Vitamin D and Calcium Homeostasis in Relation to Type 2 Diabetes

维生素 D 和钙稳态与 2 型糖尿病的关系

• 批准号: 7135280
• 负责人: Anastassios G Pittas
• 金额: $ 35.9万
• 依托单位: TUFTS MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-09-30 至 2011-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7135280
• 关键词: calcium; clinical research; clinical trials; diet therapy; dietary supplements; disease /disorder prevention /control; female; glucose tolerance; homeostasis; human subject; human therapy evaluation; insulin sensitivity /resistance; noninsulin dependent diabetes mellitus; pancreatic islets; patient oriented research; questionnaires; vitamin D

DESCRIPTION (provided by applicant): The incidence of type 2 Diabetes Mellitus (t2DM) is increasing at an alarming rate both nationally and worldwide with more than 1 million new cases per year diagnosed in the US alone. Although weight- loss has been shown to be successful in delaying diabetes, it is difficult to achieve and maintain long- term. Therefore, identification of weight-independent environmental and easily modified risk factors is urgently needed to prevent the increase in the incidence of t2DM. Vitamin D and calcium are two nutritional factors that have been suspected as modifiers of diabetes risk based on animal and human studies including our own observational data. However, there are critical gaps in our knowledge about the magnitude of the clinical effect of vitamin D and calcium on diabetes risk, including uncertainty about their potential physiologic mechanism of action in relation to t2DM. Currently, this lack of data limits the usefulness of vitamin D and calcium as feasible nutritional interventions for prevention of t2DM. The central hypothesis of the proposed study is that, vitamin D and calcium insufficiency are risk factors for the development of t2DM and that the risk is mediated by changes in pancreatic beta- cell function, insulin sensitivity, and systemic inflammation. We plan to test our main hypothesis by pursuing a dual approach (observational study and experimental human trial) to achieve the following 2 specific aims. (1). Assess the magnitude of the association between vitamin D status and risk of t2DM in a nested case-control study design in women in a large prospective cohort, the Nurses' Health Study. The working hypothesis is that vitamin D status, as measured by serum 25OHD level, is inversely associated with t2DM risk. The association will be quantified (2). Determine the effects of vitamin D and Calcium supplementation on beta-cell function, insulin sensitivity, glucose tolerance and systemic inflammation in a 3-month randomized placebo-controlled trial of adults at risk for t2DM given vitamin D3 and calcium carbonate (2x2 factorial design). The working hypothesis is that vitamin D and calcium supplementation improves beta-cell function and insulin sensitivity (primary outcomes) and systemic inflammation and glucose tolerance (secondary outcomes). Our results will provide novel and important data that will serve as the foundation for the rational integration of these nutrients into conventional medical care to ameliorate t2DM burden.

描述（由申请人提供）：2型糖尿病（T2DM）的发病率在全国和全球范围内以惊人的速度增加，仅在美国就被诊断出了100万个新病例。尽管已经证明体重损失在延迟糖尿病方面取得了成功，但很难实现和维持长期。因此，迫切需要确定不依赖重量的环境和易于修改的风险因素，以防止T2DM的发生率增加。维生素D和钙是两个营养因素，这些因素被认为是基于动物和人类研究（包括我们自己的观察数据）的糖尿病风险的修饰剂。但是，我们的知识存在关键的差距，即维生素D和钙对糖尿病风险的临床作用的大小，包括有关其潜在的与T2DM相关的潜在生理作用机理的不确定性。目前，缺乏数据限制了维生素D和钙作为预防T2DM的可行营养干预措施的有用性。拟议研究的中心假设是，维生素D和钙功能不全是T2DM发展的危险因素，并且风险是由胰腺β-细胞功能，胰岛素敏感性和全身性炎症的变化所介导的。我们计划通过采用双重方法（观察性研究和实验人类试验）来测试我们的主要假设，以实现以下两个特定目标。 （1）。评估在嵌套的病例对照研究设计中，在大型前瞻性队列中，在嵌套的病例对照研究设计中，维生素D状况与T2DM的风险之间的关联程度。工作假设是，通过血清25OHD水平衡量的维生素D状态与T2DM风险成反比。协会将进行量化（2）。确定维生素D和钙补充对β细胞功能，胰岛素敏感性，葡萄糖耐受性和全身性炎症的影响，在3个月的随机安慰剂对照试验中，对维生素D3和碳酸盐钙化钙的T2DM风险的成人试验（2X2偏病设计）。工作假设是，维生素D和钙补充剂可提高β细胞功能和胰岛素敏感性（主要结果）以及全身炎症和葡萄糖耐受性（次要结果）。我们的结果将提供新颖而重要的数据，这些数据将成为将这些营养素合理整合到常规医疗保健中以减轻T2DM负担的基础。