Vitamin D for Type 2 Diabetes (D2D trial)

描述（由申请人提供）：根据我们小组和其他人最近的nih支持的人体研究，维生素D已成为2型糖尿病（t2DM）风险的潜在调节剂。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，支持一般补充维生素D的证据目前还不存在，因为维生素D水平与2型糖尿病之间的有利联系可能被各种因素所混淆，而且目前还没有专门设计的试验来测试维生素D对降低2型糖尿病风险的影响；因此，维生素D在预防2型糖尿病中的作用还不能得出明确的结论。这项应用扩展了我们之前的工作，并补充了我们在这一领域正在进行的工作，其目标是采取必要的下一步来解决因果关系问题，并量化维生素D对2型糖尿病风险的保护作用，如果存在的话。我们建议在美国几个有经验的临床站点进行一项多中心、随机、双盲、安慰剂对照试验，以评估维生素D是否能有效地干预高危人群预防2型糖尿病（维生素D和2型糖尿病，D2D试验）。拟议的D2D试验将在U01机制下进行，将是一项针对有2型糖尿病风险的成人的一级预防试验，以测试血浆25OHD浓度升高是否会延迟“糖尿病进展时间”。正如我们在拨款申请中所描述的那样，在最近的文献中已经认识到需要进行这样的试验。目前申请的是U34实施计划补助金，以规划拟议的研究。我们期望U34拨款的最终产品是及时提交申请（U01），以支持拟议的临床试验的进行。拟议的D2D试验在维生素D和t2DM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。我们期望研究结果能够明确改善维生素D状态在降低2型糖尿病风险中的作用。如果试验证实提高25OHD的有利/有害比，那么维生素D补充将被纳入常规医学方法，以预防2型糖尿病，并改善个人和社会的疾病负担。最后，该研究的影响由高素质的研究人员组成，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，这最大限度地提高了试验成功的可能性。

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.