Research Update Journal of Medicine
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Volume 1Issue 1
Medicine|Mini-Review
| October 19, 2020
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Association between vitamin D deficiency and diabetic neuropathy- a review

Maitree Patel, Faisal Sheriff

Cite as: Patel M, Sheriff F. Association between vitamin D deficiency and diabetic neuropathy- a review. Research Update Journal of Medicine. 2020;1(1):003.

Highlights

Prior knowledge about this subject

  • Some studies have shown that low serum vitamin D levels are an independent predictor of diabetic polyneuropathy, the evidence on the role of vitamin D replacements in improving symptoms of neuropathy are limited.

Findings of this study

  • Patients suffering from vitamin D deficiency for any reason, develop insulin resistance which in turn leads to worsening symptoms related to nerve damage.
  • Vitamin D-associated improvements in axon regeneration and myelination following nerve injury, as well as increases in nerve growth factor synthesis and prevention of neuronal degeneration. 
  • Furthermore, another potential positive effect of Vitamin D is that it may favorably alter coronary calcification, which is a precursor of vascular events and a common finding in Type 2 diabetes.

Impact of this study in clinical practice

  • Vitamin D supplementation to not only prevent the progression of diabetic neuropathy but also reduce the severe pain associated with damage to the microvasculature.

Abstract

Diabetes is a highly prevalent disease in first world countries. Most of these patients go on to develop diabetic polyneuropathy. Though there are several factors that contribute to neuropathy, of interest is how vitamin D contributes to this disease. More specifically, vitamin D deficiency not only contributes to diabetic neuropathy but also seems to worsen neuropathic pain symptoms in such patients. Some of the mechanisms involve calcium transport while others involve the enzymatic activities in the pancreas. Treatment may involve supplementation of vitamin D, but there are other factors involved in diabetic neuropathy other than vitamin D deficiency which needs to be taken into consideration.

Keywords: vitamin D deficiency; diabetic neuropathy; microvasculature; hypovitaminosis; vitamin D replacements

Introduction

Diabetic neuropathy entails nerve damage which is caused by the destructive effects of high blood sugar on the nerves. Patients can attain symptoms based on the area of nerve damage which can involve sensory nerves, motor nerves, and autonomic nervous systems. It has been thought that these changes can be brought about by injury to the microvasculature that supplies the nerves [1].  Different risk factors of this include disease duration of diabetes, age, glycosylated hemoglobin A1c (HbA1c), diabetic retinopathy (DR), smoking, kidney damage, and body mass index (BMI) [2]. There is little evidence that suggests that vitamin D deficiency could be associated with the development of both type 1 and type 2 diabetes which in turn can lead to painful neuropathy. Since some studies have shown that low serum vitamin D levels are an independent predictor of diabetic polyneuropathy, the question arises whether or not vitamin D replacements (VDRs) can improve symptoms of neuropathy.

Materials & Methods

Results

Discussion

The developed countries have a high incidence of diabetic polyneuropathy which is reported in 10–50% of patients with diabetes. At the time of diagnosis, neuropathy is present in 10% of diabetic patients and overall in 50% of patients with a 25-year history of the disease [3]. Hypovitaminosis D is highly prevalent in patients with Type 2 diabetes and could be a precursor to the development of diabetic neuropathy by causing neurotrophic deficits. First, the β-cell in the pancreas that secretes insulin has been shown to contain VDRs as well as the 1 alpha-hydroxylase enzyme. Vitamin D deficiency leads to reduced insulin secretion and is known to increase the levels of parathyroid hormone. Additionally, Vitamin D contributes to the normalization of extracellular calcium, ensuring normal calcium flux through cell membranes; therefore, low vitamin D may diminish calcium’s ability to affect insulin secretion. This in turn has been linked to increased insulin resistance, which is associated with diabetes, hypertension, inflammation, and increased cardiovascular risk [4].  

