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By Michael Rubin, MD
Professor of Clinical Neurology, Weill Cornell Medical College
Dr. Rubin reports no financial relationships relevant to this field of study.
SYNOPSIS: Vitamin D deficiency may exacerbate the clinical manifestations of diabetic neuropathy, and supplementation with vitamin D3 may be beneficial.
SOURCE: Alamdari A, et al. An inverse association between serum vitamin D levels with the presence and severity of impaired nerve conduction velocity and large fiber peripheral neuropathy in diabetic subjects. Neurol Sci 2015;36:1121-1126.
Skeletal manifestations of vitamin D deficiency include rickets and osteomalacia in children, and osteomalacia in adults. Approximately 3% of the human genome is under vitamin D control, and at least 10 extrarenal tissues express the enzyme 1-alpha-hydroxylase, responsible for converting vitamin D to its active form. Hence, it is not surprising that extraskeletal manifestations may also occur, including muscle weakness, cancer, hypertension, cardiovascular events, schizophrenia and depression, autoimmune disorders, type 1 diabetes, multiple sclerosis, and inflammatory bowel disease. Is there an independent association between vitamin D deficiency and diabetic neuropathy as defined by electrodiagnostic studies?
In this case-control study, patients newly diagnosed with type 2 diabetes were recruited from the Endocrinology and Metabolism Research Center, Vali-Asr Hospital, School of Medicine, Tehran University, Iran. Exclusionary criteria comprised type 1 diabetes, neuropathy of any cause other than diabetes, cancer, and thyroid, renal, or liver disease. Insulin-requiring diabetics were not included. Nerve conduction studies (NCS) were performed on all patients with neuropathic symptoms of numbness, tingling, or pain, and included the tibial, peroneal, median, and ulnar motor nerves, and median, ulnar, and sural sensory nerves. Statistical analysis comprised the t test for continuous variables, χ2 test for categorical variables, Pearson correlation coefficients, and two multivariate linear regression analyses, with two-sided P value < 0.05 considered significant.
Sixty-two diabetic patients were recruited: 29 with normal NCS and 33 with abnormal NCS. Both groups demonstrated a similar prevalence of retinopathy, microalbuminuria, and hypertension, and comparable HbA1c and creatinine levels. Serum vitamin D level was significantly lower in the abnormal NCS group, and correlated inversely with the degree of NCS abnormality, with lower vitamin D values present in those with more profound NCS abnormalities. For every 1 ng/mL increase in serum vitamin D, the presence and severity of NCS decreased by 2.2% and 3.4%, respectively. Lower vitamin D values correlate with worsening neuropathy in diabetic patients.
Can vitamin D supplementation improve symptomatic neuropathy in type 2 diabetic patients with vitamin D deficiency? Among 112 such patients enrolled in a prospective, placebo-controlled, clinical trial, 57 were given oral vitamin D3 (50,000 IU weekly for 8 weeks) and 55 received placebo. Exclusionary criteria included B12 deficiency, alcohol abuse, malignancy, autoimmune disease, hyperparathyroidism, and kidney or liver failure. Statistical analysis encompassed the χ2 test, Student t and Mann-Whitney U tests, and the Spearman correlation coefficient, with P < 0.05 considered significant. Using nerve conduction studies, a neuropathy symptom score, and a neuropathy disability score to assess the severity of diabetic peripheral neuropathy, vitamin D supplementation both increased serum vitamin D levels and significantly improved neuropathy symptom score values, though not neuropathy disability score nor nerve conduction studies.1 Neuropathic pain, particularly burning discomfort and hyperesthesia, was significantly improved. While awaiting confirmation from larger randomized, controlled trials, vitamin D supplementation can be a simple addition to the treatment of painful diabetic peripheral neuropathy.