Skip to main content
Top
Published in: Current Diabetes Reports 10/2014

01-10-2014 | Microvascular Complications—Neuropathy (D Ziegler, Section Editor)

Is There an Association Between Diabetic Neuropathy and Low Vitamin D Levels?

Authors: Zsuzsanna Putz, Tímea Martos, Nóra Németh, Anna Erzsébet Körei, Orsolya Erzsébet Vági, Miklós Soma Kempler, Péter Kempler

Published in: Current Diabetes Reports | Issue 10/2014

Login to get access

Abstract

In the past few years, the effects of vitamin D that go beyond its relationship with bone metabolism have come into the focus of scientific attention. Research concerning diabetes and its complications has become a public health priority. An increasing number of reports link vitamin D deficiency to diabetes; however, so far, there has only been limited and contradictory data available on the correlation between diabetic peripheral neuropathy and vitamin D. Studies of people with type 2 diabetes confirmed the relationship between vitamin D deficiency and neuropathy incidence as well as the severity of the symptoms caused by neuropathy. The latest studies are also suggesting a relationship between the incidence of plantar ulcers and vitamin D deficiency.
Literature
1.
go back to reference Chowdhury R, Kunutsor S, Vitezova A, Oliver-Williams C, Chowdhury S, Kiefte-de-Jong JC, et al. Vitamin D and risk of cause specific death: systematic review and meta-analysis of observational cohort and randomised intervention studies. BMJ. 2014;348:g1903.PubMedCrossRefPubMedCentral Chowdhury R, Kunutsor S, Vitezova A, Oliver-Williams C, Chowdhury S, Kiefte-de-Jong JC, et al. Vitamin D and risk of cause specific death: systematic review and meta-analysis of observational cohort and randomised intervention studies. BMJ. 2014;348:g1903.PubMedCrossRefPubMedCentral
2.
go back to reference International Diabetes Federation. IDF Diabetes Atlas 6th edn. Brussels: International Diabetes Federation; 2013. International Diabetes Federation. IDF Diabetes Atlas 6th edn. Brussels: International Diabetes Federation; 2013.
3.
go back to reference Wolden-Kirk H, Rondas D, Bugliani M, Korf H, Van Lommel L, Brusgaard K, et al. Discovery of molecular pathways mediating 1,25-dihydroxyvitamin D3 protection against cytokine-induced inflammation and damage of human and male mouse islets of Langerhans. Endocrinology. 2014;155(3):736–47.PubMedCrossRef Wolden-Kirk H, Rondas D, Bugliani M, Korf H, Van Lommel L, Brusgaard K, et al. Discovery of molecular pathways mediating 1,25-dihydroxyvitamin D3 protection against cytokine-induced inflammation and damage of human and male mouse islets of Langerhans. Endocrinology. 2014;155(3):736–47.PubMedCrossRef
4.
go back to reference Raab J, Giannopoulou EZ, Schneider S, Warncke K, Krasmann M, Winkler C, et al. Prevalence of vitamin D deficiency in pre-type 1 diabetes and its association with disease progression. Diabetologia. 2014;57(5):902–8.PubMedCrossRef Raab J, Giannopoulou EZ, Schneider S, Warncke K, Krasmann M, Winkler C, et al. Prevalence of vitamin D deficiency in pre-type 1 diabetes and its association with disease progression. Diabetologia. 2014;57(5):902–8.PubMedCrossRef
5.
go back to reference Scragg R, Sowers M, Bell C. Third National Health and Nutrition Examination Survey, serum 25-hydroxyvitamin D, diabetes, and ethnicity in the Third National Health and Nutrition Examination Survey. Diabetes Care. 2004;27(12):2813–8.PubMedCrossRef Scragg R, Sowers M, Bell C. Third National Health and Nutrition Examination Survey, serum 25-hydroxyvitamin D, diabetes, and ethnicity in the Third National Health and Nutrition Examination Survey. Diabetes Care. 2004;27(12):2813–8.PubMedCrossRef
6.
go back to reference Putz Z, Hermányi Z, Tóth N, Istenes I, Keresztes K, Jermendy G, et al. A distalis típusú, sensoros neuropathia diagnosztikája a diabetológiai gyakorlatban. Diabetologia Hungarica. 2008;16:157–64. Putz Z, Hermányi Z, Tóth N, Istenes I, Keresztes K, Jermendy G, et al. A distalis típusú, sensoros neuropathia diagnosztikája a diabetológiai gyakorlatban. Diabetologia Hungarica. 2008;16:157–64.
