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长，仅在美国每年诊断出的新病例就超过 100 万例。尽管减肥已被证明可以成功地延缓糖尿病，但很难长期实现和维持。因此，迫切需要识别与体重无关的环境和易于改变的危险因素，以防止 t2DM 发病率的增加。根据动物和人类研究（包括我们自己的观察数据），维生素 D 和钙这两种营养因素被怀疑可以调节糖尿病风险。然而，我们对维生素 D 和钙对糖尿病风险的临床影响程度的认识存在重大差距，包括其与 2 型糖尿病相关的潜在生理作用机制的不确定性。目前，数据的缺乏限制了维生素 D 和钙作为预防 2 型糖尿病的可行营养干预措施的用途。该研究的中心假设是，维生素 D 和钙不足是 2 型糖尿病发生的危险因素，并且该风险是由胰腺 β 细胞功能、胰岛素敏感性和全身炎症的变化介导的。我们计划通过采用双重方法（观察研究和实验性人体试验）来检验我们的主要假设，以实现以下两个具体目标。 (1).在一项针对大型前瞻性队列（护士健康研究）的女性中进行的巢式病例对照研究设计中，评估维生素 D 状态与 2 型糖尿病风险之间关联的程度。目前的假设是，通过血清 25OHD 水平测量的维生素 D 状态与 2DM 风险呈负相关。该关联将被量化（2）。在一项为期 3 个月的随机安慰剂对照试验中，确定维生素 D 和钙补充剂对 β 细胞功能、胰岛素敏感性、葡萄糖耐量和全身炎症的影响，试验对象为患有 2 型糖尿病风险的成人，服用维生素 D3 和碳酸钙（2x2 析因设计）。工作假设是，补充维生素 D 和钙可以改善 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量（次要结果）。我们的研究结果将提供新颖且重要的数据，作为将这些营养素合理整合到传统医疗保健中以减轻 2 型糖尿病负担的基础。