Patients with type 2 diabetes and painful diabetic peripheral neuropathy had significantly lower 25-hydroxyvitamin D levels compared with healthy volunteers and patients with type 2 diabetes without neuropathy or with painless neuropathy, according to data published in Diabetic Medicine.
“A number of recent studies have reported reduced vitamin D levels in diabetic peripheral neuropathy, although many of these did not assess major confounding factors, including seasonal sunlight exposure and daily activity,” Solomon Tesfaye, MB ChB, MD, FRCP, consultant physician/endocrinologist at Sheffield Teaching Hospitals and honorary professor of diabetic medicine at the University of Sheffield, and colleagues wrote in the study background. “There is some evidence, although not consistent, that vitamin D supplementation improves painful neuropathic symptoms, suggesting that vitamin D may have a role in the pathogenesis of painful diabetic peripheral neuropathy. Our study was designed to address these limitations.”
Researchers evaluated data from 59 people, including 14 healthy volunteers, 14 patients with type 2 diabetes without neuropathy, 14 patients with type 2 diabetes and painless diabetic peripheral neuropathy, and 17 patients with type 2 diabetes and painful diabetic peripheral neuropathy. Researchers recruited patients from the Sheffield Teaching Hospitals NHS Foundation Trust diabetes database and outpatient clinics from August 2013 to September 2014.
Patients with diabetic peripheral neuropathy had higher BMI (P = .02) and were older (P = .009) than the healthy volunteers and patients without neuropathy. Researchers found no significant differences between groups in estimates of sunlight exposure or outdoor activity. Patients with neuropathy had significantly higher scores on the Neuropathy Impairment Score Lower Limb and very low intra-epidermal nerve fiber density (P < .01).
Researchers adjusted for age, BMI, activity score and sunlight exposure and found significantly lower 25-hydroxyvitamin D levels in patients with painful diabetic peripheral neuropathy: 34.9 nmol/L compared with 62.05 nmol/L in healthy volunteers, 49.6 nmol/L in patients with type 2 diabetes and no peripheral neuropathy, and 53.1 nmol/L in patients with type 2 diabetes and painless diabetic peripheral neuropathy (P = .03).
Researchers then conducted a direct logistic regression analysis to assess the impact of seven independent variables on painful diabetic peripheral neuropathy: age, BMI, sunlight exposure score, activity score, diabetes duration, mean arterial blood pressure and vitamin D levels. The analysis revealed that vitamin D was the only independent variable that statistically significantly contributed to the model (inverted OR = 1.11).
“This suggests that for each unit reduction in vitamin D, the odds of painful diabetic peripheral neuropathy increased by a factor of 1.11,” the researchers wrote.
Data also revealed a significant negative correlation between vitamin D levels and pain scores (P = .02), but no significant correlation between vitamin D levels and nerve conduction studies. Lower 25-hydroxyvitamin D levels were also associated with lower cold detection thresholds (P = .02) and subepidermal nerve fiber densities (P = .01). Researchers also evaluated the relationship between vitamin D levels and HbA1c and found a significant negative correlation with higher glucose load associated with lower vitamin D levels (P = .01), which they said suggests a possible mechanistic link between diabetes, vitamin D and neuropathy.
“Further long-term prospective cohort or interventional studies are required to examine causality (ie, if low serum vitamin D levels cause painful diabetic peripheral neuropathy or if they are a risk factor/surrogate marker for the development of painful diabetic peripheral neuropathy),” the researchers wrote. “If causality is confirmed, this will have a significant impact on clinical practice as there would be a clear rationale for early screening and treatment for low vitamin D in people with painful diabetic neuropathy.”
The study was funded by Sheffield Teaching Hospitals NHS Trust, charitable fund. The authors report no relevant financial disclosures.