The Role of Vitamin D in Established Type 2 Diabetes

描述（由申请人提供）：糖尿病的发病率正在以惊人的速度增长，无论是在国内还是在世界范围内，每年仅在美国就诊断出大约200万新病例，其中近10例新病例中有9例是由于2型糖尿病（t2DM）。由于超过8000万美国人有患2型糖尿病的风险，预计糖尿病人口和相关费用在未来25年将至少翻一番。在临床试验中，药物治疗作为生活方式改变的调整已经成功地治疗了2型糖尿病，尽管依从性往往很差，药物相关的成本正在上升；因此，迫切需要确定可在公共卫生层面应用的替代治疗方案，以减少2型糖尿病相关负担。根据美国国立卫生研究院（nih）资助的研究，我们和其他研究人员发现，维生素D水平不佳是导致2型糖尿病病理生理的潜在因素。然而，由于观察性研究中存在潜在的混淆，并且缺乏针对血糖和其他代谢结果设计的足够有力的试验数据，维生素D是否在t2DM患者中具有临床作用尚不清楚。新研究者R01的续期申请的目标是评估维生素D是否有效，这直接扩展了我们在第一个资助周期中在该领域开展的工作

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.