Vitamin D for Type 2 Diabetes (D2D trial)

描述(由申请人提供)：基于我们小组最近由NIH支持的人类研究和其他人的工作，维生素D已经成为2型糖尿病(T2 DM)风险的潜在修饰物。在纵向观察性研究中，较高的维生素D水平与T2 DM风险降低高达83%相关。然而，目前还不存在支持一般补充剂的证据，因为维生素D状态和T2 DM之间的有利联系可能会被各种因素混淆，而且还没有专门设计的试验来测试维生素D对降低T2 DM风险的效果；因此，无法就维生素D在预防T2 DM方面的作用得出明确的结论。这项申请的目标是扩展我们之前的工作，并补充我们在这一领域正在进行的工作，目的是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T2 DM风险中的保护益处(如果存在)。我们建议进行一项多中心、随机、双盲、安慰剂对照试验，在全美几个经验丰富的临床地点中进行，以评估维生素D是否是预防高危人群中T2 DM的有效干预措施(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T2 DM高危成年人的一级预防试验，以测试提高血浆25OHD浓度是否会延缓糖尿病的进展时间。正如我们在拨款申请中所描述的那样，最近的文献已经认识到这样一项试验的必要性。目前申请的是U34实施规划补助金，以规划拟议的研究。我们预计U34拨款的最终结果将是及时提交一份申请(U01)，以支持拟议临床试验的进行。拟议的D2D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影响。我们期待研究结果明确改善维生素D状况在降低T2 DM风险中的作用。如果试验证实了提高25OHD的有利益处/危害比，那么维生素D补充剂将被整合到传统医学方法中，以预防T2 DM并减轻个人和社会疾病负担。最后，由高度合格的研究人员组成的团队加强了研究的影响，这些研究人员在运行基于营养的多中心试验方面拥有互补的专业知识和经验，其中许多人以前曾合作过，这最大限度地增加了试验成功的可能性。 公共卫生相关性：这项研究涉及与NIDDK和消耗臭氧层物质相关的重要健康问题。维生素D缺乏和2型糖尿病在美国非常普遍，因此这项拟议的研究具有潜在的重大影响，因为它具有广泛的适用性，特别是考虑到与治疗慢性2型糖尿病及其并发症相比，补充或强化维生素D的成本相对较低。我们期待拟议的试验的研究结果，该试验将测试维生素D和2型糖尿病之间是否存在因果联系，以确定优化维生素D状态在改变2型糖尿病风险方面的作用。如果试验证实维生素D对2型糖尿病风险的有益/有害比率是有利的，那么维生素D补充剂将被整合到传统的医学方法中，以预防5000多万有患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.