Diabetes Prevention in the Vitamin D and Omega-3 Trial

描述(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)的背景下，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。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对癌症和心血管疾病(CVD)的一级预防作用。我们将测试这样一种假设，即补充维生素D或omega-3可以降低参与试验的最初非糖尿病受试者的T2D风险。我们将进一步评估补充维生素D或omega-3是否以及在多大程度上改善正在接受这些终点生物标记物评估的队列的子集的葡萄糖耐量和胰岛素敏感性/分泌。因此，我们提出了一种经济有效的策略来评估糖尿病预防研究干预措施的有效性，并提供可能带来这一好处的生理机制的详细特征。T2D事件的病例验证将需要从参与者的医生填写的医疗记录审查和/或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)数据库联系起来，检索有关糖尿病诊断和降血糖药物的更多数据。在我们的子研究中，在美国四个临床和翻译科学中心(CTSC)(波士顿、芝加哥、旧金山和休斯顿)招募的1000名没有糖尿病基线报告的参与者将在基线(随机前)和两年的随访期(按季节、按月匹配)接受标准的2小时口服葡萄糖耐量试验(OGTT)。因此，胰岛素和葡萄糖动态平衡的系列测量将被确定。糖化血红蛋白A1c(HbA1c)也将被测量。总而言之，我们相信Parent 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，以回答有关补充维生素D或omega-3脂肪酸在预防T2D方面的潜在益处的重要和及时的问题，以及识别潜在的风险。在这项拟议的辅助研究中，我们申请资金在重要队列中进行糖尿病病例验证，并在基线时进行系列糖耐量测试，并在子样本中进行随访。为了完成CTSC站点参与者中葡萄糖耐量的预随机化评估，这项辅助研究必须与定于2010年4月开始的Parent VITAL试验的安慰剂“磨合”阶段同时进行，这一点至关重要。 公共卫生相关性：现有的生物和观察证据有力地支持维生素D和海洋omega-3脂肪酸在预防2型糖尿病(T2D)方面潜在的健康益处。然而，由于缺乏来自大规模临床试验的明确数据，目前尚不清楚使用这些补充剂是否可以推迟或预防T2D。

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.