Gender Associated with Neuropathic Pain — ADA 2019

New study findings challenge the link between neuropathic pain and vitamin D levels in people with type 2 diabetes.

Vitamin D deficiency is a common finding in people with type 2 diabetes. Neuropathic pain is a frequent complication of diabetes mellitus which is usually due to the toxic events of chronic hyperglycemia. Some study findings have found a relation between vitamin D deficiency in patients with type 2 diabetes and neuropathy; a recent study, conversely, demonstrates results that deny that association.

Vitamin D deficiency symptoms are similar to that of neuropathic pain (numbness, tingling, burning, impaired peripheral sensation and pain) and can be associated with the development of diabetes. The authors of the study reported that preliminary data showed that healthy vitamin D deficient people have had symptoms similar to that of neuropathy that has resolved by vitamin D supplementation. Therefore this study was conducted with an objective to test the hypothesis that vitamin D deficiency is associated with neuropathy in patients with type 2 diabetes, and aimed to find pain’s prevalence in patients with type 2 diabetes.

The study, “Neuropathic pain is not associated with serum vitamin D but is associated with female gender in patients with type 2 diabetes mellitus”, is a cross-sectional study conducted in Jordan, with 239 participants with type 2 diabetes enrolled between January and December 2017. Participants with chronic renal impairment and hepatic disease and/or who were on a recent supplement of vitamin D made up the exclusion criteria. PainDETECT, a questionnaire that uses a scale from 0 to 38 to define neuropathy, was used in the study. PainDETECT scores of 0 to 12 were considered nociceptive, scores 13 to 18 considered as having unclear neuropathy status (neuropathic pain can be present), and scores 19 to 38 considered as having neuropathic pain. Participants were classified as having deficient vitamin D level (<20ng/mL), insufficient vitamin D level (20-30ng/mL), or sufficient vitamin D level (>30ng/mL).

The study results reported that based on the questionnaire, 26.8% of the participants were classified as having neuropathic pain, 49% were nociceptive, and 24.3% had unclear neuropathy status. No significant difference was reported between participants classified as nociceptive, unclear neuropathy, or with neuropathy, in terms of serum vitamin D, fasting blood glucose, HbA1C, duration of type 2 diabetes, BMI, smoking status, and blood pressure. There was also no significant association between vitamin D status (deficient, insufficient, or sufficient) and neuropathy (P=0.55). Participants with unclear neuropathy had statistically significant higher age compared with nociceptive and neuropathic participants. 6.69% of participants (n=16) were treated for neuropathic pain with gabapentin and the study reported no association between vitamin D status and pain treatment.

The shocking finding of this study was that vitamin D deficiency was not associated with neuropathic pain, but gender was! The results reported that neuropathy score in females (76.6% of participants with neuropathy ³19) was significantly higher compared with the male participants (23.4%) (P<0.001) and female gender was the only statistically significant indicator for neuropathic pain in participants with type 2 diabetes.

 The authors of this study compared the study results to that of another, Ojo et al, where the PainDETECT questionnaire was also used to assess the prevalence of neuropathy among participants with type 2 diabetes. The results of the Ojo et al study also showed that neuropathic pain was more significant in females compared with males.

This study did not show any association between vitamin D levels and neuropathic pain in patients with type 2 diabetes, and these findings were inconsistent with the results of some other studies reported in the literature that used different assessment tools.

 In conclusion, this study did not report any significant association of vitamin D levels with neuropathic pain in patients with diabetes type 2, but reported significantly higher scores in females compared with the male participants

Practice Pearls:

• Vitamin D deficiency symptoms are similar to that of neuropathic pain and some previous study findings have reported a relation between vitamin D deficiency and neuropathy for people with diabetes.
• This study was conducted to determine whether vitamin D deficiency in patients with type 2 diabetes is associated with neuropathy and to find the prevalence of pain in this patient population. 
• The study findings reported no significant association in vitamin D levels and neuropathic pain in patients with type 2 diabetes. 
• Neuropathic scores in females were significantly higher compared with males with type 2 diabetes in this study.

Alkhatatbeh M, Abdul-Razzak KK. Neuropathic pain is not associated with serum vitamin D but is associated with female gender in patients with type 2 diabetes mellitus. BMJ Open Diab Res Care 2019;7:e000690. doi:10.1136/ bmjdrc-2019-000690

Ojo O, Odeniyi I, Iwuala S, et al. Frequency of neuropathic pain in type 2 diabetes mellitus at the Lagos university teaching hospital: a questionnaire-based outpatient survey. J Clin Sci 2016;13:46–50.

Marian Ayad, BSPharm, PharmD candidate, University of Colorado Skaggs School of Pharmacy and Pharmaceutical Sciences