The developed countries have a high incidence of diabetic polyneuropathy which is reported in 10–50% of patients with diabetes. At the time of diagnosis, neuropathy is present in 10% of diabetic patients and overall in 50% of patients with a 25-year history of the disease [3]. Hypovitaminosis D is highly prevalent in patients with Type 2 diabetes and could be a precursor to the development of diabetic neuropathy by causing neurotrophic deficits. First, the β-cell in the pancreas that secretes insulin has been shown to contain VDRs as well as the 1 alpha-hydroxylase enzyme. Vitamin D deficiency leads to reduced insulin secretion and is known to increase the levels of parathyroid hormone. Additionally, Vitamin D contributes to the normalization of extracellular calcium, ensuring normal calcium flux through cell membranes; therefore, low vitamin D may diminish calcium’s ability to affect insulin secretion. This in turn has been linked to increased insulin resistance, which is associated with diabetes, hypertension, inflammation, and increased cardiovascular risk [4].  

Evidence indicates that vitamin D treatment improves glucose tolerance and insulin resistance. Supplementation with vitamin D has been shown to restore insulin secretion in animals. Researchers have found an indirect effect on insulin secretion, potentially by a calcium effect on insulin secretion. Other potential mechanisms associated with vitamin D and diabetes include improving insulin action by stimulating expression of the insulin receptor, enhancing insulin responsiveness for glucose transport, having an indirect effect on insulin action potentially via a calcium effect on insulin secretion, and improving systemic inflammation by a direct effect on cytokines [5]. One study on research that showed vitamin D-associated improvements in axon regeneration and myelination following nerve injury, as well as increases in nerve growth factor synthesis and prevention of neuronal degeneration [6].   Furthermore, another potential positive effect of Vitamin D is that it may favorably alter coronary calcification, which is a precursor of vascular events and a common finding in Type 2 diabetes [7]. Derangements in vitamin D levels have been shown to contribute to insulin resistance through several mechanisms. This in turn has led to painful diabetic neuropathy. Vitamin D insufficiency is associated with self‐reported peripheral neuropathy symptoms even after adjusting for demographic factors, obesity, co‐morbidities, use of medications for neuropathy and diabetes duration, and control [8].  Vitamin D supplementation could further add value to the treatment of painful peripheral diabetic neuropathy [9]. A single high-dose of intramuscular vitamin D appears to be a safe and effective treatment for PDN [10].