Stitt Alan W, Jenkins Alicia J, Cooper Mark E
Dept of Ophthalmology, Royal Victoria Hospital, Queen's University of Belfast, Northern Ireland.
Expert Opin Investig Drugs. 2002 Sep;11(9):1205-23. doi: 10.1517/13543784.11.9.1205.
Diabetic complications are major cause of morbidity and mortality in patients with diabetes. While the precise pathogenic mechanism(s) underlying conditions such as diabetic retinopathy, diabetic nephropathy and increased risk of atherosclerosis remain ill-defined, it is clear that hyperglycaemia is a primary factor that initiates and promotes complications. Formation of advanced glycation end products (AGEs) correlate with glycaemic control, and these reactive adducts form on DNA, lipids and proteins where they represent pathophysiological modifications that precipitate dysfunction at a cellular and molecular level. Many of these adducts form rapidly during diabetes and promote progression of a raft of diabetes-related complications. Recent evidence also suggests an important interaction with other pathogenic mechanisms activated within the diabetic milieu. This review outlines the nature of AGE formation in biological systems and highlights accumulative evidence that implicates these adducts in diabetic complications. As more therapeutic agents are developed to inhibit AGE formation or limit their pathogenic influence during chronic diabetes, it is becoming clear that these anti-AGE strategies have an important role to play in the treatment of diabetic patients.
糖尿病并发症是糖尿病患者发病和死亡的主要原因。虽然糖尿病视网膜病变、糖尿病肾病以及动脉粥样硬化风险增加等疾病的确切致病机制仍不明确，但很明显高血糖是引发和促进并发症的主要因素。晚期糖基化终末产物（AGEs）的形成与血糖控制相关，这些反应性加合物在DNA、脂质和蛋白质上形成，它们代表了在细胞和分子水平上促使功能障碍的病理生理修饰。许多此类加合物在糖尿病期间迅速形成，并促进一系列糖尿病相关并发症的进展。最近的证据还表明，AGEs与糖尿病环境中激活的其他致病机制之间存在重要相互作用。本综述概述了生物系统中AGE形成的本质，并强调了表明这些加合物与糖尿病并发症有关的累积证据。随着越来越多的治疗药物被开发出来以抑制AGE形成或限制它们在慢性糖尿病期间的致病影响，很明显这些抗AGE策略在糖尿病患者的治疗中具有重要作用。
