vitamin D Status, Cardiovascular Health and Diabetes in American Indians

由于21世纪的生活方式和低饮食摄入量，维生素D水平低下是地方性疾病。一个不断增长的身体 的数据表明，维生素D水平低与非肌肉骨骼疾病的风险增加有关； 值得注意的是，心血管疾病和II型糖尿病。心血管疾病，针对哪种类型的2 糖尿病是一个主要的风险因素，在美国超过三分之一的死亡是由糖尿病引起的。美国印第安人是 与非西班牙裔白人相比，他们更容易患上心血管疾病和糖尿病。事实上, 五大湖地区的美洲印第安人的糖尿病发病率在全国排名第三 年龄调整后的糖尿病死亡率几乎是所有种族死亡率的三倍， 全美印第安人心血管疾病发病率最高。在这个人口中， 心血管疾病和糖尿病是四大死因中的两个，我们的初步工作 发现低维生素D状态很常见。 我们的基本假设是低维生素D状态与心血管疾病有因果关系 产生一种细胞因子介导的促炎环境，导致内皮功能障碍，并最终 动脉粥样硬化症。我们进一步假设，这种促炎状态会导致各种其他 不利的健康后果，包括胰岛素敏感性受损和最终的2型糖尿病。它 因此，补充维生素D应该会减少炎症，从而恢复内皮功能 和葡萄糖动态平衡，从而降低心血管疾病和糖尿病的风险。 这项研究的具体目的是：评估维生素D状态与 内皮功能；评估维生素D对内皮细胞功能障碍的影响是否与促炎有关 并探讨维生素D状态与血糖稳态参数的关系。 在这项研究中，100名年龄在70岁以下的绝经后女性没有糖尿病或已知 心血管疾病将被随机分配接受维生素D3，要么是目前标准的摄入量 每日400次，或估计达到最佳状态的剂量，2500次，连续6个月。我们将定义 维生素D状态和随后对补充的反应对动脉内皮功能的影响 僵硬、血浆炎症标志物和血糖动态平衡。

Low vitamin D status is endemic due to 21st century lifestyle and low dietary intake. An increasing body of data relates low vitamin D status to increased risk for non-musculoskeletal morbidities; including, most notably, cardiovascular disease and type II diabetes mellitus. Cardiovascular disease, for which type 2 diabetes mellitus is a major risk factor, causes over one-third of all deaths in the US. American Indians are more likely to develop cardiovascular disease and diabetes mellitus than non-Hispanic whites. In fact, American Indians of the Great Lakes Region have the third highest diabetes mellitus rate in the nation, an age-adjusted diabetes mellitus mortality rate almost three-fold higher than the all-race mortality and the highest rates of cardiovascular disease among American Indians nationally. In this population, where cardiovascular disease and diabetes mellitus are two of the top four causes of death, our preliminary work finds low vitamin D status commonplace. Our fundamental hypothesis is that low vitamin D status is causally related to cardiovascular disease by producing a cytokine mediated pro-inflammatory milieu that leads to endothelial dysfunction and ultimately to atherosclerotic disease. We further hypothesize that this pro-inflammatory state leads to a variety of other adverse health outcomes including impaired insulin sensitivity and ultimately type 2 diabetes mellitus. It follows that that vitamin D supplementation should reduce inflammation, thus restoring endothelial function and glucose homeostasis, thereby reducing cardiovascular disease and diabetes mellitus risk. The specific aims of this study are: to evaluate the relationships between vitamin D status and endothelial function; to assess if vitamin D effects on endothelial dysfunction are related to a proinflammatory milieu and to explore relationships of vitamin D status with parameters of glucose homeostasis. In this study, 100 postmenopausal Al women up to age 70 years without diabetes mellitus or known cardiovascular disease will be randomly assigned to receive vitamin D3, either the current standard intake of 400 ID or a dose estimated to achieve optimal status, 2,500 ID, daily for six months. We will define the effects of vitamin D status, and subsequent response to supplementation, on endothelial function, arterial stiffness, plasma markers of inflammation and glucose homeostasis.