Evidence indicates that vitamin D treatment improves glucose tolerance and insulin resistance. Supplementation with vitamin D has been shown to restore insulin secretion in animals. Researchers have found an indirect effect on insulin secretion, potentially by a calcium effect on insulin secretion. Other potential mechanisms associated with vitamin D and diabetes include improving insulin action by stimulating expression of the insulin receptor, enhancing insulin responsiveness for glucose transport, having an indirect effect on insulin action potentially via a calcium effect on insulin secretion, and improving systemic inflammation by a direct effect on cytokines [5]. One study on research that showed vitamin D-associated improvements in axon regeneration and myelination following nerve injury, as well as increases in nerve growth factor synthesis and prevention of neuronal degeneration [6] Furthermore, another potential positive effect of Vitamin D is that it may favorably alter coronary calcification, which is a precursor of vascular events and a common finding in Type 2 diabetes [7]. Derangements in vitamin D levels have been shown to contribute to insulin resistance through several mechanisms. This in turn has led to painful diabetic neuropathy. Vitamin D insufficiency is associated with self‐reported peripheral neuropathy symptoms even after adjusting for demographic factors, obesity, co‐morbidities, use of medications for neuropathy and diabetes duration, and control [8].  Vitamin D supplementation could further add value to the treatment of painful peripheral diabetic neuropathy [9]. A single high-dose of intramuscular vitamin D appears to be a safe and effective treatment for PDN [10].

Conclusion

Diabetic neuropathy is a debilitating condition that disrupts everyday life for patients. Among the many aspects that contribute to diabetic neuropathy, vitamin D deficiency is an independent factor that can be involved in the pathophysiology of painful diabetic neuropathy. Patients suffering from vitamin D deficiency for any reason, develop insulin resistance which in turn leads to worsening symptoms related to nerve damage. It is advised that such patients receive vitamin D supplementation to not only prevent the progression of diabetic neuropathy but also reduce the severe pain associated with damage to the microvasculature.

References

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  2. Liu X, Xu Y, An M, Zeng Q. The risk factors for diabetic peripheral neuropathy: A meta-analysis. Plos One. 2019;14(2). doi:10.1371/journal.pone.0212574.
  3. Dyck PJ, Kratz KM, Karnes JL, Litchy WJ, Klein R, Pach JM, Wilson DM, O’Brien PC, Melton LJ. The prevalence by staged severity of various types of diabetic neuropathy, retinopathy, and nephropathy in a population‐based cohort. The Rochester Diabetic Neuropathy Study. 1993 Apr;43(4):817-24. doi:10.1212/wnl.43.4.817.
  4. Mathieu, C., Gysemans, C., Giulietti, A. et al. Vitamin D and diabetes. Diabetologia 48, 1247–1257 (2005). doi:10.1007/s00125-005-1802-7
  5. Martin T, Campbell KR. Vitamin D and Diabetes. Diabetes Spectrum 2011 May; 24(2): 113-118. doi:10.2337/diaspect.24.2.113
  6. Fukuoka M, Sakurai K, Ohta T, Kiyoki M, Katayama I. Tacalcitol, an active vitamin D3, induces nerve growth factor production in human epidermal keratinocytes. Skin Pharmacol Appl Skin Physiol. 2001;14(4):226-233. doi:10.7759/000056351
  7. Sugden JA, Davies JI, Witham MD, Morris AD, Struthers AD. Vitamin D improves endothelial function in patients with Type 2 diabetes mellitus and low vitamin D levels.  published: 27 February 2008. doi:10.111/j.1464-5491.2007.02360
  8. Alam U, Petropoulos LN, Ponirakis G, Ferdousi M, Asghar O, Jeziorska M, Marshall A, Boulton AJM, Efron N, Malik RA.  Vitamin D deficiency is associated with painful diabetic neuropathy. Diabetes Metab Res Rev. 2020;e3361. doi:10.1002/dmrr.3361
  9. Rhodes C. Vitamin D and Diabetic Peripheral Neuropathy: The Research Continues. Practical Pain Management. https://www.practicalpainmanagement.com/painful-diabetic-neuropathy-vitamin-D. Published May 19, 2020.
  10. Basit A, Basit KA, Fawwad A, Shaheen F, Fatima N, Petropoulos LN, Alam U, Malik RA. Vitamin D for the treatment of painful diabetic neuropathy. BMJ Open Diabetes Research and Care 2016;4:e000148. doi:10.1136/bmjdrc-2015- 000148

Electronic Supplementary Material

Acknowledgements

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