SLR - June 2022 - Shane Sato, DPM
Reference: Putz Z, Tordai D, Hajdú N, Vági OE, Kempler M, Békeffy M, Körei AE, Istenes I, Horváth V, Stoian AP, Rizzo M, Papanas N, Kempler P. Vitamin D in the Prevention and Treatment of Diabetic Neuropathy. Clin Ther. 2022 Apr 12:S0149-2918(22)00136-9Level of Evidence: III
Scientific Literature Review
Reviewed By: Shane Sato, DPM
Residency Program: Cambridge Health Alliance - Cambridge, MA
Podiatric relevance: Diabetic polyneuropathy (DPN) is the most common neuropathy in developed countries. Approximately 50 percent of patients with diabetes will eventually develop neuropathy. Chronic kidney disease, older age, and obesity are among the many risk factors for developing vitamin D deficiency. Many of which diabetic patients have. There is a growing body of evidence that vitamin D deficiency might have an effect on the development of diabetic sensory motor neuropathy, in particular painful diabetic neuropathy.
Methods: A PubMed database search was performed for papers published through September 2021 using the key words vitamin D, diabetes, diabetes mellitus, diabetic neuropathy, polyneuropathy, peripheral neuropathy, cardiac autonomic neuropathy, supplementation, and therapy. Only articles available in English were considered.
Results: A total of 13 articles were included which investigated the relationship between serum vitamin D and diabetic neuropathy. Several studies examined the relationship between a low vitamin D level and neuropathy but the exact underlying mechanisms are still not fully understood. Vitamin D receptors (VDR) can be found in the cytoplasm and nuclei in cells throughout the nervous system. VDR have been associated with several diseases in addition to diabetic neuropathy, such as neurodegenerative and autoimmune diseases. Vitamin D stimulates the production of nerve growth factor (NGF). Treatment of NGF deficient diabetic rats with vitamin D has been associated with increased NGF production, with an apparent preventive effect on neurotrophic deficit. Several studies found that vitamin D deficiency (<20 ng/ml) is an independent risk factor for DPN. High dose vitamin D supplementation was associated with reduced serum proinflammatory IL-6 and increased serum anti-inflammatory IL-10 concentrations and these effects were related to improvements in severity of DPN and skin microcirculation. The prevalence of severe vitamin D deficiency (<10 ng/ml) was also found to be significantly greater in diabetic patients with an ulcer compared to those without. Cardiovascular autonomic neuropathy (CAN) may increase the risk of cardiovascular-related mortality. There is an association with serum levels of vitamin D and measures of CAN. Data shows that a very high and very low level of vitamin D is related to CAN in patients with type 1 diabetes mellitus and type 2 diabetes mellitus. Mortality rate was also analyzed in patients who had vitamin D measurements from the national registry of deaths in Austria. They found that adults with vitamin D deficiency were more likely to have died from complications of diabetes during 10 year follow-up compared with vitamin D sufficient patients.
Conclusion: There is data to suggest that vitamin D is a risk factor for the development of painful diabetic neuropathy and that treatment of vitamin D deficient diabetics with high dose vitamin D can be beneficial. Vitamin D therapy could be a reliable option for treating patients with diabetic complications, more specifically neuropathy, however, further studies are needed to confirm these notions.