7.
go back to reference Zs P, Kempler P, Jermendy G. Diabetes specifikus szövődmények prediabetesben. Orv Hetil. 2009;150(47):2139–45.CrossRef Zs P, Kempler P, Jermendy G. Diabetes specifikus szövődmények prediabetesben. Orv Hetil. 2009;150(47):2139–45.CrossRef
8.
go back to reference Ziegler D. Diabetic cardiovascular autonomic neuropathy: prognosis, diagnosis and treatment. Diabetes Metab Rev. 1994;10(4):339–83.PubMedCrossRef Ziegler D. Diabetic cardiovascular autonomic neuropathy: prognosis, diagnosis and treatment. Diabetes Metab Rev. 1994;10(4):339–83.PubMedCrossRef
9.
go back to reference Eyles DW, Smith S, Kinobe R, Hewison M, McGrath JJ. Distribution of the vitamin D receptor and 1 alpha-hydroxylase in human brain. J Chem Neuroanat. 2005;29:21–30.PubMedCrossRef Eyles DW, Smith S, Kinobe R, Hewison M, McGrath JJ. Distribution of the vitamin D receptor and 1 alpha-hydroxylase in human brain. J Chem Neuroanat. 2005;29:21–30.PubMedCrossRef
10.
go back to reference Freedman DM, Dosemeci M, Alavanja MC. Mortality from multiple sclerosis and exposure to residential and occupational solar radiation: a case–control study based on death certificates. Occup Environ Me. 2000;57:418–21.CrossRef Freedman DM, Dosemeci M, Alavanja MC. Mortality from multiple sclerosis and exposure to residential and occupational solar radiation: a case–control study based on death certificates. Occup Environ Me. 2000;57:418–21.CrossRef
11.
go back to reference Munger KL, Levin LI, Hollis BW, Howard NS, Ascherio A. Serum 25-hydroxyvitamin D levels and risk of multiple sclerosis. JAMA. 2006;296:2832–8.PubMedCrossRef Munger KL, Levin LI, Hollis BW, Howard NS, Ascherio A. Serum 25-hydroxyvitamin D levels and risk of multiple sclerosis. JAMA. 2006;296:2832–8.PubMedCrossRef
12.
go back to reference van der Mei IA, Ponsonby AL, Dwyer T, Blizzard L, Taylor BV, Kilpatrick T, et al. Vitamin D levels in people with multiple sclerosis and community controls in Tasmania, Australia. J Neurol. 2007;254:581–90.PubMedCrossRef van der Mei IA, Ponsonby AL, Dwyer T, Blizzard L, Taylor BV, Kilpatrick T, et al. Vitamin D levels in people with multiple sclerosis and community controls in Tasmania, Australia. J Neurol. 2007;254:581–90.PubMedCrossRef
13.
go back to reference Simpson Jr S, Taylor B, Blizzard L, Ponsonby AL, Pittas F, Tremlett H, et al. I., Higher 25-hydroxyvitamin D is associated with lower relapse risk in multiple sclerosis. Ann Neurol. 2010;68:193–203.PubMed Simpson Jr S, Taylor B, Blizzard L, Ponsonby AL, Pittas F, Tremlett H, et al. I., Higher 25-hydroxyvitamin D is associated with lower relapse risk in multiple sclerosis. Ann Neurol. 2010;68:193–203.PubMed
14.
go back to reference Soilu-Hänninen M, Laaksonen M, Laitinen I, Erälinna JP, Lilius EM, Mononen I. A longitudinal study of serum 25-hydroxyvitamin D and intact parathyroid hormone levels indicate the importance of vitamin D and calcium homeostasis regulation in multiple sclerosis. J Neurol Neurosurg Psychiatry. 2008;79:152–7.PubMedCrossRef Soilu-Hänninen M, Laaksonen M, Laitinen I, Erälinna JP, Lilius EM, Mononen I. A longitudinal study of serum 25-hydroxyvitamin D and intact parathyroid hormone levels indicate the importance of vitamin D and calcium homeostasis regulation in multiple sclerosis. J Neurol Neurosurg Psychiatry. 2008;79:152–7.PubMedCrossRef
15.
go back to reference Mowry EM, Krupp LB, Milazzo M, Chabas D, Strober JB, Belman AL, et al. Vitamin D status is associated with relapse rate in pediatric-onset multiple sclerosis. Ann Neurol. 2010;67:618–24.PubMed Mowry EM, Krupp LB, Milazzo M, Chabas D, Strober JB, Belman AL, et al. Vitamin D status is associated with relapse rate in pediatric-onset multiple sclerosis. Ann Neurol. 2010;67:618–24.PubMed
