The Role of Vitamin D in Established Type 2 Diabetes

描述（由申请人提供）：糖尿病的发病率在全国和全球范围内以惊人的速度增加，仅在美国每年就有约200万例新确诊病例，其中近9/10的新病例是由于2型糖尿病（t2 DM）。预计在下一个世纪，糖尿病人口和相关费用将至少翻一番，因为超过8000万美国人有患2型糖尿病的风险。在临床试验中，药物治疗作为对生活方式改变的调整已成功用于治疗2型糖尿病，但依从性往往较差，药物相关费用不断上升;因此，迫切需要确定可在公共卫生层面应用的替代治疗选择，以减少2型糖尿病相关负担。根据NIH资助的研究，我们的小组和其他人，次优的维生素D状态已成为2型糖尿病的病理生理学的潜在贡献者。然而，由于观察性研究中的潜在混杂因素，以及缺乏针对血糖和其他代谢结局设计的充分把握度试验的数据，目前尚不清楚维生素D是否在确诊的2型糖尿病患者中具有临床作用。新研究者R 01的更新申请的目的是直接扩展我们在第一个资助周期期间进行的该领域的工作，以评估维生素D是否 有效的非药物营养干预T2 DM。中心假设是，在t2 DM中，维生素D状态不佳，通过补充维生素D提高25 OHD浓度，通过改善胰岛素分泌和敏感性，改善确诊的t2 DM患者的胰岛素和其他代谢结果。次要假设是维生素D的作用被特定的维生素D受体（VDR）多态性改变。我们计划通过在已确诊的轻度/中度2型糖尿病患者中进行为期1年的维生素D3补充剂随机、双盲、安慰剂对照试验，检验我们的中心假设并实现本申请的目标。维生素D状态下降是我们改变生活方式的结果，在调整其他生活方式因素后，维生素D状态与2型糖尿病密切相关（体重、饮食），这使得拟议的研究非常重要和及时，也符合国家的研究重点，因为该研究有望填补一个基本的知识空白，这加剧了目前关于维生素D补充剂建议的激烈争议。用于非骨骼疾病。

DESCRIPTION (provided by applicant): The incidence of diabetes is increasing at an alarming rate both nationally and worldwide with approximately two million new cases diagnosed every year in the US alone, with nearly 9 out of 10 new cases due to type 2 diabetes melitus (t2DM). Diabetes population and related costs are expected to at least double in the next quarter century, as more than 80 million Americans are at risk of developing t2DM. In clinical trials, pharmacotherapy as an adjust to lifestyle changes has been successful for treating t2DM, nonetheless adherence is often poor and drug-related costs are escalating; therefore, identification of alternative therapeutic options that can be applied at the public healh level is urgently needed to decrease t2DM-related burden. Based on NIH-funded research from our group and others, suboptimal vitamin D status has emerged as a potential contributor to the pathophysiology of t2DM. However, because of potential confounding in observational studies and lack of data from adequately powered trials designed for glycemic and other metabolic outcomes, it remains unclear whether vitamin D has a clinical role in patients with established t2DM. The goal of this renewal application for a New Investigator R01, which directly extends our work in this area conducted during the first funding cycle, is to evaluate whether vitamin D is an effective non-pharmacologic nutritional intervention for t2DM. The central hypothesis is that suboptimal vitamin D status worsens glycemia in t2DM and that raising one's 25OHD concentration with vitamin D supplementation improves glycemia and other metabolic outcomes in patients with established t2DM, through improvements in insulin secretion and sensitivity. A secondary hypothesis is that the effect of vitamin D is modified by specific Vitamin D Receptor (VDR) polymorphisms. We plan to test our central hypothesis and accomplish the goals of this application by conducting a 1-year long randomized, double-masked, placebo-controlled trial of vitamin D3 supplementation in persons with established t2DM of mild/moderate severity. Declining vitamin D status is a consequence of our altered lifestyle and its strong association with t2DM, after adjusting for other lifestyle factors (weight, diet), makes the proposed study very important and timely and also consistent with national research priorities as the study is expected to fill a fundamental knowledge gap which fuels the current intense controversy in relation to the development of recommendations for vitamin D supplementation for non-skeletal medical conditions.