Heart Disease Risk Factors In African Americans

肥胖、糖尿病和心脏病的特点是对胰岛素（一种血糖调节激素）的抵抗。非裔美国人，尤其是非裔美国妇女，在这些情况下遭受了不成比例的痛苦。我们认为非裔美国女性可能对胰岛素更敏感。抑制脂肪分解的能力，这有助于他们加速肥胖和相关并发症的发展。本研究的假设是，非洲裔美国男性对作为血糖调节激素的胰岛素和作为脂肪调节激素的胰岛素有抵抗性。相比之下，非洲裔美国女性对作为血糖调节激素的胰岛素有抵抗性，但对作为脂肪调节激素的胰岛素敏感。频繁取样的静脉葡萄糖耐量试验用于测量胰岛素？作为血糖调节激素的作用。不幸的是没有胰岛素指数？S作为脂肪调节激素的作用。因此，我们正致力于通过在频繁取样的葡萄糖耐量试验中获得游离脂肪酸来开发这一指标。我们的目标是能够通过一次测试获得胰岛素两种作用的信息。然而，在频繁采样的静脉葡萄糖耐量试验中，游离脂肪酸对胰岛素敏感性指数的发展涉及复杂的数学模型，需要验证。在我们努力开发这个指数的过程中，我们研究了非洲裔美国人甘油三酯（TG）水平以及体脂含量和分布的性别差异。我们发现非洲裔美国人的TG水平比报道的白种人要低。非裔美国女性的进一步TG水平低于男性。造成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。我们使用从髂骨到横膈膜圆顶的连续切片计算机断层扫描确定非裔美国女性的内脏脂肪体积比男性低。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水平存在性别差异的原因之一。我们还发现，脂蛋白脂肪酶（LPL）的活性，负责从循环中清除TG的酶，在胰岛素抵抗的存在下不会受损。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活性可能是非洲裔美国人TG水平低于白种人的原因。这是因为在白种人中，胰岛素抵抗导致LPL活性明显受损和TG水平升高。此外，缺乏对LPL活性的影响可以解释我们的其他发现，即与高加索人不同，TG水平不能用于非洲裔美国人的胰岛素抵抗标记。

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.