16.
go back to reference Correale J, Ysrraelit MC, Gaitán MI. Immunmodulatory effects of vitamin D in multiple sclerosis. Brain. 2009;132:1146–60.PubMedCrossRef Correale J, Ysrraelit MC, Gaitán MI. Immunmodulatory effects of vitamin D in multiple sclerosis. Brain. 2009;132:1146–60.PubMedCrossRef
17.
go back to reference Burton JM, Kimball S, Vieth R, Bar-Or A, Dosch HM, Cheung R, et al. A phase I/II doseescalation trial of vitamin D3 and calcium in multiple sclerosis. Neurology. 2010;74:1852–9.PubMedCrossRefPubMedCentral Burton JM, Kimball S, Vieth R, Bar-Or A, Dosch HM, Cheung R, et al. A phase I/II doseescalation trial of vitamin D3 and calcium in multiple sclerosis. Neurology. 2010;74:1852–9.PubMedCrossRefPubMedCentral
18.
go back to reference Smolders J, Hupperts R, Barkhof F, Grimaldi LM, Holmoy T, Killestein J, et al. Efficacy of vitamin D(3) as add-on therapy in patients with relapsing-remitting multiple sclerosis receiving subcutaneous interferon beta-1a: a Phase II, multicenter, double-blind, randomized, placebo-controlled trial. J Neurol Sci. 2011;311:44–9.PubMedCrossRef Smolders J, Hupperts R, Barkhof F, Grimaldi LM, Holmoy T, Killestein J, et al. Efficacy of vitamin D(3) as add-on therapy in patients with relapsing-remitting multiple sclerosis receiving subcutaneous interferon beta-1a: a Phase II, multicenter, double-blind, randomized, placebo-controlled trial. J Neurol Sci. 2011;311:44–9.PubMedCrossRef
19.
go back to reference Llewellyn DJ, Lang IA, Langa KM, Muniz-Terrera G, Phillips CL, Cherubini A, et al. Vitamin D and risk of cognitive decline in elderly persons. Arch Intern Med. 2010;170(13):1135–41.PubMedCrossRefPubMedCentral Llewellyn DJ, Lang IA, Langa KM, Muniz-Terrera G, Phillips CL, Cherubini A, et al. Vitamin D and risk of cognitive decline in elderly persons. Arch Intern Med. 2010;170(13):1135–41.PubMedCrossRefPubMedCentral
20.
go back to reference Knekt P, Kilkkinen A, Rissanen H, Marniemi J, Sääksjärvi K, Heliövaara M. Serum vitamin D and the risk of Parkinson disease. Arch Neurol. 2010;67(7):808–11.PubMedCrossRefPubMedCentral Knekt P, Kilkkinen A, Rissanen H, Marniemi J, Sääksjärvi K, Heliövaara M. Serum vitamin D and the risk of Parkinson disease. Arch Neurol. 2010;67(7):808–11.PubMedCrossRefPubMedCentral
21.
go back to reference Ding H, Dhima K, Lockhart KC, Locascio JJ, Hoesing AN, Duong K, et al. Unrecognized vitamin D3 deficiency is common in Parkinson disease: Harvard Biomarker Study. Neurology. 2013;81(17):1531–7.PubMedCrossRef Ding H, Dhima K, Lockhart KC, Locascio JJ, Hoesing AN, Duong K, et al. Unrecognized vitamin D3 deficiency is common in Parkinson disease: Harvard Biomarker Study. Neurology. 2013;81(17):1531–7.PubMedCrossRef
22.
go back to reference Lee P, Chen R. Vitamin D as an analgesic for patients with type 2 diabetes and neuropathic pain. Arch Intern Med. 2008;168:771–2.PubMedCrossRef Lee P, Chen R. Vitamin D as an analgesic for patients with type 2 diabetes and neuropathic pain. Arch Intern Med. 2008;168:771–2.PubMedCrossRef
23.
go back to reference Shebab D, Al-Jarallah K, Mojiminiyi OA, Al Mohamedy H, Abdella NA. Does vitamin D deficiency play a role in peripheral neuropathy in type 2 diabetes? Diabet Med. 2012;29:43–9.CrossRef Shebab D, Al-Jarallah K, Mojiminiyi OA, Al Mohamedy H, Abdella NA. Does vitamin D deficiency play a role in peripheral neuropathy in type 2 diabetes? Diabet Med. 2012;29:43–9.CrossRef
24.
go back to reference Valensi P, Devehat C, Richard JL, Farez C, Khodabandehlou T, Rosenbloom RA, et al. A multicenter double blind, safety study of QR-333 for treatment of symptomatic diabetic peripheral neuropathy: a preliminary report. J Diabetes Complicat. 2005;19:247–53.PubMedCrossRef Valensi P, Devehat C, Richard JL, Farez C, Khodabandehlou T, Rosenbloom RA, et al. A multicenter double blind, safety study of QR-333 for treatment of symptomatic diabetic peripheral neuropathy: a preliminary report. J Diabetes Complicat. 2005;19:247–53.PubMedCrossRef
