young adults with type 2 diabetes mellitus in China. Diabetes Metab Res Rev 31(3):262–268. doi:10.1002/dmrr.2598

    Article  CAS  PubMed  Google Scholar 

  28. Takase H, Sugiura T, Ohte N, Dohi Y (2015) Urinary albumin as a marker of future blood pressure and hypertension in the general population. Medicine (Baltimore) 94(6):e511. doi:10.1097/MD.0000000000000511

    Article  CAS  Google Scholar 

  29. Blecker S, Matsushita K, Köttgen A, Loehr LR, Bertoni AG, Boulware LE, Coresh J (2011) High-normal albuminuria and risk of heart failure in the community. Am J Kidney Dis 58(1):47–55. doi:10.1053/j.ajkd.2011.02.391

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Yasuda H (2009) Pathophysiology and treatment for diabetic neuropathy. Rinsho Shinkeigaku 49(4):149–157

    Article  PubMed  Google Scholar 

  31. Wada R, Yagihashi S (2005) Role of advanced glycation end products and their receptors in development of diabetic neuropathy. Ann N Y Acad Sci 1043:598–604. doi:10.1196/annals.1338.067

    Article  CAS  PubMed  Google Scholar 

  32. Kajitani N, Shikata K, Nakamura A, Nakatou T, Hiramatsu M, Makino H (2010) Microinflammation is a common risk factor for progression of nephropathy and atherosclerosis in Japanese patients with type 2 diabetes. Diabetes Res Clin Pract 88(2):171–176. doi:10.1016/j.diabres.2010.01.012

    Article  CAS  PubMed  Google Scholar 

  33. Vallance P, Collier J, Bhagat K (1997) Infection, inflammation, and infarction: does acute endothelial dysfunction provide a link. Lancet 349(9062):1391–1392. doi:10.1016/S0140-6736(96)09424-X

    Article  CAS  PubMed  Google Scholar 

  34. 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 (2011) Toronto Consensus Panel on Diabetic Neuropathy. Cardiovascular autonomic neuropathy in diabetes: clinical impact, assessment, diagnosis, and management. Diabetes Metab Res Rev 27(7):639–653. doi:10.1002/dmrr.1239

    Article  PubMed  Google Scholar 

  35. Yun JS, Ahn YB, Song KH, Yoo KD, Kim HW, Park YM, Ko SH (2015) The association between abnormal heart rate variability and new onset of chronic kidney disease in patients with type 2 diabetes: a ten-year follow-up study. Diabetes Res Clin Pract 108(1):31–37. doi:10.1016/j.diabres.2015.01.031

    Article  PubMed  Google Scholar 

  36. Goff DC Jr, Lloyd-Jones DM, Bennett G, Coady S, D’Agostino RB, Gibbons R, Greenland P, Lackland DT, Levy D (2014) 2013 ACC/AHA guideline on the assessment of cardiovascular risk: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. Circulation 129(25 Suppl 2):S49–S73. doi:10.1161/01.cir.0000437741.48606.98

    Article  PubMed  Google Scholar 

  37. Chiang SS, Lee CL, Liu HC, Wang JS, Lee IT, Song YM, Fu CP, Li YF, Sheu WH, Lin SY (2016) Physical activity and albuminuria were associated with painful diabetic polyneuropathy in type 2 diabetes in an ethnic Chinese population. Clin Chim Acta 462:55–59. doi:10.1016/j.cca.2016.08.022

    Article  CAS  PubMed  Google Scholar 

  38. Gong H, Pa L, Wang K, Mu H, Dong F, Ya S, Xu G, Tao N, Pan L, Wang B, Shan G (2015) Prevalence of diabetes and associated factors in the Uyghur and Han population in Xinjiang, China. Int J Environ Res Public Health 12(10):12792–12802. doi:10.3390/ijerph121012792

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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  1. Department of Endocrinology, The First Affiliated Hospital of Fujian Medical University, 20 Cha Zhong Road, Fuzhou, Fujian, 350005, China

    Yongze Zhang, Ying Jiang, Ximei Shen & Sunjie Yan

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Sunjie Yan conducted the design of the study and reviewed/edited the drafts, and is guarantor. Yongze Zhang researched data and edited the drafts and contributed to discussion. Ying Jiang wrote manuscript. Ximei Shen cowrote the final draft.

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Correspondence to Sunjie Yan.

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Zhang, Y., Jiang, Y., Shen, X. et al. Can both normal and mildly abnormal albuminuria and glomerular filtration rate be a danger signal for diabetic peripheral neuropathy in type 2 diabetes mellitus?. Neurol Sci 38, 1381–1390 (2017). https://doi.org/10.1007/s10072-017-2946-1

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