METABOLIC RESPONSES TO VARIATION IN DIETARY COMPOSITION

动脉粥样硬化性冠状动脉疾病（CAD）是人类主要的健康问题之一。 它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发病中的作用。 研究表明，饮食胆固醇提高混合型高脂血症（胆固醇和甘油三酯增加）患者血浆胆固醇浓度的能力大于具有其他脂质表型的患者。 混合型高脂血症患者常出现一系列异常，这增加了冠心病的风险。 这些异常包括较高的空腹甘油三酯和较低的高密度脂蛋白（HDL）浓度，增强的餐后脂血症程度，更小和更密集的低密度脂蛋白（LDL 颗粒、高尿酸血症、高血压和高胰岛素血症。 基于我们的实验室观察，患有混合型高脂血症的受试者对膳食胆固醇显示出更大的响应，患有混合型高脂血症的受试者很有可能对膳食胆固醇显示出更大的响应，患有胰岛素抵抗的受试者（或其子集）很有可能代表对膳食胆固醇具有夸大响应的人群的显著部分。如果胰岛素抵抗个体最容易受到饮食胆固醇增加的影响，那么很明显，限制胆固醇的努力应该针对这一群体。 相反，如果胰岛素敏感个体对膳食胆固醇的增加表现出非常小的反应，则没有理由限制这些人的胆固醇摄入量。 在这种情况下，了解饮食反应变化的原因并确定饮食胆固醇反应者的特征将有助于更有针对性的方法，重点关注从饮食胆固醇限制中获得最大血浆胆固醇降低益处的患者。 这反过来又会导致对美国饮食的理性建议，以公众作为一个整体。

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.