Vitamin D and Type 2 Diabetes (D2d)

项目总结/摘要 基于大量的证据，维生素D已成为2型糖尿病的潜在决定因素 （T2DM）风险。在纵向观察研究中，较高的维生素D水平与高达83%的 降低T2DM的风险。然而，支持补充维生素D预防糖尿病的证据 T2DM仍无定论。维生素D状态与观察性2型糖尿病风险之间的有利关联 研究可能会受到各种因素的混淆，长期、设计良好和有充分把握度的试验 缺乏。 “维生素D和2型糖尿病”（D2d）研究由NIH资助，以提供明确的结论 补充维生素D对预防2型糖尿病的作用。D2d是一项正在进行的多中心， 一项随机（1：1）、双盲、安慰剂对照、平行组、一级预防临床试验， 组（口服4，000 IU/天维生素D3与安慰剂）中有糖尿病风险的参与者， 治疗糖尿病D2D被设计为事件驱动的试验。该研究在12月达到了招募目标 2016年，98%的入组受试者在平均随访19个月后继续D2d。遵守 研究药丸的比例非常高（> 92%的药丸处方）。更新补助金的主要目的是继续遵循- D2d人群（N = 2，423），并根据方案完成研究， 经DSMB和所有参与IRB批准，以回答研究的主要问题：每日口服 维生素D3补充剂降低了美国糖尿病高危成年人的糖尿病发病风险？ 次要目的将评估：维生素D补充剂对事件的治疗效果的异质性 由关键基线特征定义的亚组中的糖尿病（例如，血液25-羟基维生素D浓度）， 对次要结果的影响（例如，血压），以及4000 IU/天的长期安全性和耐受性 维生素D3补充剂最后，来自D2d安慰剂组的数据将定义预- 糖尿病使用新的美国糖尿病协会诊断标准，包括血红蛋白A1c。 多篇社论和评论已经认识到需要进行D2d研究等试验，包括 2011年医学研究所关于维生素D膳食参考摄入量的报告，该报告将糖尿病确定为 最有希望的非骨骼结果，迫切需要严格进行试验，以确认 在观察和机制研究中看到了有希望的结果。

Project Summary / Abstract Based on a large body of evidence, vitamin D has emerged as a potential determinant of type 2 diabetes (t2DM) risk. In longitudinal observational studies, higher vitamin D status was associated with up to 83% reduction in the risk of t2DM. However, the evidence to support vitamin D supplementation for prevention of t2DM remains inconclusive. The favorable association between vitamin D status and t2DM risk in observational studies may be confounded by a variety of factors, and long-term, well-designed and adequately powered trials are lacking. The “Vitamin D and type 2 diabetes” (D2d) study is being funded by NIH to provide definitive conclusions regarding the role of vitamin D supplementation for prevention of t2DM. D2d is an ongoing, multicenter, randomized (1:1), double-masked, placebo-controlled, parallel-group, primary prevention clinical trial with two groups (oral 4,000 IU/day of vitamin D3 vs. placebo) among participants at risk for diabetes who are followed for incident diabetes. D2d is designed as an event-driven trial. The study met its enrollment goal in December 2016 and 98% of enrolled participants continue in D2d after a mean follow-up of 19 months. Adherence to study pills is very high (>92% of pills prescribed). The primary aim of the renewal grant is to continue follow- up of the D2d population (N=2,423) and complete the study according to the protocol, which has been approved by the DSMB and all participating IRBs, to answer the study’s primary question: does oral daily vitamin D3 supplementation lower risk of incident diabetes among U.S. adults at high risk for diabetes? Secondary Aims will assess: the heterogeneity of treatment effect of vitamin D supplementation on incident diabetes in subgroups defined by key baseline characteristics (e.g., blood 25-hydroxyvitamin D concentration), effects on secondary outcomes (e.g., blood pressure), and the long-term safety and tolerability of 4000 IU/day of vitamin D3 supplementation. Finally, data from the D2d placebo group will define the natural history of pre- diabetes using the new American Diabetes Association diagnostic criteria that include hemoglobin A1c. The need for a trial such as the D2d study has been recognized in multiple editorials and reviews, including the 2011 Institute of Medicine report on dietary reference intakes for vitamin D, which identified diabetes as one of the most promising non-skeletal outcomes with an urgent need for rigorously conducted trials to confirm the promising results seen in observational and mechanistic studies.