Heart Disease Risk Factors In African Americans

非裔美国人的心脏病危险因素

• 批准号: 7152649
• 负责人: Anne E Sumner
• 金额: --
• 依托单位: NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/7152649
• 关键词: African American; body composition; cardiovascular disorder risk; caucasian American; clinical research; computed axial tomography; diabetes mellitus; fatty acid metabolism; free fatty acids; gender difference; glucose tolerance; glucose tolerance test; hormone regulation /control mechanism; human subject; insulin sensitivity /resistance; mathematical model; obesity; photon absorptiometry; racial /ethnic difference; triglycerides

Obesity, diabetes and heart disease are characterized by resistance to insulin as a glucoregulatory hormone. African Americans, particularly African American women, suffer disproportionately from these conditions. We believe that African American women may have increased sensitivity to insulin?s ability to suppress lipolysis and this contributes to their accelerated development of obesity and related complications. The hypothesis of this research is that African American men are resistant to insulin as a glucoregulatory hormone and resistant to insulin as a fat regulatory hormone. In contrast, African American women are resistant to insulin as a glucoregulatory hormone but sensitive to insulin as a fat regulatory hormone. The frequently sampled intravenous glucose tolerance test is used to measure insulin?s action as a glucoregulatory hormone. Unfortunately there is no index of insulin?s action as a fat regulatory hormone. Hence we are working on the development of this index by obtaining free fatty acids during the frequently sampled glucose tolerance test. Our goal is be able to do one test to obtain information about both actions of insulin. However, the development of an index of free fatty acid sensitivity to insulin during the frequently sampled intravenous glucose tolerance test involves sophisticated mathematical modeling and will need to be validated. As we work towards developing this index, we have studied sex differences in triglyceride (TG) levels as well as body fat content and distribution in African Americans. We have found that TG levels are lower in African Americans than what is reported for Caucasians. Further TG levels are lower in African American women than men. One reason for this sex difference could be sex differences in body fat distribution. We determined using serial slice computerized tomographic scans from the iliac crest to the dome of the diaphragm that African American women have lower visceral fat volumes than men. As visceral fat is a major source of free fatty acids used to synthesize TG, this could be one reason for sex differences in TG levels. We also found that the activity of lipoprotein lipase (LPL), the enzyme responsible for clearing TG from the circulation, is not impaired in the presence of insulin resistance. Therefore even in the presence of insulin resistance African Americans are able to effectively clear TG from the circulation. While there was no sex difference in either the level of LPL activity or the effect of insulin resistance, the inability of insulin resistance to compromise LPL activity may contribute to why African Americans have lower TG levels than Caucasians. This is because in Caucasians, insulin resistance leads to a clear impairment of LPL activity and higher TG levels. Further, the lack of an effect on LPL activity may explain our additional finding, that unlike in Caucasians, TG levels cannot be used a marker of insulin resistance in African Americans.

肥胖、糖尿病和心脏病的特征在于对作为葡萄糖调节激素的胰岛素的抵抗。非裔美国人，特别是非裔美国妇女，不成比例地患有这些疾病。我们认为，非洲裔美国妇女可能对胰岛素的敏感性增加？的能力，抑制脂肪分解，这有助于他们的肥胖和相关并发症的加速发展。这项研究的假设是，非洲裔美国人对胰岛素作为葡萄糖调节激素和胰岛素作为脂肪调节激素有抵抗力。相比之下，非裔美国妇女对胰岛素作为葡萄糖调节激素有抵抗力，但对胰岛素作为脂肪调节激素敏感。频繁采样的静脉葡萄糖耐量试验用于测量胰岛素？作为一种糖调节激素的作用。不幸的是没有胰岛素的指数？作为脂肪调节激素的作用。因此，我们正在通过在频繁采样的葡萄糖耐量试验中获得游离脂肪酸来开发该指数。我们的目标是能够做一个测试，以获得有关胰岛素两种作用的信息。然而，在频繁采样的静脉内葡萄糖耐量试验期间游离脂肪酸对胰岛素敏感性的指数的开发涉及复杂的数学建模，并且需要进行验证。当我们致力于开发这一指数时，我们研究了非裔美国人甘油三酯（TG）水平以及体脂含量和分布的性别差异。我们已经发现，TG水平是在非洲裔美国人低于什么是高加索人的报告。此外，非裔美国女性的TG水平低于男性。这种性别差异的一个原因可能是身体脂肪分布的性别差异。我们使用连续切片计算机断层扫描从髂嵴到横膈膜的圆顶，非洲裔美国妇女有较低的内脏脂肪体积比男性。由于内脏脂肪是用于合成TG的游离脂肪酸的主要来源，这可能是TG水平性别差异的原因之一。我们还发现，脂蛋白脂酶（LPL）的活性，负责清除TG从循环中，在胰岛素抵抗的存在下不受损害。因此，即使在存在胰岛素抵抗的情况下，非洲裔美国人也能够有效地从循环中清除TG。虽然在LPL活性水平或胰岛素抵抗的影响方面没有性别差异，但胰岛素抵抗无法损害LPL活性可能有助于非洲裔美国人的TG水平低于白人。这是因为在白种人中，胰岛素抵抗导致LPL活性明显受损和较高的TG水平。此外，缺乏对LPL活性的影响可以解释我们的额外发现，即与高加索人不同，TG水平不能用作非裔美国人胰岛素抵抗的标志物。