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

强心研究试图估计原住民心血管疾病的死亡率和发病率， 美国人与美国总人口的关系。他们报告说心血管疾病 亚利桑那州的美洲原住民人口的死亡率与美国的平均值相似（Lee等人， 1998年）。大多数种族的高血压患病率（美国心脏协会报告，2018年：非 西班牙裔白色，非西班牙裔黑人，墨西哥裔美国人）在过去几十年中普遍增加 （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--强调了 这一领域研究的重要性。高血压是最易改变和控制的危险因素之一 心血管疾病;然而，高血压发展的病因可能在以下方面不同： 种族群体。这可能会改变这些群体中成功的预防和治疗策略。 文献中一直有关于美洲原住民人群高胰岛素血症的报道， 假设当前研究先于以下发展：1）内皮功能障碍和2）血液 血压（BP）失调。事实证明，皮马印第安人对BP的监管方式不同， 比他们的高加索同行。皮马印第安人有较高的空腹胰岛素浓度，尽管正常 口服葡萄糖耐量试验高胰岛素血症也与标志物内皮功能障碍有关。 因此，高胰岛素浓度可能同时靶向与胰岛素分泌相关的两条途径。 该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，西班牙裔人口在我们的 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）（范围为7 - 75%）， 可以作为替代人口。本研究的目的是量化西班牙裔美国人的胰岛素状态， 不同比例的NAA，以确定其在内皮功能和BP调节中的作用。我们假设 具有较高NAA比例的西班牙裔人将：1）具有较高的胰岛素浓度比具有较低NAA比例的西班牙裔人高。 NAA的比例; 2）显示内皮功能受损;和3）显示对 高血压刺激。这个为期3年的项目将评估NAA，人体测量，胰岛素状态，血液 标记物、血管功能和BP反应。该团队包括一名具有DNA混合物专业知识的Co-I 分析，医生，内分泌学家，统计学家，研究生和本科生。结果 将提供深入了解BP失调发展中的种族特异性差异，并将告知 未来治疗策略。我们认为，有效的治疗将需要针对葡萄糖处理早期， 阻止导致失调的下游级联。

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.