Home / Resources / Articles / Vitamin D Deficiency and Diabetic Peripheral Neuropathy

Vitamin D Deficiency and Diabetic Peripheral Neuropathy

Nov 24, 2018
Editor: Joy Pape, MSN, FNP-C, CDE, WOCN, CFCN, FAADE

Author: Angela Reyes, Pharm.D. Candidate, LECOM College of Pharmacy

Patients with either painful or painless neuropathy found to have low vitamin D levels.

According to the American Diabetes Association, up to 50% of diabetic peripheral neuropathies may be asymptomatic. This is called painless neuropathy and patients with this type of neuropathy are at risk of injuries and diabetic foot ulcerations. Previous research studies linking vitamin D deficiency and diabetic peripheral neuropathy did not distinguish between painless and painful diabetic peripheral neuropathy. The following study focuses on these distinctions and other confounding factors like sunlight exposure and patient activity levels.


Research was done on 45 white Europeans with type 2 diabetes along with 14 participants without. Participants with diabetes were separated into 3 groups: 17 had painful diabetic neuropathy, 14 had painless diabetic neuropathy, and 14 had no neuropathy. From July to September, lower limb skin biopsies were taken to measure 25-hydroxyvitamin D levels. Small and large nerve fiber function was tested using quantitative sensory testing. Daily activity was also measured in all volunteers.

Results showed vitamin D levels were significantly lower in the group with diabetic peripheral neuropathy. The group with painful diabetic peripheral neuropathy had an average of 34.9 nmol/l of 25-hydroxyvitamin D compared to healthy participants who had 62.05 nmol/L. The painless diabetic neuropathy group had an average of 53.1 nmol/l of vitamin D. After adjusting for age, BMI, activity level, and sunlight exposure, vitamin D was the only significant independent variable with an odds ratio of 1.11. An ANCOVA model was used to analyze the data. Also, participants with lower vitamin D levels also had lower cold detection thresholds and lower subepidermal nerve fiber densities. These results suggest vitamin D could play a role in nociceptor generation, which contribute to the development of painful diabetic peripheral neuropathy.

Many patients with diabetes go undiagnosed and live in pain because neuropathy can get overlooked as a major complication of diabetes. Even worse, some patients are never treated for neuropathy because they experience no pain. These patients could develop diabetic foot ulcerations and not be able to feel it since the pain receptors have greatly diminished. Current medications to treat diabetic peripheral neuropathy are very limited. Medications work on only 1/3 of patients and really can only numb or block the pain. There are significant side effects to these medications as well. If vitamin D deficiency is linked to nociceptor generation, then it can be corrected at a cellular level and mitigate the development of peripheral neuropathy or at least alleviate the pain with little to no side effects. More research needs to be done in this area considering the small sample size of this study. This emerging area of research will help patients live longer and better lives with diabetes.

Practice Pearls:

  • Vitamin D deficiency is linked with painful and painless diabetic peripheral neuropathy despite age, BMI, activity level, or sun exposure.
  • Cold detection was lower in participants who were vitamin D deficient.
  • Educate patients on signs and symptoms of diabetic peripheral neuropathy and proactively screen for its development on patients who have diabetes.  


Shillo, D. Selvarajah, M. Greig, R. Gandhi, G. Rao, I. D. Wilkinson, P. and, S. Tesfaye. Reduced vitamin D levels in painful diabetic peripheral neuropathy. Diabetic Medicine.(2018): https://doi.org/10.1111/dme.13798

Rodica Pop-Busui, Andrew J.M. Boulton, Eva L. Feldman, Vera Bril, Roy Freeman, Rayaz A. Malik, Jay M. Sosenko, Dan Ziegler. Diabetic Neuropathy: A Position Statement by the American Diabetes Association. Diabetes Care.  40(1) (Jan 2017): 136-154; DOI: 10.2337/dc16-2042

Angela Reyes, Pharm.D. Candidate, LECOM College of Pharmacy