Hsueh W A, Law R E
Department of Medicine, University of California/Los Angeles, School of Medicine, USA.
Am J Med. 1998 Jul 6;105(1A):4S-14S. doi: 10.1016/s0002-9343(98)00205-8.
Although low-density lipoprotein (LDL) cholesterol is a critically important factor in the development of atherosclerosis, nearly half the patients with coronary artery disease have LDL cholesterol levels within the National Cholesterol Education Program (NCEP) guidelines. Therefore, attention has focused on other modifiable risk factors that could strongly impact the development of coronary artery disease. Type 2 diabetics have a 3-fold increased risk of coronary artery disease; prediabetics, without chronic hyperglycemia, have a 2-fold increased risk compared with normal subjects. Insulin resistance has also been implicated as the cause of atherosclerosis. Insulin resistance is associated with hyperinsulinemia and a constellation of other factors, some of which are themselves independent risk factors for coronary artery disease. These include reduced levels of high-density lipoprotein (HDL) cholesterol, hypertriglyceridemia, increased small dense LDL particles, hypertension, visceral obesity, and increased levels of plasminogen activator inhibitor-1 (PAI-1). Hyperinsulinemia and insulin resistance at the vascular level also may contribute to vascular injury and the atherosclerotic process. Current studies suggest that controlling hyperglycemia, LDL cholesterol, and blood pressure are important to protect the diabetic from atherosclerosis. A key question, particularly in type 2 diabetes, is to define the best regimen for glucose control that will protect the vasculature. Sulfonylureas, metformin, and troglitazone have direct vascular actions. Metformin lowers LDL cholesterol and triglycerides, while troglitazone reverses many of the components associated with the insulin resistance syndrome. Clinical trials focusing on coronary artery disease outcomes are now warranted to prevent coronary artery disease, the major vascular complication and cause of mortality in diabetes.
尽管低密度脂蛋白（LDL）胆固醇是动脉粥样硬化发展的一个极其重要的因素，但近一半的冠心病患者的LDL胆固醇水平在国家胆固醇教育计划（NCEP）指南范围内。因此，注意力已集中在其他可改变的危险因素上，这些因素可能对冠心病的发展产生重大影响。2型糖尿病患者患冠心病的风险增加3倍；糖耐量异常患者，无慢性高血糖，与正常受试者相比，患冠心病的风险增加2倍。胰岛素抵抗也被认为是动脉粥样硬化的病因。胰岛素抵抗与高胰岛素血症及一系列其他因素有关，其中一些因素本身就是冠心病的独立危险因素。这些因素包括高密度脂蛋白（HDL）胆固醇水平降低、高甘油三酯血症、小而密的LDL颗粒增加、高血压、内脏肥胖以及纤溶酶原激活物抑制剂-1（PAI-1）水平升高。血管水平的高胰岛素血症和胰岛素抵抗也可能导致血管损伤和动脉粥样硬化进程。目前的研究表明，控制高血糖、LDL胆固醇和血压对于保护糖尿病患者免受动脉粥样硬化的影响很重要。一个关键问题，特别是在2型糖尿病中，是确定能保护血管系统的最佳血糖控制方案。磺脲类、二甲双胍和曲格列酮具有直接的血管作用。二甲双胍可降低LDL胆固醇和甘油三酯，而曲格列酮可逆转许多与胰岛素抵抗综合征相关的成分。现在有必要进行关注冠心病结局的临床试验，以预防冠心病，这是糖尿病主要的血管并发症和死亡原因。
