Vitamin D and type 2 diabetes (D2d)

描述（由申请人提供）：由于超过7900万美国人有患糖尿病的风险，预计糖尿病人口和相关费用将在未来25年翻一番。在试验中，以减肥为目标的生活方式改变成功地降低了患最常见的糖尿病——2型糖尿病（t2DM）的风险。然而，长期的体重维持在临床环境已被证明是难以捉摸的。重要的是，即使在成功减肥后，仍然存在大量的残余风险（~40-50%），并且可能归因于其他可改变的因素。一些用于治疗t2DM的药物也被研究用于预防t2DM，许多药物已被证明可以延缓糖尿病的发生；然而，药物治疗在糖尿病预防中的作用尚不清楚。因此，我们仍然迫切需要确定可改变的危险因素和安全、廉价和可接受的干预措施，以预防2型糖尿病和减少糖尿病相关疾病负担。根据最近发表的大量研究，维生素D已成为2型糖尿病（t2DM）风险的潜在决定因素。在纵向观察研究中，较高的维生素D水平与2型糖尿病风险降低高达83%相关。然而，支持补充维生素D预防2型糖尿病的证据仍然没有定论。在观察性研究中，维生素D水平与2型糖尿病风险之间的有利关联可能被多种因素所混淆。直接扩展我们之前的工作，本拨款申请中描述的研究目标是通过评估维生素D是否是预防高危人群2型糖尿病的有效干预措施来解决因果关系问题。我们建议开展维生素D和2型糖尿病（D2d）研究，这是一项多中心、随机、双盲、安慰剂对照、平行组一级预防临床试验，以评估维生素D补充的安全性及其对糖尿病前期参与者糖尿病发病时间的影响。最近的社论和评论已经认识到需要进行像D2d研究这样的试验，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之一，迫切需要进行严格的试验来确认观察和机制研究中看到的有希望的结果。因此，拟议的试验解决了一个重要而及时的问题，并有可能在临床上重要的t2DM预防领域产生重大影响，并直接影响公共卫生。该研究的潜在影响因高素质的研究人员组成的团队而增强，他们在开展以营养为基础的多中心试验方面具有互补的专业知识和经验，其中许多人以前曾合作过。

DESCRIPTION (provided by applicant): The diabetes population and related costs are expected to double in the next quarter century, as more than 79 million Americans are at risk of developing diabetes. In trials, lifestyle changes aimed at weight loss were successful at reducing risk of type 2 diabetes (t2DM), the most common type of diabetes. However, long-term weight maintenance in the clinical setting has proved elusive. Importantly, even after successful weight loss, substantial residual risk (~40-50%) remains and may be attributable to other modifiable factors. Several medications used to treat established t2DM have also been studied for t2DM prevention and many have been shown to delay incident diabetes; however, the role of pharmacotherapy for diabetes prevention is not clear. Therefore, there is a continued and pressing need for identification of modifiable risk factors and interventions that are safe, inexpensive and acceptable to prevent t2DM and decrease diabetes-related disease burden. Based on a large body of recently published studies, 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. Directly extending our prior work, the goal of the research described in this grant application is to address the issue of causality by evaluating whether vitamin D is an effective intervention for prevention of t2DM among high-risk individuals. We propose to conduct the vitamin D and type 2 diabetes (D2d) study, a multicenter, randomized, double-masked, placebo- controlled, parallel-group primary prevention clinical trial to evaluate the safety of vitamin D supplementation and its effect on the time to onset of diabetes in participants with pre-diabetes. The need for a trial such as the D2d study has been recognized in recent 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. The proposed trial, therefore, addresses an important and timely question and has the potential for significant impact in the clinically important area of t2DM prevention with direct public health implications. The potential impact of the study is heightened by the assembly of a team of highly qualified investigators with complementary expertise and experience in conducting nutrition-based multicenter trials, many of whom have worked together previously.