Heart Disease Risk Factors In African Americans

非裔美国人的心脏病危险因素

• 批准号: 7337554
• 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/7337554
• 关键词: Heart; Disease; Risk; Factors; African

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是胰岛素耐药性作为葡萄糖调节激素。非洲裔美国人，特别是非裔美国人妇女，在这些情况下遭受不成比例的痛苦。我们认为，非洲裔美国妇女可能对胰岛素抑制脂解的能力提高了敏感性，这有助于她们加速肥胖和相关并发症的发展。这项研究的假设是，非洲裔美国男性对胰岛素具有抗糖调节激素的抵抗力，并且抗胰岛素作为脂肪调节激素具有抵抗力。相比之下，非洲裔美国妇女对胰岛素具有抗糖调节激素的抵抗力，但对胰岛素作为脂肪调节激素敏感。经常采样的静脉葡萄糖耐量测试用于测量胰岛素的作用，作为葡萄糖调节激素。不幸的是，没有胰岛素作用指数作为脂肪调节激素。因此，我们正在通过在经常采样的葡萄糖耐受性测试中获得游离脂肪酸来开发该指数。我们的目标是能够进行一项测试，以获取有关两种胰岛素作用的信息。然而，在经常采样的静脉葡萄糖耐受性测试期间，游离脂肪酸敏感性的指数的发展涉及复杂的数学建模，需要进行验证。当我们努力开发该指数时，我们研究了甘油三酸酯（TG）水平的性别差异以及非裔美国人的体内脂肪含量和分布。我们发现，非裔美国人的TG水平低于高加索人所报告的水平。非裔美国女性的进一步TG水平低于男性。这种性别差异的原因之一可能是体内脂肪分布中的性别差异。我们确定了从iLiac Crest到隔膜圆顶的连续切片计算机断层扫描，非洲裔美国妇女的内脏脂肪量低于男性。由于内脏脂肪是用于合成TG的游离脂肪酸的主要来源，因此这可能是TG水平上性别差异的原因之一。我们还发现，在存在胰岛素抵抗的情况下，脂蛋白脂肪酶（LPL）的活性不会受到损害。因此，即使在存在胰岛素抵抗的情况下，非裔美国人也能够有效地从循环中清除TG。尽管LPL活性水平或胰岛素抵抗的作用均无性差异，但胰岛素抵抗损害LPL活性的能力可能有助于为什么非裔美国人的TG水平低于高加索人。这是因为在高加索人中，胰岛素抵抗会导致LPL活性和更高TG水平的明显损害。此外，缺乏对LPL活动的影响可能解释了我们的其他发现，与高加索人不同，TG水平不能用于非洲裔美国人的胰岛素抵抗标志。