Journal of Endocrinological Investigation

, Volume 38, Issue 5, pp 513–518 | Cite as

Serum 25-hydroxyvitamin D levels and peripheral neuropathy in patients with type 2 diabetes: a systematic review and meta-analysis

  • W. S. Lv
  • W. J. Zhao
  • S. L. Gong
  • D. D. Fang
  • B. Wang
  • Z. J. Fu
  • S. L. Yan
  • Y. G. Wang
Original Article



Vitamin D is a multifunctional pro-hormone and has widespread actions in human body. Several studies showed a possible association between vitamin D deficiency and diabetic peripheral neuropathy (DPN) in patients with type 2 diabetes, but no definite conclusion was available.


A systematic review and meta-analysis was performed to comprehensively assess the association between serum 25-hydroxyvitamin D [25(OH)D] levels and DPN in patients with type 2 diabetes. Data from eligible studies were pooled using meta-analysis.


Six studies that involved a total of 1,484 type 2 diabetic patients were finally included into the meta-analysis. Meta-analysis showed that there were obviously decreased serum 25(OH)D levels in DPN patients [weighted mean difference (WMD) = −6.36 ng/ml, 95 % confidence interval (95 % CI) −8.57 to −4.14, P < 0.00001]. Vitamin D deficiency was also significantly associated with increased risk of DPN in patients with type 2 diabetes [odds ratio (OR) 2.88, 95 % CI 1.84–4.50, P < 0.00001]. Meta-analysis of three studies with adjusted estimates showed that vitamin D deficiency was independently associated with increased risk of DPN in patients with type 2 diabetes (OR 2.68, 95 % CI 1.67–4.30, P < 0.0001). Sensitivity analysis showed that there was no obvious change in the pooled estimates.


Vitamin D is involved in the development of DPN in type 2 diabetic patients, and vitamin D deficiency is very likely to be associated with DPN in type 2 diabetic patients. Further studies are needed to validate the association between vitamin D deficiency and DPN.


Diabetic peripheral neuropathy 25-Hydroxyvitamin D Meta-analysis 


Conflict of interest

We declare that we have no conflicts of interest.


