Reduced vitamin D levels in painful diabetic peripheral neuropathy

Diabet Med. 2019 Jan;36(1):44-51. doi: 10.1111/dme.13798. Epub 2018 Sep 20.


Aim: Recent studies have reported an association between low vitamin D levels and diabetic peripheral neuropathy. However, many of these did not differentiate between people with painful diabetic peripheral neuropathy and those with painless diabetic peripheral neuropathy, or assess major confounding factors including sunlight exposure and daily activity. Our study addressed these limitations and evaluated vitamin D levels in people with carefully phenotyped diabetic peripheral neuropathy and controls.

Methods: Forty-five white Europeans with Type 2 diabetes and 14 healthy volunteers underwent clinical and neurophysiological assessments. People with Type 2 diabetes were then divided into three groups (17 with painful diabetic peripheral neuropathy, 14 with painless diabetic peripheral neuropathy and 14 with no diabetic peripheral neuropathy). All had seasonal sunlight exposure and daily activity measured, underwent a lower limb skin biopsy and had 25-hydroxyvitamin D measured during the summer months, July to September.

Results: After adjusting for age, BMI, activity score and sunlight exposure, 25-hydroxyvitamin D levels (nmol/l) (se) were significantly lower in people with painful diabetic peripheral neuropathy [painful diabetic peripheral neuropathy 34.9 (5.8), healthy volunteers 62.05 (6.7), no diabetic peripheral neuropathy 49.6 (6.1), painless diabetic peripheral neuropathy 53.1 (6.2); ANCOVAP = 0.03]. Direct logistic regression was used to assess the impact of seven independent variables on painful diabetic peripheral neuropathy. Vitamin D was the only independent variable to make a statistically significant contribution to the model with an inverted odds ratio of 1.11. Lower 25-hydroxyvitamin D levels also correlated with lower cold detection thresholds (r = 0.39, P = 0.02) and subepidermal nerve fibre densities (r = 0.42, P = 0.01).

Conclusions: We have demonstrated a significant difference in 25-hydroxyvitamin D levels in well-characterized people with painful diabetic peripheral neuropathy, while accounting for the main confounding factors. This suggests a possible role for vitamin D in the pathogenesis of painful diabetic peripheral neuropathy. Further prospective and intervention trials are required to prove causality between low vitamin D levels and painful diabetic peripheral neuropathy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Cross-Sectional Studies
  • Diabetes Mellitus, Type 2 / blood*
  • Diabetes Mellitus, Type 2 / complications*
  • Diabetes Mellitus, Type 2 / physiopathology
  • Diabetic Neuropathies / blood*
  • Diabetic Neuropathies / etiology*
  • Diabetic Neuropathies / physiopathology
  • Female
  • Healthy Volunteers
  • Humans
  • Male
  • Middle Aged
  • Neurologic Examination
  • Odds Ratio
  • Risk Factors
  • Vitamin D / analogs & derivatives*
  • Vitamin D / blood
  • Vitamin D Deficiency / blood*
  • Vitamin D Deficiency / complications*
  • Vitamin D Deficiency / physiopathology
  • White People


  • Vitamin D
  • 25-hydroxyvitamin D