Diabetes Prevention in the Vitamin D and Omega-3 Trial

描述（由申请人提供）：我们建议在nih资助的大规模随机试验维生素D和omega-3试验（VITAL）中评估维生素D3 （2,000 IU/天）和海洋omega-3脂肪酸（二十碳五烯酸[EPA] +二十二碳六烯酸[DHA]， 1g/天）补充剂在降低T2D风险方面的益处和风险平衡。VITAL试验是一项随机、双盲、安慰剂对照试验，旨在评估维生素D和海洋omega-3脂肪酸补充剂在2万名美国男性和女性中预防癌症和心血管疾病（CVD）的功效。我们将验证维生素D或omega-3补充剂在参与试验的非糖尿病受试者中降低T2D风险的假设。我们将进一步评估维生素D或omega-3补充剂是否以及在多大程度上改善葡萄糖耐量和胰岛素敏感性/分泌，在这些终点进行生物标志物评估的队列子集中。因此，我们提出了一种具有成本效益的策略来评估研究干预措施对糖尿病预防的有效性，并提供可能赋予这种益处的生理机制的详细特征。T2D事件的病例验证需要从病历审查和/或由参与者的医生完成的补充问卷中收集详细的诊断信息。为了补充病例验证，将通过将试验参与者与医疗保险和医疗补助服务中心（CMS）数据库连接来检索糖尿病诊断和降糖药物的其他数据。在我们的子研究中，在美国（波士顿、芝加哥、旧金山和休斯顿）的四个临床和转化科学中心（CTSC）招募了1000名基线时无糖尿病报告的参与者，他们将在基线（预随机化）和2年随访（按季节、按月匹配）时接受标准的2小时口服葡萄糖耐量试验（OGTT）。胰岛素和葡萄糖稳态的一系列测量将因此确定。糖化血红蛋白（HbA1c）也将被测量。总之，我们相信，母体VITAL试验的研究基础设施将为我们提供一个独特的、具有成本效益的机会，以回答有关维生素D或omega-3脂肪酸补充剂在预防T2D方面的潜在益处的重要问题，并识别潜在风险。在这项拟议的辅助研究中，我们请求资金在VITAL队列中进行糖尿病病例验证，并在基线和随访中进行一系列葡萄糖耐量测试。为了完成CTSC试验点参与者葡萄糖耐量的预随机化评估，至关重要的是，这项辅助研究必须与预定于2010年4月开始的母体VITAL试验的安慰剂“磨合”入组期同时进行。

DESCRIPTION (provided by applicant): We propose to evaluate the balance of benefits and risks of vitamin D3 (2,000 IU/day) and marine omega-3 fatty acid (eicosapentaenoic acid [EPA] + docosahexaenoic acid [DHA], 1g/day) supplements in reducing risk of T2D in the setting of an NIH-funded large-scale randomized trial, the VITamin D and OmegA-3 TriaL (VITAL). The VITAL trial is a randomized, double-blind, placebo-controlled trial specifically designed to evaluate the efficacy of vitamin D and marine omega-3 fatty acid supplements in the primary prevention of cancer and cardiovascular disease (CVD) among 20,000 U.S. men and women. We will test the hypothesis that vitamin D or omega-3 supplementation reduces the risk of T2D among initially non-diabetic subjects participating in the trial. We will further assess whether and to what extent vitamin D or omega-3 supplementation improves glucose tolerance and insulin sensitivity/secretion in a subset of the cohort undergoing biomarker evaluation for these endpoints. Hence, we propose a cost-effective strategy to evaluate the efficacy of the study interventions for diabetes prevention as well as to provide detailed characterization of the physiologic mechanisms that may impart this benefit. Case validation of incident T2D will require collection of detailed diagnostic information from medical record review and/or supplementary questionnaires completed by the participants' physicians. To complement case validation, additional data on diabetes diagnoses and hypoglycemic medication will be retrieved by linking the trial participants with the Centers for Medicare and Medicaid Services (CMS) database. In our substudy, 1,000 participants without a report of diabetes at baseline recruited at four Clinical and Translational Science Center (CTSC) sites across the U.S. (Boston, Chicago, San Francisco, and Houston) will undergo a standard 2-hour oral glucose tolerance test (OGTT) at baseline (pre- randomization) and at 2 years of follow-up (matched for season, by month). Serial measurements of insulin and glucose homeostasis will thereby be ascertained. Glycated hemoglobin A1c (HbA1c) will also be measured. In summary, we believe that the research infrastructure of the parent VITAL trial will offer us a unique cost-effective opportunity to answer important and timely questions about potential benefits of vitamin D or omega-3 fatty acid supplementation in the prevention of T2D, as well as to identify potential risks. In this proposed ancillary study, we request funds to perform diabetes case validation in the VITAL cohort and serial glucose tolerance testing at baseline and follow-up in a subsample. In order to complete pre-randomization assessment of glucose tolerance among participants at the CTSC sites, it is critically important that this ancillary study be undertaken parallel to the placebo "run-in" enrollment period for the parent VITAL trial, which is scheduled to begin in April 2010. PUBLIC HEALTH RELEVANCE: Existing biologic and observational evidence strongly supports potential health benefits of vitamin D and marine omega-3 fatty acids in preventing type 2 diabetes (T2D). However, due to lack of definitive data from large-scale clinical trials, it remains unclear whether T2D can be delayed or prevented by use of these supplements.