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The influence of Native American ancestry in Hispanics in northern Arizona: an investigation of insulin in endothelial function and blood pressure regulation

美洲原住民血统对亚利桑那州北部西班牙裔的影响：胰岛素在内皮功能和血压调节中的研究

基本信息

批准号：
10045258
负责人：
Sara Sun Jarvis
金额：
$ 45.01万
依托单位：
NORTHERN ARIZONA UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-08-03 至 2024-07-31
项目状态：
已结题

项目摘要

The Strong Heart Study sought to estimate cardiovascular disease mortality and morbidity among Native Americans in relation to the general United States population. They reported that cardiovascular disease mortality rates in the Native American populations in Arizona were similar to the US averages (Lee et al., 1998). The prevalence of hypertension in most races (reported by American Heart Association, 2018: non- Hispanic white, non-Hispanic black, Mexican American) has generally increased over the past few decades (Benjamin et al., 2018). One group remains unreported or underreported—Native Americans—underscoring the importance of research in this area. Hypertension is one of the most modifiable and controllable risk factors for cardiovascular disease; however, the etiology of the development of hypertension may vary between racial groups. This may modify successful prevention and treatment strategies in these groups. Hyperinsulinemia in Native American populations has been consistently reported in the literature and is hypothesized for the current study to precede the development of: 1) endothelial dysfunction and 2) blood pressure (BP) dysregulation in this group. It has been demonstrated that Pima Indians regulate BP differently than their Caucasian counterparts. Pima Indians had higher fasting insulin concentrations, despite a normal oral glucose tolerance test. Hyperinsulinemia has also been associated with markers endothelial dysfunction. Thus, it is possible that high insulin concentration concomitantly targets two pathways associated with the increased risk for hypertension and cardiovascular events in this population. The Native American population is difficult to assess in a research setting due to historical reasons. However, the Hispanic population in our region in AZ has been reported to possess high levels of Native American ancestry (NAA) (range 7-75%) and may serve as a surrogate population. The purpose of this study is to quantify insulin status in Hispanics of varying proportions of NAA to determine its role in endothelial function and BP regulation. We hypothesize that Hispanics with higher proportions of NAA will: 1) possess higher insulin concentrations than those with lower proportions of NAA; 2) demonstrate impaired endothelial function; and 3) demonstrate greater BP reactivity to hypertensive stimuli. This 3-yr project will assess NAA, anthropometric measurements, insulin status, blood markers, blood vessel function, and BP responses. The team includes a Co-I with expertise in DNA admixture analysis, a physician, an endocrinologist, a statistician, and graduate and undergraduate students. The results will provide insight into the race-specific differences in the development of BP dysregulation and will inform future treatment strategies. We surmise that effective treatment will need to target glucose handling early to stop the downstream cascade leading to dysregulation.

强心研究试图估计土著居民心血管疾病的死亡率和发病率美国人与普通美国人的关系。他们报告说，心血管疾病亚利桑那州美洲原住民人口的死亡率与美国平均水平相似(Lee等人， 1998年)。大多数种族中高血压的患病率(美国心脏协会报告，2018年：非西班牙裔白人、非西班牙裔黑人、墨西哥裔美国人)在过去几十年里普遍增加 (Benjamin等人，2018年)。有一个群体仍然没有被报道或被低估-美洲原住民-强调这方面研究的重要性。高血压是最易改变和最可控的危险因素之一。对于心血管疾病；然而，高血压的病因可能不同于种族团体。这可能会改变这些群体中成功的预防和治疗策略。美洲原住民人群中的高胰岛素血症在文献中一直有报道，而且目前研究的假设是：1)内皮功能障碍和2)血液压力(BP)失调在本组。已经证明，皮马印第安人对BP的监管是不同的比他们的高加索同行更多。皮马印第安人的空腹胰岛素浓度更高，尽管正常口服葡萄糖耐量试验。高胰岛素血症也与标记物内皮功能障碍有关。因此，高胰岛素浓度有可能同时针对与在这一人群中高血压和心血管事件的风险增加。美洲原住民人口是由于历史原因，很难在研究环境中进行评估。然而，我们国家的拉美裔人口据报道，亚利桑那州的一个地区拥有高水平的美洲原住民血统(NAA)(范围7-75%)和可以作为代孕种群。这项研究的目的是量化#年西班牙裔美国人的胰岛素状况。不同比例的NAA，以确定其在内皮功能和血压调节中的作用。我们假设 NAA比例较高的拉美裔人将：1)胰岛素浓度高于那些NAA比例较低的人 NAA的比例；2)显示内皮功能受损；以及3)显示更强的BP反应性高血压刺激物。这个为期3年的项目将评估NAA、人体测量、胰岛素状况、血液标记物、血管功能和血压反应。该团队包括一名在DNA混合物方面拥有专业知识的Co-I 分析，一个内科医生，一个内分泌学家，一个统计学家，以及研究生和本科生。结果是将深入了解BP失调发展过程中特定种族的差异，并将告知未来的治疗策略。我们推测，有效的治疗需要及早针对血糖的处理阻止导致失调的下游瀑布。