25.••
go back to reference Soderstrom LH, Johnson SP, Diaz VA, Mainous 3rd AG. Association between vitamin D and diabetic neuropathy in a nationally reperesentative sample: results from 2001–2004 NHANES. Diabet Med. 2012;29:50–5. This study analyses a representative sample, proving that Vitamin D is insufficiency associated with self-reported peripheral neuropathy symptoms. PubMedCrossRefPubMedCentral Soderstrom LH, Johnson SP, Diaz VA, Mainous 3rd AG. Association between vitamin D and diabetic neuropathy in a nationally reperesentative sample: results from 2001–2004 NHANES. Diabet Med. 2012;29:50–5. This study analyses a representative sample, proving that Vitamin D is insufficiency associated with self-reported peripheral neuropathy symptoms. PubMedCrossRefPubMedCentral
26.
go back to reference Skalli S, Muller M, Pradines S, Halimi S, Wion-Barbot N. Vitamin D deficiency and peripheral diabetic neuropathy. Eur J Intern Med. 2012;23:67–8.CrossRef Skalli S, Muller M, Pradines S, Halimi S, Wion-Barbot N. Vitamin D deficiency and peripheral diabetic neuropathy. Eur J Intern Med. 2012;23:67–8.CrossRef
27.
go back to reference Ahmadieh H, Azar ST, Lakkis N, Arabi A. Hypovitaminosis D in patients with type 2 diabetes mellitus: a relation to disease control and complications. ISRN Endocrinol. 2013;22(2013):641098. Ahmadieh H, Azar ST, Lakkis N, Arabi A. Hypovitaminosis D in patients with type 2 diabetes mellitus: a relation to disease control and complications. ISRN Endocrinol. 2013;22(2013):641098.
28.
go back to reference Riaz S, Malcangio M, Miller M, Tomlinson DR. A vitamin D3 derivative (CB1093) induces nerve growth factor and prevents neurothrophic deficits in streptozotocin-diabetic rats. Diabetologia. 1999;42:1308–13.PubMedCrossRef Riaz S, Malcangio M, Miller M, Tomlinson DR. A vitamin D3 derivative (CB1093) induces nerve growth factor and prevents neurothrophic deficits in streptozotocin-diabetic rats. Diabetologia. 1999;42:1308–13.PubMedCrossRef
29.
go back to reference Riaz S, Tomlinson DR. Pharmacological modulation of nerve growth factor synthesis: a mechanistic comparison of vitamin D receptor and beta(2)-adrenoreceptor agonists. Brain Res Mol. 2000;85:179–88.CrossRef Riaz S, Tomlinson DR. Pharmacological modulation of nerve growth factor synthesis: a mechanistic comparison of vitamin D receptor and beta(2)-adrenoreceptor agonists. Brain Res Mol. 2000;85:179–88.CrossRef
30.
go back to reference Filipović N, Ferhatović L, Marelja I, Puljak L, Grković I. Increased vitamin D receptor expression in dorsal root ganglia neurons of diabetic rats. Neurosci Lett. 2013;9(549):140–5.CrossRef Filipović N, Ferhatović L, Marelja I, Puljak L, Grković I. Increased vitamin D receptor expression in dorsal root ganglia neurons of diabetic rats. Neurosci Lett. 2013;9(549):140–5.CrossRef
31.
go back to reference Plotnikoff GA, Quigley JM. Prevalence of severe hypovitaminosis D in patients with persistent, nonspecific musculosceletal pain. Mayo Clin Proc. 2003;78:1463–70.PubMedCrossRef Plotnikoff GA, Quigley JM. Prevalence of severe hypovitaminosis D in patients with persistent, nonspecific musculosceletal pain. Mayo Clin Proc. 2003;78:1463–70.PubMedCrossRef
32.
go back to reference Bell DSH, Reversal of the symptoms of diabetic neuropathy through correction of vitamin D deficiency in a type 1 diabetic patient. Case Report in Endocrinology, 2012: p. 1–3. Bell DSH, Reversal of the symptoms of diabetic neuropathy through correction of vitamin D deficiency in a type 1 diabetic patient. Case Report in Endocrinology, 2012: p. 1–3.
33.
go back to reference Bell DSH. Protean manifestations of vitamin D deficiency, part 2: deficiency and its association with autotoimmune disease, cancer, infection, asthma, dermopathies, insulin resistance, and type 2 diabetes. South Med J. 2011;335–339:335–9.CrossRef Bell DSH. Protean manifestations of vitamin D deficiency, part 2: deficiency and its association with autotoimmune disease, cancer, infection, asthma, dermopathies, insulin resistance, and type 2 diabetes. South Med J. 2011;335–339:335–9.CrossRef
