Several studies have been conducted to investigate the relation between 25-hydroxyvitamin D [25(OH)D] level and diabetic neuropathy (DN). However, there is still no clear conclusion due to differences in study design and cut-off values used in the published work, in addition to the absence of a comprehensive meta-analysis (MA) on the topic. The present systematic review and MA therefore aims at clarifying the association between vitamin D level and peripheral DN in patients with type 2 diabetes mellitus. Primary research studies that explored the association between 25(OH)D level and diabetic peripheral neuropathy in type 2 diabetes were located from Medline, EMBASE, Web of Science, Cochrane Library, CINHAL and Google Scholar. Twenty-six studies met the inclusion criteria with 6277 participants where 2218 were diabetic with DN, 2959 were diabetic without DN and 406 were healthy. Diabetic patients with DN showed significantly lower serum 25(OH)D compared with patients without DN (standardised mean difference (SMD) of −0·92 (95 % CI −1·18, −0·65, I2 = 93·3 %, P < 0·0001). The pooled OR value of vitamin D deficiency was higher in patients with DN, 1·84 (95 % CI 1·46, 2·33, P < 0·0001) and 2·87 (95 % CI 1·10, 7·52, P = 0·03) when using fixed-effects and random-effects models, respectively. Vitamin D deficiency has been found to be highly prevalent among diabetic patients with neuropathy. Since 25(OH)D has been implicated in glucose haemostasis and showed benefit in reducing neuropathy symptoms, its supplementation is warranted for this population of patients.

Peripheral sensory and autonomic neurons are known to possess insulin receptors. These have been considered to be of the peripheral type, i.e. similar to those of hepatic and fat cells rather than of the brain type which show dual specificity for both insulin and insulin-like growth factor (IGF-1). We have examined the localisation of insulin and IGF-1 receptors in cultured sensory and sympathetic ganglion cells using confocal microscopy and indirect labelling with FITC (fluorescein isothiocyanate) and TRITC (tetramethyl rhodamine isothiocyanate) respectively. We have shown that in cultured U266B1 multiple myeloma cells these receptors display separate localisation, whereas they are colocalised in IM-9 lymphocytes which are known to possess hybrid receptors. We have confirmed the sequestration of insulin and IGF-1 receptors in the cytoplasm of sensory and sympathetic neurons, consistent with a brain-type receptor. The colocalisation of insulin and IGF-1 receptors in sensory and sympathetic ganglion cells is consistent with the view that they are hybrid receptors, similar to those present in the CNS. The function of these receptors, as suggested for the CNS, may be related to trophic support for neurons.