Veiraiah Arvindan
Llandough Hospital, Penarth, Wales, UK.
Angiology. 2005 Jul-Aug;56(4):431-8. doi: 10.1177/000331970505600411.
Hyperlipidemia and its treatment are currently recognized as important modulators of cardio-vascular mortality in the presence of disordered glucose control. On the other hand, the effects of hyperglycemia and its treatment on hyperlipidemia are not widely appreciated. Hyperglycemia is commonly associated with an increase in intestinal lipoproteins and a reduction in high-density lipoprotein (HDL). This could be a consequence of hyperglycemia-induced glycation of lipoproteins, which reduces the uptake and catabolism of the lipoproteins via the classical low-density lipoprotein (LDL) receptor. A high dietary carbohydrate load increases the glycation of intestinal lipoproteins, prolongs their circulation, and increases their plasma concentration. Hyperglycemia also leads to inhibition of lipoprotein lipase, further aggravating hyperlipidemia. Circulating advanced glycation end-products (AGEs) also bind lipoproteins and delay their clearance, a mechanism that has particularly been implicated in the dyslipidemia of diabetic nephropathy. As uptake via scavenger receptors is not inhibited, glycation increases the proportion of lipoproteins that are taken up via inflammatory cells and decreases the proportion taken up by hepatocytes via classical LDL receptors. This promotes the formation of atheromatous plaques and stimulates inflammation. Hyperglycemia increases the formation of oxidized LDL and glycated LDL, which are important modulators of atherosclerosis and cardiovascular death. The risk of cardiovascular death is increased by even short-term derangement of blood sugar control, owing perhaps to the glycation of lipoproteins and other critical proteins. Glycated LDL could prove very useful in measuring the effect of hyperglycemia on cardiovascular disease, its risk factors, and its complications. Comparing different glucose-lowering and lipid-lowering drugs in respect to their influence on glycated LDL could increase knowledge of the mechanism by which they alter cardiovascular risk.
在血糖控制紊乱的情况下，高脂血症及其治疗目前被认为是心血管死亡率的重要调节因素。另一方面，高血糖及其治疗对高脂血症的影响尚未得到广泛认识。高血糖通常与肠道脂蛋白增加和高密度脂蛋白（HDL）减少有关。这可能是高血糖诱导脂蛋白糖基化的结果，它通过经典的低密度脂蛋白（LDL）受体减少脂蛋白的摄取和分解代谢。高碳水化合物饮食负荷会增加肠道脂蛋白的糖基化，延长其循环时间，并增加其血浆浓度。高血糖还会导致脂蛋白脂肪酶的抑制，进一步加重高脂血症。循环中的晚期糖基化终产物（AGEs）也会结合脂蛋白并延迟其清除，这一机制尤其与糖尿病肾病的血脂异常有关。由于通过清道夫受体的摄取未受抑制，糖基化增加了通过炎症细胞摄取的脂蛋白比例，并减少了肝细胞通过经典LDL受体摄取的比例。这促进了动脉粥样斑块的形成并刺激炎症。高血糖会增加氧化LDL和糖化LDL的形成，它们是动脉粥样硬化和心血管死亡的重要调节因素。即使血糖控制出现短期紊乱，心血管死亡风险也会增加，这可能是由于脂蛋白和其他关键蛋白质的糖基化所致。糖化LDL可能在衡量高血糖对心血管疾病、其危险因素及其并发症的影响方面非常有用。比较不同降糖和降脂药物对糖化LDL的影响，可以增加对它们改变心血管风险机制的认识。
