Editor: David L. Joffe, BSPharm, CDE, FACA
Author: Michael Zaccaro, Pharm. D. Candidate 2019, LECOM School of Pharmacy
Low levels thought to contribute to pathogenesis of painful diabetic peripheral neuropathy due to action on dorsal root ganglia.
It has been estimated that a quarter of all patients with diabetes suffer from a complication known as painful diabetic peripheral neuropathy. This condition is characterized by aching, burning, and/or electric shock-like sensations, which in many cases is consistent and unremitting. These sensations can result in contact hypersensitivity and insomnia, and can severely degrade quality of life. Painful diabetic peripheral neuropathy is typically treated with medications that alleviate the symptoms but do little to affect the progression or underlying pathology. It has been hypothesized that vitamin D levels may affect pain sensitivity in painful diabetic peripheral neuropathy due to its action on the dorsal root ganglia. Evidence from recent studies have suggested that an association between decreased levels of vitamin D and diabetic peripheral neuropathy might exist; however, findings have been inconsistent, and studies have been limited by their lack of consideration for confounding factors (not differentiating between diabetic peripheral neuropathy and painful diabetic peripheral neuropathy). Therefore, the aim of this study is to determine if an association exists between low vitamin D levels and painful diabetic peripheral neuropathy.
An observational study design was selected in order to determine if a correlation exists between vitamin D levels and painful diabetic peripheral neuropathy. Participants were recruited from the databases of the Sheffield Teaching Hospitals NHS Foundation Trust.
Patients were considered for inclusion if they were diagnosed with type 2 diabetes according to World Health Organization criteria. Patients were excluded if they had a history of neuropathies of non-diabetic origin, > 24 units of alcohol consumption per week, diabetic neuropathies other than diabetic peripheral neuropathy, or other systemic or neurological disorders. Once patients were deemed eligible, all participants were assessed for neuropathy via research-validated questionnaires (Douleur Neuropathique-4 questionnaire, Neuropathy Impairment Pain Symptom Inventory, and the sunlight exposure and activity questionnaire) as well as physical assessment (nerve conduction studies, sensory testing, cardiac autonomic function test, and laboratory analysis of vitamin D levels). Those with painful diabetic peripheral neuropathy were assessed with an additional research-validated questionnaire (Neuropathic Pain Symptom Inventory). One-way analysis of variance and analysis of covariance (ANOVA and ANCOVA) were used to determine statistical significance of means between groups and difference in vitamin D levels (considering sunlight exposure score, age, BMI, and activity score as covariates) between groups respectively.
A total of 49 individuals were deemed eligible and included in the study. All study participants were white, 14 did not have diabetes, 14 had a diagnosis of type 2 diabetes, 14 had painless diabetic peripheral neuropathy, and 17 had painful diabetic peripheral neuropathy. Once the data was analyzed, and adjusted for covariates, it was found that those with painful diabetic peripheral neuropathy had significantly lower levels of vitamin D (34.9 nmol/L) than those who did not have diabetes (62.05 nmol/L), those who had diabetes but without peripheral neuropathy (49.6 nmol/L), and those with non-painful diabetic peripheral neuropathy (53.1 nmol/L).
This study successfully addresses many of the shortcomings of previous studies on the same topic (i.e., ambiguously categorized participants, failing to account for confounding factors, etc.). The results suggest that there is an association between low vitamin D levels and painful diabetic peripheral neuropathy. While these findings seem to suggest that vitamin D levels may play a role in the pathogenesis of painful diabetic peripheral neuropathy, further research will be required in order to elucidate the clinical significance of these findings.
Practice Pearls: It is estimated that ¼ of all patients who have type 2 diabetes suffer from painful diabetic peripheral neuropathy, a condition characterized by aching, burning, and/or electric shock-like sensations, which may lead to decreased quality of life and disability.
It has been hypothesized that low vitamin D levels may contribute to the pathogenesis of painful diabetic peripheral neuropathy due to its action on the dorsal root ganglia.
This study indicates that an association exists between low vitamin D levels and occurrence of painful diabetic peripheral neuropathy; however, more study is required in order to determine the clinical significance of this finding.
Shillo, P., et al. “Reduced Vitamin D Levels in Painful Diabetic Peripheral Neuropathy.” Diabetic Medicine, 2018, doi:10.1111/dme.13798.
Michael Zaccaro, Pharm. D. Candidate 2019, LECOM School of Pharmacy
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