A randomised controlled trial of high dose vitamin D in recent-onset type 2 diabetes
Introduction
With few dietary sources of vitamin D, sufficiency of this pluripotent steroid depends on its synthesis in the skin in response to ultraviolet B radiation. Indoor lifestyles and active protection against sun exposure have contributed to an increased prevalence of vitamin D insufficiency, even in sun-abundant countries [1]. Emerging evidence suggests that vitamin D insufficiency may be a risk factor for both type 1 and type 2 diabetes [2], [3], [4] and associated with reduced beta-cell function in type 2 diabetes (reviewed in Ref. [3]). Pancreatic beta cells not only express the nuclear vitamin D receptor (VDR) [5] but also 1-alpha-hydroxylase which converts 25-hydroxyvitamin D (25D3) to the active metabolite 1,25-dihydroxyvitamin D3 (1,25D3) [6]. Vitamin D supplementation may promote beta-cell function [3], [7] by a direct effect on insulin secretion or beta-cell survival, or by an indirect effect to inhibit production of inflammatory cytokines that impair beta-cell function [8] and induce beta-cell apoptosis [9]. Despite indications that vitamin D insufficiency may increase the risk of type 2 diabetes [3], [4], the potential therapeutic effect of vitamin D has not been widely tested in randomised controlled trials. We aimed to determine if high dose oral vitamin D3 supplementation improves beta-cell function and glycaemic indices in recent-onset type 2 diabetes.
Section snippets
Participants
A randomised, double blind placebo-controlled clinical trial of oral vitamin D3 (D) was conducted in 50 Caucasians sequentially diagnosed with type 2 diabetes. Participants gave written informed consent and the study was approved by the Royal Melbourne Hospital Human Research Ethics Committee. Participants were recruited from the community through a national diabetes register (National Diabetes Services Scheme, Australia). They were eligible for enrolment if they had diabetes diagnosed
Recruitment
Of the 50 participants, 26 were randomly allocated to the D group and 24 to placebo, with males and females being equally represented. Only 3 required modification of their diabetes therapy due to hyperglycaemia during the trial, with one requiring insulin. There were no adverse events related to the study treatments, in particular no participant developed hypercalcemia. Similar numbers of D and placebo participants were enrolled in all seasons. Randomisation commenced in January 2008 and the
Discussion
High dose D supplementation substantially increased both 25D and 1,25D concentrations without toxicity. It has been shown previously that oral D increases serum 25D in people with diabetes [8], [15], [16], [17], but its effect on serum 1,25D has not been reported. The significant increase in 1,25D in response to oral D challenges the traditional view that 1,25D production is tightly regulated by renal 1-alpha hydroxylase to maintain calcium homeostasis. It indicates that oral D has broader
Funding
This work was funded by grants from The Munro Foundation, Melbourne, and Diabetes Australia Research Trust, and supported by Victorian State Government Operational Infrastructure Support and Australian Government NHMRC IRIIS. SE was a Postgraduate Scholar of the National Health and Medical Research Council of Australia (NHMRC) and received a Basser Family Scholarship from the Royal Australasian College of Physicians. LCH is a Senior Principal Research Fellow of the NHMRC.
Conflict of interest statement
There is no conflict of interest for any of the authors.
Contribution statement
Study concept and design LCH, SF, SE; acquisition of data: SE, NM, PGC, JMW; analysis and interpretation of data: SE, SF, TS, LCH; drafting of manuscript SE, SF, LCH.
Acknowledgements
The authors thank Diabetes Australia for assistance in recruiting participants and Professor John Wark and Dr Mark Stein, Royal Melbourne Hospital, for advice on vitamin D dosing and comments on the manuscript.
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2017, Journal of Diabetes and its ComplicationsCitation Excerpt :We identified a total of 2341 articles from PubMed and Cochrane Central prior to July 1st 2016. After excluding 216 duplicates and studies that did not fulfill the inclusion criteria, 29 articles remained for our systematic review, of which 22 articles had sufficient baseline and outcome data for meta-analysis (Fig. 1).16–44 We also searched the clinicaltrials.gov database and performed hand searches and did not find any additional studies for this review.