Vitamin D and Diabetic Neuropathy

Abstract

Diabetes mellitus is a common group of metabolic disorders characterized by chronic hyperglycaemia as a result of insulin deficiency, insulin resistance or both. Peripheral neuropathies are the most common complication of diabetes mellitus affecting approximately 50% of patients with type 1 and type 2 diabetes and can also occur in subjects with impaired glucose tolerance (IGT). They include a heterogeneous group of neuropathies affecting sensory, motor and autonomic nerves and present with a range of clinical manifestation which can lead to pain, foot ulceration and amputation. Vitamin D deficiency is a major health problem affecting approximately 1 billion individuals worldwide and it has been linked with diabetic neuropathy. This research aimed to explore the molecular relationship between vitamin D and neuropathy in subjects with IGT and diabetes. 30 subjects with IGT, 43 type 1 diabetic patients (T1DM) with mild neuropathy, 12 T1DM with severe neuropathy and 26 healthy control subjects were studied. Circulating 25(OH)D level was measured and vitamin D receptor (VDR) expression in skin biopsies was assessed using immunohistochemistry. The intensity of immunostaining on the stratum basale, stratum spinosum, overall microvessels and on the endothelial cells and pericytes of the microvessels was semi-quantified. Plasma 25(OH)D levels (nmol/L) were globally reduced in subjects with IGT (54.03+/-5.51), T1DM with mild neuropathy (73.02+/-6.21), T1DM with severe neuropathy (56.85+/-12.64) and control subjects (55.06+/-10.03). There was a significant increase in VDR expression in IGT subjects compared to control subject on the overall microvessels (P=0.02), endothelium (P=0.02) and pericytes (P=0.02), but there was no difference on overall epidermis (P=0.19), stratum basale (P=0.20) and stratum spinosum (P=0.09). There was an increase in VDR expression in T1DM with mild neuropathy compared to controls on the epidermis (P=0.02), stratum basale (P=0.02), stratum spinosum (P=0.02), overall microvessels (P

Date of Award	31 Dec 2014
Original language	English
Awarding Institution	The University of Manchester
Supervisor	Rayaz Malik (Supervisor) & Maria Jeziorska (Supervisor)