34.
go back to reference Van Etten E, Branisteanu DD, Verstuyf A, Waer M, Bouillon R, Mathieu C. Analogs of 1,25-dihydroxyvitamin D3 as dose-reducing agents for classical immunosuppressants. Transplantation. 2000;69:1932–42.PubMedCrossRef Van Etten E, Branisteanu DD, Verstuyf A, Waer M, Bouillon R, Mathieu C. Analogs of 1,25-dihydroxyvitamin D3 as dose-reducing agents for classical immunosuppressants. Transplantation. 2000;69:1932–42.PubMedCrossRef
35.•
go back to reference Zubair M, Malik A, Meerza D, Ahmad J. 25-hydroxyvitamin D [25(OH)D] levels and diabetic foot ulcer: is there any relationship? Diabetes Metab Synd. 2013;7:148–53. Diabetic foot ulcer is a burden for the developed industrial countries, nearly half of all lower-leg amputations of a non-traumatic origin are performed on patients with diabetes. Vitamin D have a possible effect in decreasing this huge number. CrossRef Zubair M, Malik A, Meerza D, Ahmad J. 25-hydroxyvitamin D [25(OH)D] levels and diabetic foot ulcer: is there any relationship? Diabetes Metab Synd. 2013;7:148–53. Diabetic foot ulcer is a burden for the developed industrial countries, nearly half of all lower-leg amputations of a non-traumatic origin are performed on patients with diabetes. Vitamin D have a possible effect in decreasing this huge number. CrossRef
36.
go back to reference Hutchinson MS, Figenschau Y, Njølstad I, Schirmer H, Jorde R. Serum 25-hydroxyvitamin D levels are inversely associated with glycated haemoglobin (HbA(1c)). The Tromsø Study. Scand J Clin Lab Invest. 2011;71(5):399–406.PubMedCrossRef Hutchinson MS, Figenschau Y, Njølstad I, Schirmer H, Jorde R. Serum 25-hydroxyvitamin D levels are inversely associated with glycated haemoglobin (HbA(1c)). The Tromsø Study. Scand J Clin Lab Invest. 2011;71(5):399–406.PubMedCrossRef
37.
go back to reference Zoppini G, Galletti A, Targher G, Brangani C, Pichiri I, Negri C, et al. Glycated haemoglobin is inversely related to serum vitamin D levels in type 2 diabetic patients. PLoS One. 2013;8(12):e82733.PubMedCrossRefPubMedCentral Zoppini G, Galletti A, Targher G, Brangani C, Pichiri I, Negri C, et al. Glycated haemoglobin is inversely related to serum vitamin D levels in type 2 diabetic patients. PLoS One. 2013;8(12):e82733.PubMedCrossRefPubMedCentral
Metadata
Title
Is There an Association Between Diabetic Neuropathy and Low Vitamin D Levels?
Authors
Zsuzsanna Putz
Tímea Martos
Nóra Németh
Anna Erzsébet Körei
Orsolya Erzsébet Vági
Miklós Soma Kempler
Péter Kempler
Publication date
01-10-2014
Publisher
Springer US
Published in
Current Diabetes Reports / Issue 10/2014
Print ISSN: 1534-4827
Electronic ISSN: 1539-0829
DOI
https://doi.org/10.1007/s11892-014-0537-6

Other articles of this Issue 10/2014

Current Diabetes Reports 10/2014 Go to the issue

Diabetes and Other Diseases-Emerging Associations (JJ Nolan, Section Editor)

The Epidemiology of Diabetes and Cancer

Microvascular Complications—Neuropathy (D Ziegler, Section Editor)

The Role of Sodium Channels in Painful Diabetic and Idiopathic Neuropathy

Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin
Prof. Florian Limbourg
Prof. Anoop Chauhan
Developed by: Springer Medicine
Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.

Year in Review: Pulmonary vascular disease

The last year's highlights in pulmonary vascular disease are presented by Dr. Jane Leopold in this official video from ACC.24.

Year in Review: Valvular heart disease

Watch Prof. William Zoghbi present the last year's highlights in valvular heart disease from the official ACC.24 Year in Review session.

Year in Review: Heart failure and cardiomyopathies

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.