Effect of postprandial hypertriglyceridemia and hyperglycemia on circulating adhesion molecules and oxidative stress generation and the possible role of simvastatin treatment
Effect of postprandial hypertriglyceridemia and hyperglycemia on circulating adhesion molecules and oxidative stress generation and the possible role of simvastatin treatment
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DOI：
10.2337/diabetes.53.3.701
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发表时间：
2004-03-01
期刊：
影响因子：
7.7
通讯作者：
Giugliano, D
中科院分区：
文献类型：
--
作者：
Ceriello, A;Quagliaro, L;Giugliano, D
粘附分子，特别是细胞内粘附分子（ICAM）-1，血管细胞粘附分子（VCAM）-1和E-选择素，与心血管疾病有关。据报道，糖尿病患者中这些分子的水平升高。餐后高血糖症和高血糖症被认为是心血管疾病的危险因素，有证据表明，餐后高血糖症和高血糖症可能诱导循环粘附分子增加。然而，这两个因素的不同作用是一个有争议的问题。30名2型糖尿病患者和20名正常受试者吃了三种不同的食物：高脂肪餐，75克葡萄糖单独，高脂肪餐加葡萄糖。在试验期间测定血糖、甘油三酯、血浆硝基酪氨酸、ICAM-1、VCAM-1和E-选择素。随后，糖尿病患者服用辛伐他汀40 mg/天或安慰剂12周。在基线、研究开始后3 - 6天和每次研究结束时再次进行这三项测试。在正常和糖尿病受试者中，高脂肪负荷和葡萄糖单独产生硝基酪氨酸、ICAM-1、VCAM-1和E-选择素血浆水平的增加。当高脂肪和葡萄糖结合时，这些影响更加明显。短期辛伐他汀治疗对血脂参数没有影响，但降低了对粘附分子和硝基酪氨酸的影响，这在每个不同的测试中都可以观察到。长期辛伐他汀治疗伴随着餐后甘油三酯的较低增加，随后是ICAM-1，VCAM-1，E-选择素和硝基酪氨酸在测试过程中的较小变化。这项研究显示，餐后高血糖和高血糖对ICAM-1，VCAM-1和E-选择素血浆水平的独立和累积效应，表明氧化应激是这种效应的共同介质。辛伐他汀显示出对氧化应激和粘附分子的血浆水平的有益作用，这可能归因于除了药物的降脂作用之外的直接作用。
Adhesion molecules, particularly intracellular adhesion molecule (ICAM)-1, vascular cell adhesion molecule (VCAM)-1, and E-selectin, have been associated with cardiovascular disease. Elevated levels of these molecules have been reported in diabetic patients. Postprandial hypertriglyceridemia and hyperglycemia are considered risk factors for cardiovascular disease, and evidence suggests that postprandial hypertriglyceridemia and hyperglycemia may induce an increase in circulating adhesion molecules. However, the distinct role of these two factors is a matter of debate. Thirty type 2 diabetic patients and 20 normal subjects ate three different meals: a high-fat meal, 75 g of glucose alone, and a high-fat meal plus glucose. Glycemia, triglyceridemia, plasma nitrotyrosine, ICAM-1, VCAM-1, and E-selectin were assayed during the tests. Subsequently, diabetic subjects took simvastatin 40 mg/day or placebo for 12 weeks. The three tests were performed again at baseline, between 3 and 6 days after starting the study, and at the end of each study. High-fat load and glucose alone produced an increase of nitrotyrosine, ICAM-1, VCAM-1, and E-selectin plasma levels in normal and diabetic subjects. These effects were more pronounced when high fat and glucose were combined. Short-term simvastatin treatment had no effect on lipid parameters, but reduced the effect on adhesion molecules and nitrotyrosine, which was observed during every different test. Long-term simvastatin treatment was accompanied by a lower increase in postprandial triglycerides, which was followed by smaller variations in ICAM-1, VCAM-1, E-selectin, and nitrotyrosine during the tests. This study shows an independent and cumulative effect of postprandial hypertriglyceridemia and hyperglycemia on ICAM-1, VCAM-1, and E-selectin plasma levels, suggesting oxidative stress as a common mediator of such effects. Simvastatin shows a beneficial effect on oxidative stress and the plasma levels of adhesion molecules, which may be ascribed to a direct effect in addition to the lipid-lowering action of the drug.