  1. 1.
    Callaghan BC, Cheng HT, Stables CL, Smith AL, Feldman EL (2012) Diabetic neuropathy: clinical manifestations and current treatments. Lancet Neurol 11(6):521–534CrossRefPubMedCentralPubMedGoogle Scholar
  2. 2.
    Tesfaye S, Selvarajah D (2012) Advances in the epidemiology, pathogenesis and management of diabetic peripheral neuropathy. Diabetes Metab Res Rev 28(S1):8–14CrossRefPubMedGoogle Scholar
  3. 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):261–270CrossRefPubMedGoogle Scholar
  4. 4.
    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):465–471CrossRefPubMedGoogle Scholar
  5. 5.
    Van Belle TL, Gysemans C, Mathieu C (2013) Vitamin D and diabetes: the odd couple. Trends Endocrinol Metab 24(11):561–568CrossRefPubMedGoogle Scholar
  6. 6.
    Abrams SA, Coss-Bu JA, Tiosano D (2013) Vitamin D: effects on childhood health and disease. Nat Rev Endocrinol 9(3):162–170CrossRefPubMedGoogle Scholar
  7. 7.
    Hollis BW, Wagner CL (2013) Clinical review: the role of the parent compound vitamin D with respect to metabolism and function: why clinical dose intervals can affect clinical outcomes. J Clin Endocrinol Metab 98(12):4619–4628CrossRefPubMedCentralPubMedGoogle Scholar
  8. 8.
    Kunutsor SK, Burgess S, Munroe PB, Khan H (2014) Vitamin D and high blood pressure: causal association or epiphenomenon? Eur J Epidemiol 29(1):1–14CrossRefPubMedGoogle Scholar
  9. 9.
    Yang CY, Leung PS, Adamopoulos IE, Gershwin ME (2013) The implication of vitamin D and autoimmunity: a comprehensive review. Clin Rev Allergy Immunol 45(2):217–226CrossRefPubMedGoogle Scholar
  10. 10.
    Hurskainen AR, Virtanen JK, Tuomainen TP, Nurmi T, Voutilainen S (2012) Association of serum 25-hydroxyvitamin D with type 2 diabetes and markers of insulin resistance in a general older population in Finland. Diabetes Metab Res Rev 28(5):418–423CrossRefPubMedGoogle Scholar
  11. 11.
    Pinelli NR, Jaber LA, Brown MB, Herman WH (2010) Serum 25-hydroxy vitamin d and insulin resistance, metabolic syndrome, and glucose intolerance among Arab Americans. Diabetes Care 33(6):1373–1375CrossRefPubMedCentralPubMedGoogle Scholar
  12. 12.
    Skalli S, Muller M, Pradines S, Halimi S, Wion-Barbot N (2012) Vitamin D deficiency and peripheral diabetic neuropathy. Eur J Intern Med 23(2):e67–e68CrossRefPubMedGoogle Scholar
  13. 13.
    Soderstrom LH, Johnson SP, Diaz VA, Mainous AG 3rd (2012) Association between vitamin D and diabetic neuropathy in a nationally representative sample: results from 2001 to 2004 NHANES. Diabet Med 29(1):50–55CrossRefPubMedCentralPubMedGoogle Scholar
  14. 14.
    Shehab D, Al-Jarallah K, Mojiminiyi OA, Al Mohamedy H, Abdella NA (2012) Does vitamin D deficiency play a role in peripheral neuropathy in type 2 diabetes? Diabet Med 29(1):43–49CrossRefPubMedGoogle Scholar
  15. 15.
    Celikbilek A, Gocmen AY, Tanik N, et al. (2014) Decreased serum vitamin D levels are associated with diabetic peripheral neuropathy in a rural area of Turkey. Acta Neurol Belg [Epub ahead of print]Google Scholar
  16. 16.
    Wells G, Shea B, O’connell D, et al. (2012) The Newcastle–Ottawa scale (NOS) for assessing the quality of nonrandomised studies in meta-analyses. Ottawa Health Research Institute WebsiteGoogle Scholar
  17. 17.
    Cochran WG (1954) The combination of estimates from different experiments. Biometrics 10(1):101–129CrossRefGoogle Scholar
  18. 18.
    Higgins JP, Thompson SG, Deeks JJ, Altman DG (2003) Measuring inconsistency in meta-analyses. BMJ 327(7414):557–560CrossRefPubMedCentralPubMedGoogle Scholar
  19. 19.
    DerSimonian R, Laird N (1986) Meta-analysis in clinical trials. Control Clin Trials 7(3):177–188CrossRefPubMedGoogle Scholar
  20. 20.
    Mantel N, Haenszel W (1959) Statistical aspects of the analysis of data from retrospective studies of disease. J Natl Cancer Inst 22(4):719–748PubMedGoogle Scholar
  21. 21.
    Egger M, Davey Smith G, Schneider M, Minder C (1997) Bias in meta-analysis detected by a simple, graphical test. BMJ 315(7109):629–634CrossRefPubMedCentralPubMedGoogle Scholar
  22. 22.
    Peters JL, Sutton AJ, Jones DR, Abrams KR, Rushton L (2007) Performance of the trim and fill method in the presence of publication bias and between-study heterogeneity. Stat Med 26(25):4544–4562CrossRefPubMedGoogle Scholar
  23. 23.
    Putz Z, Martos T, Nemeth N et al (2013) Vitamin D and neuropathy. Orv Hetil 154(51):2012–2015CrossRefPubMedGoogle Scholar
  24. 24.
    Ahmadieh H, Azar ST, Lakkis N, Arabi A (2013) Hypovitaminosis d in patients with type 2 diabetes mellitus: a relation to disease control and complications. ISRN Endocrinol 2013:641098Google Scholar
  25. 25.
    Zubair M, Malik A, Meerza D, Ahmad J (2013) 25-Hydroxyvitamin D [25(OH)D] levels and diabetic foot ulcer: is there any relationship? Diabetes Metab Syndr 7(3):148–153CrossRefPubMedGoogle Scholar
  26. 26.
    Zhang JP, Xu N, Yi D et al (2014) Association between the level of serum vitamin D and peripheral neuropathy in type 2 diabetic patients [article in Chinese]. Chin J Endocrinol Metab 30(5):385–387Google Scholar
  27. 27.
    Maser RE, Lenhard MJ, Pohlig RT (2014) Vitamin D insufficiency is associated with reduced parasympathetic nerve fiber function in type 2 diabetes. Endocr Pract 1–22 [Epub ahead of print]Google Scholar
  28. 28.
    Feldman D, Krishnan AV, Swami S, Giovannucci E, Feldman BJ (2014) The role of vitamin D in reducing cancer risk and progression. Nat Rev Cancer 14(5):342–357CrossRefPubMedGoogle Scholar
  29. 29.
    Pludowski P, Holick MF, Pilz S et al (2013) Vitamin D effects on musculoskeletal health, immunity, autoimmunity, cardiovascular disease, cancer, fertility, pregnancy, dementia and mortality—a review of recent evidence. Autoimmun Rev 12(10):976–989CrossRefPubMedGoogle Scholar
  30. 30.
    Donath MY, Shoelson SE (2011) Type 2 diabetes as an inflammatory disease. Nat Rev Immunol 11(2):98–107CrossRefPubMedGoogle Scholar
  31. 31.
    Verrotti A, Loiacono G, Mohn A, Chiarelli F (2009) New insights in diabetic autonomic neuropathy in children and adolescents. Eur J Endocrinol 161(6):811–818CrossRefPubMedGoogle Scholar

Copyright information

© Italian Society of Endocrinology (SIE) 2014

Authors and Affiliations

  • W. S. Lv
    • 1
  • W. J. Zhao
    • 1
  • S. L. Gong
    • 1
  • D. D. Fang
    • 1
  • B. Wang
    • 1
    • 2
  • Z. J. Fu
    • 1
  • S. L. Yan
    • 1
  • Y. G. Wang
    • 1
  1. 1.Department of EndocrinologyAffiliated Hospital of Qingdao UniversityQingdaoChina
  2. 2.Essencemed ClinicWeifangChina

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