title: Vitamin D and Diabetic Complications: True or False Prophet?
abstract: Vitamin D deficiency is now recognized as a condition of increasing prevalence worldwide. Vitamin D has an established role in calcium and bone metabolism; however, more recently associations with vitamin D deficiency and risk of developing diabetes, diabetes complications, and cardiovascular disease have all been acknowledged. The vitamin D receptor is ubiquitously expressed, and experimental, in vitro, and in vivo studies strongly suggest a role in regulating the transcription of multiple genes beyond calcium homeostasis. These include antiproliferative, immunomodulatory, angiogenic, inhibition of the renin-angiotensin-aldosterone system, and neurotrophic factor expression. Observational studies report a strong association between vitamin D deficiency and cardiovascular and metabolic disorders; however, there remains a paucity of large long-term randomized clinical trials showing a benefit with treatment. An increasing body of literature suggests a possible pathogenetic role of vitamin D in the long-term complications of diabetes and vitamin D deficiency may also exacerbate symptoms of painful diabetic peripheral neuropathy. It remains unknown if supplementation of vitamin D to normal or non-deficient levels alters pathogenetic processes related to diabetic microvascular complications. With the high prevalence of vitamin D deficiency in patients with diabetes and putative mechanisms linking vitamin D deficiency to diabetic complications, there is a compelling argument for undertaking large well-designed randomized controlled trials of vitamin D supplementation.
authors.affiliation: Centre for Endocrinology and Diabetes, Institute of Human Development, University of Manchester and the Manchester Royal Infirmary, Central Manchester Hospital Foundation Trust, Manchester, UK. uazman.alam@manchester.ac.uk.
authors.forename: Uazman
authors.initials: U
authors.lastname: Alam
authors.affiliation: Centre for Endocrinology and Diabetes, Institute of Human Development, University of Manchester and the Manchester Royal Infirmary, Central Manchester Hospital Foundation Trust, Manchester, UK.
authors.forename: Vilashini
authors.initials: V
authors.lastname: Arul-Devah
authors.affiliation: Centre for Endocrinology and Diabetes, Institute of Human Development, University of Manchester and the Manchester Royal Infirmary, Central Manchester Hospital Foundation Trust, Manchester, UK.
authors.forename: Saad
authors.initials: S
authors.lastname: Javed
authors.affiliation: Centre for Endocrinology and Diabetes, Institute of Human Development, University of Manchester and the Manchester Royal Infirmary, Central Manchester Hospital Foundation Trust, Manchester, UK.|Weill Cornell Medicine-Qatar, Qatar Foundation, Doha, Qatar.
authors.forename: Rayaz A
authors.initials: RA
authors.lastname: Malik
keywords: Cardiovascular disease; Diabetic nephropathy; Diabetic neuropathy; Diabetic retinopathy; Pain; RAAS inhibition; Vitamin D