METABOLIC RESPONSES TO VARIATION IN DIETARY COMPOSITION

动脉粥样硬化性冠状动脉疾病是人类的主要健康问题之一。与低密度脂蛋白胆固醇(LDL-C)、中密度脂蛋白胆固醇(HDL-C)水平呈正相关。最近的研究集中在胰岛素抵抗在冠心病的形成中所起的作用。已有研究表明，在患有混合性高脂血症(胆固醇和甘油三酯增加)的个体中，膳食胆固醇提高血浆胆固醇浓度的能力比具有其他脂类表型的个体更大。患有混合性高脂血症的人通常会出现一系列异常，这会增加患冠心病的风险。这些异常包括空腹甘油三酯升高和高密度脂蛋白浓度降低、餐后血脂升高、低密度脂蛋白颗粒变小和密度增大、高尿酸血症、高血压和高胰岛素血症。根据我们的实验室观察，患有混合型高脂血症的受试者对饮食胆固醇的反应更强，合并高脂血症的受试者很有可能对饮食胆固醇表现出更大的反应，胰岛素抵抗的受试者(或其子集)很有可能代表了对饮食胆固醇反应过度的人群的很大一部分。如果胰岛素抵抗的个体最容易受到饮食中胆固醇增加的影响，那么限制胆固醇的努力显然应该针对这一群体。相反，如果胰岛素敏感者对饮食中胆固醇的增加表现出很小的反应，那么就没有理由限制这类人的胆固醇摄入量。在这种情况下，了解饮食反应差异的原因并确定饮食胆固醇反应者的特征将有助于采取更有针对性的方法，将重点放在那些将从饮食胆固醇限制中获得最大降胆固醇好处的患者身上。这反过来将导致对美国人饮食的理性建议，作为一个整体。

Atherosclerotic coronary artery disease (CAD) is one of the major health problems in the human population. It is positively associated with levels of low density lipoprotein cholesterol (LDL-C), intermediate density lipoprotein cholesterol (HDL-C). Recently research has focused on the role that insulin resistance plays in the establishment of coronary heart disease. It has been shown that the ability of dietary cholesterol to raise plasma cholesterol concentration in individuals with combined hyperlipidemia (increased cholesterol and triglycerides) is greater than those who have other lipid phenotypes. Individuals with combined hyperlipidemia often present with a cluster of abnormalities, which increase the risk of coronary heart disease. These abnormalities consist of higher fasting triglyceride and lower high density (HDL) lipoprotein concentrations, an enhanced degree of postprandial lipemia, smaller and denser low density lipoprotein (LDL particles, hyperuricemia, hypertension and hyperinsulinemia. Based upon our laboratory observations that subjects with combined hyperlipidemia show a greater response to dietary cholesterol, there is an excellent chance that subjects with combined hyperlipidemia show a greater response to dietary cholesterol, there is an excellent chance that subjects with insulin resistance (or a subset thereof) represent a significant fraction of the population that have an exaggerated response to dietary cholesterol. If insulin resistant individuals are most susceptible to an increase in dietary cholesterol, it seems obvious that efforts to limit cholesterol should be aimed at this group. Conversely, if insulin sensitive individuals demonstrate very little response to increases in dietary cholesterol, there is little justification for limiting cholesterol intake in such persons. In this light, understanding the causes of variations in dietary response and identifying the characteristics of dietary cholesterol responders will facilitate a more targeted approach focusing on patients who would gain the greatest plasma cholesterol lowering benefit from dietary cholesterol restrictions. This in turn will lead to rational recommendations for the American diet to the public as a whole.