Vitamin D for Type 2 Diabetes (D2D trial)

描述（由申请人提供）：根据我们小组最近NIH支持的人体研究和其他人的工作，维生素D已成为2型糖尿病（t2 DM）风险的潜在调节剂。在纵向观察性研究中，较高的维生素D状态与T2 DM风险降低高达83%相关。然而，目前尚不存在支持一般补充的证据，因为维生素D状态与2型糖尿病之间的有利关联可能受到多种因素的混淆，并且没有专门设计用于测试维生素D对降低2型糖尿病风险的影响的已发表试验;因此，无法得出关于维生素D预防2型糖尿病的作用的明确结论。本申请的目的是扩展我们以前的工作，并补充我们在这一领域正在进行的工作，采取必要的下一步措施来解决因果关系问题，并量化维生素D在2型糖尿病风险中的保护作用（如果存在）。我们提出了一项多中心、随机、双盲、安慰剂对照试验，在美国几个有经验的临床研究中心进行，以评估维生素D是否是预防高危人群中2型糖尿病的有效干预措施（维生素D和2型糖尿病，D2 D试验）。拟议的D2 D试验将在U 01机制下进行，将是一项针对有2型糖尿病风险的成年人的一级预防试验，以测试血浆25 OHD浓度升高是否会延迟糖尿病进展时间。正如我们在资助申请中所描述的那样，最近的文献已经认识到需要进行这样的试验。本申请是一个U34实施规划补助金计划拟议的研究。我们希望U34资助的最终产品是及时提交申请（U 01），以支持拟议临床试验的开展。拟议的D2 D试验在维生素D和T2 DM预防的临床重要领域具有很高的潜在影响，具有广泛的公共卫生意义。我们希望研究结果能够确定改善维生素D状态在改变2型糖尿病风险中的作用。如果试验证实提高25 OHD的有利利益/危害比，那么维生素D补充剂将被整合到传统的医疗方法中，以预防2型糖尿病并减轻个人和社会的疾病负担。最后，由高素质的研究人员组成的团队在运行基于营养的多中心试验方面具有互补的专业知识和经验，其中许多人以前曾在一起工作，这最大限度地提高了试验成功的可能性，从而提高了研究的影响力。 公共卫生相关性：研究涉及与NIDDK和ODS相关的重要健康问题。维生素D缺乏症和2型糖尿病在美国非常普遍，因此，考虑到其广泛的适用性，特别是考虑到与治疗2型糖尿病及其并发症的慢性期相比，补充或强化维生素D的成本相对便宜，所提出的研究具有潜在的高影响。我们期待拟议试验的研究结果，该试验将测试维生素D和2型糖尿病之间是否存在因果关系，以确定优化维生素D状态在改变2型糖尿病风险中的作用。如果该试验证实维生素D对2型糖尿病风险的有利益处/危害比，那么维生素D补充剂将被整合到传统的医疗方法中，以预防超过5000万有患2型糖尿病风险的美国人患2型糖尿病。

DESCRIPTION (provided by applicant): Based on recent NIH-supported human studies from our group and work from others, vitamin D has emerged as a potential modifier of type 2 diabetes (t2DM) risk. In longitudinal observational studies, higher vitamin D status is associated with up to 83% reduction in the risk of t2DM. However, the evidence to support general supplementation does not currently exist because the favorable association between vitamin D status and t2DM may be confounded by a variety of factors and there are no published trials specifically designed to test the effects of vitamin D on reducing t2DM risk; therefore, definitive conclusions cannot be drawn on the role of vitamin D for prevention of t2DM. The goal of this application, which extends our previous work and complements our ongoing work in this area, is to take the necessary next step to address the issue of causality and to quantify the protective benefit of vitamin D in t2DM risk, if present. We propose a multi-center, randomized, double-masked, placebo-controlled trial to be conducted among several experienced clinical sites across the U.S. to evaluate whether vitamin D is an effective intervention for prevention of t2DM among high- risk individuals (vitamin D and type 2 Diabetes, D2D trial). The proposed D2D trial, which will be conducted under the U01 mechanism, will be a primary prevention trial of adults at risk for t2DM, to test whether raising plasma 25OHD concentration delays 'time-to-diabetes- progression". The need for such a trial has been recognized in the recent literature, as we describe in the grant application. The present application is for a U34 Implementation Planning grant to plan the proposed study. We expect the final product of the U34 grant to be the timely submission of an application (U01) to support the conduct of the proposed clinical trial. The proposed D2D trial has a high potential impact in the clinically important areas of vitamin D and t2DM prevention with extensive public health implications. We expect study results to define the role of improving vitamin D status in modifying t2DM risk. If the trial confirms a favorable benefit/harm ratio of raising 25OHD, then vitamin D supplementation will be integrated into conventional medical approaches to prevent t2DM and ameliorate personal and societal disease burden. Finally, the impact of the study is heightened by the assembled team of highly qualified investigators with complementary expertise and experience in running nutrition-based multicenter trials, many of whom have worked together previously, which maximizes the likelihood of trial conduct success. PUBLIC HEALTH RELEVANCE: The research addresses important health issues of relevance to NIDDK and ODS. Vitamin D deficiency and type 2 diabetes are highly prevalent in the U.S., and therefore the proposed study is of potential high impact given its broad applicability, especially given that the cost of supplementation or fortification with vitamin D is relatively inexpensive compared to treating the chronic phase of type 2 diabetes and its complications. We expect study results of the proposed trial, which will test whether a causal link between vitamin D and type 2 diabetes exists, to define the role of optimizing vitamin D status in modifying risk of type 2 diabetes. If the trial confirms a favorable benefit/harm ratio of vitamin D on type 2 diabetes risk, then vitamin D supplementation will be integrated into conventional medical approaches to prevent type 2 diabetes in the more than 50 million Americans who are at risk of developing type 2 diabetes.