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Vitamin D Deficiency Linked to Painful Diabetic Neuropathy

Sep 15, 2020
Editor: David L. Joffe, BSPharm, CDE, FACA

Author: Brianna Belton, PharmD. Candidate, Florida Agricultural & Mechanical University, College of Pharmacy and Pharmaceutical Sciences 

As patients’ vitamin D levels rose, the pain and other symptoms of painful diabetic neuropathy decreased. 

Diabetic neuropathy, or nerve damage, is a common complication associated with diabetes. Symptoms range from numbness and pain in extremities to decreased functioning of internal organs. Painful diabetic neuropathy is associated with sleep disturbances and reduced quality of life. Currently, it is unknown how exactly diabetes causes damage to the nerves, but there are a few contributing factors that are known. One includes vitamin D deficiency. Vitamin D deficiency is highly prevalent in patients with diabetes. Patients with diabetes and low vitamin D levels are also at higher risk of experiencing diabetic neuropathy with pain. 


Previous studies have shown a significant association of vitamin D deficiency with neuropathy and symptoms. Results have shown that treating the deficiency led to decreased pain based on pain scores and symptoms. As the vitamin D levels rose, the pain and symptoms decreased, and the quality of life improved.  

In this study, Vitamin D Deficiency Is Associated with Painful Diabetic Neuropathy, 43 patients with type 1 diabetes were divided into two groups: painless diabetic peripheral neuropathy (n=20) or painful diabetic peripheral neuropathy (n=23). There were 14 healthy patients without diabetes that were used as the control subjects. To compare these groups, many factors were assessed including neurologic deficits, quantitative sensory testing (QST), electrophysiology, skin biopsy, corneal confocal microscopy (CCM), and measurement of serum 25(O.H.)D. The severity of painful neuropathy was also assessed with the use of the neuropathy symptom profile (NSP) and the McGill Visual Analogue Score (McGill VAS). Vitamin D levels were based on both deficiency (< 20 ng/mL) and insufficiency (< 30 ng/mL). 

There were no significant differences displayed between many of the factors analyzed. However, symptoms based on the NSP were significantly higher in the painful neuropathy group compared with the painless group (p < 0.0005) and control group (p < 0.0001). Both positive (hyperalgesia and allodynia, p = 0.009) and negative (paresthesia and numbness, p = 0.02) symptoms of diabetic neuropathy were greater among the patients with painful neuropathy. Additionally, serum 25(OH)D levels were significantly lower among the patients with painful neuropathy (24.0 ± 14.1 ng/mL) compared with the patients without pain (34.6 ± 15.0 ng/mL, p = 0.01) and the control subjects (34.1 ± 8.6 ng/mL, p = 0.03). The odds ratio in favor of painful diabetic neuropathy was 9.8 [95% CI 2.2 – 76.4; p = 0.003] for vitamin D deficiency and 4.4 [95% CI 1.1 – 19.8; p = 0.03] for vitamin D insufficiency. 

The authors of this study suggest that vitamin D deficiency and insufficiency are associated with painful diabetic neuropathy.  Previous studies have demonstrated the relationship between vitamin D deficiency and diabetic neuropathy, but not painful diabetic neuropathy. This study was an effort to analyze a potential cause of diabetic neuropathy being that the exact etiology is not clear. 

This study included only a small group of subjects. With a small sample size, more studies will have to be conducted to ensure that the results are precise and reliable. Additionally, clinical trials should be performed to be able to control the variables, like sunlight exposure, and even to figure out treatment for the patients with low vitamin D levels. The study also included only patients with type 1 diabetes. Patients with type 2 diabetes should also be included because of the high prevalence and different pathophysiologies between the two types of diabetes. Lastly, the study did not include patients with diabetes but without neuropathy. Assessing the vitamin D levels in these patients is relevant to determine further the link between vitamin D deficiency and diabetic neuropathy.  

Practice Pearls: 

  • The etiology of painful diabetic neuropathy is not currently known. However, vitamin D levels have been linked painful diabetic neuropathy. 
  • This small study compared patients with type 1 diabetes, with and without pain with their diabetic neuropathy, to healthy patients without diabetes. 
  • Patients with higher pain levels associated with their diabetic neuropathy also had significantly lower serum 25(O.H.)D levels. 
  • Vitamin D deficiency and insufficiency are associated with painful diabetic neuropathy. 


Alam, U., Petropoulos, I. N., Ponirakis, G., Ferdousi, M., Asghar, O., Jeziorska, M., . . . Malik, R. A. (2020). Vitamin D deficiency is associated with painful diabetic neuropathy. Diabetes/Metabolism Research and Reviews. doi:10.1002/dmrr.3361 


Brianna Belton, PharmD. Candidate, Florida Agricultural & Mechanical University, College of Pharmacy and Pharmaceutical Sciences