Haffner Steven M
Department of Medicine, University of Texas Health Science Center at San Antonio, San Antonio, Texas 78229, USA.
Am J Cardiol. 2003 Aug 18;92(4A):18J-26J. doi: 10.1016/s0002-9149(03)00612-x.
Type 2 diabetes is associated with a marked increase in the incidence of coronary artery disease (CAD); however, the correlation between glycemia and CAD in patients with type 2 diabetes is only modestly positive. This relatively weak association between glycemia and CAD in subjects with diabetes may be caused by the existence of an atherogenic prediabetic state. In the San Antonio Heart Study, subjects who start with normal glucose tolerance and later develop type 2 diabetes have increased triglyceride levels, increased systolic blood pressure, and decreased levels of high-density lipoprotein cholesterol before the onset of type 2 diabetes. The basis for these atherogenic prediabetic changes may be related to insulin resistance rather than reduced insulin secretion. Recently, interest has focused on a possible role of fibrinolysis and increased subclinical inflammation, as determined by high-sensitivity C-reactive protein (CRP) levels. The Insulin Resistance Atherosclerosis Study found that insulin resistance, as determined by a frequently sampled glucose tolerance test, is significantly related to higher CRP levels, higher fibrinogen, and higher plasminogen activator inhibitor-1 (PAI-1) levels. The investigators also have shown that high PAI-1 and CRP levels are predictors of the development of type 2 diabetes. In addition, the Women's Health Study has shown that high CRP levels predict type 2 diabetes. Insulin-sensitizing interventions have been demonstrated to reduce these nontraditional risk factors. Rosiglitazone, an agent with insulin-sensitizing properties, decreases PAI-1 and CRP levels. Some of the adverse cardiovascular effects seen in patients with type 2 diabetes may be reversed by insulin-sensitizing agents.
2型糖尿病与冠状动脉疾病（CAD）的发病率显著增加相关；然而，2型糖尿病患者血糖与CAD之间的相关性仅为中度正相关。糖尿病患者中血糖与CAD之间这种相对较弱的关联可能是由动脉粥样硬化性糖尿病前期状态的存在所致。在圣安东尼奥心脏研究中，那些最初糖耐量正常后来发展为2型糖尿病的受试者，在2型糖尿病发病前甘油三酯水平升高、收缩压升高且高密度脂蛋白胆固醇水平降低。这些动脉粥样硬化性糖尿病前期变化的基础可能与胰岛素抵抗而非胰岛素分泌减少有关。最近，人们的兴趣集中在纤溶作用以及由高敏C反应蛋白（CRP）水平所确定的亚临床炎症增加的可能作用上。胰岛素抵抗动脉粥样硬化研究发现，通过频繁采样糖耐量试验所确定的胰岛素抵抗与更高的CRP水平、更高的纤维蛋白原以及更高的纤溶酶原激活物抑制剂-1（PAI-1）水平显著相关。研究人员还表明，高PAI-1和CRP水平是2型糖尿病发生的预测指标。此外，妇女健康研究表明，高CRP水平可预测2型糖尿病。胰岛素增敏干预已被证明可降低这些非传统危险因素。罗格列酮，一种具有胰岛素增敏特性的药物，可降低PAI-1和CRP水平。2型糖尿病患者中所见的一些不良心血管效应可能可通过胰岛素增敏剂得到逆转。
