Division of Diabetes, Metabolism, and Endocrinology, Department of Medicine, Showa University School of Medicine.
Circ J. 2019 Aug 23;83(9):1822-1828. doi: 10.1253/circj.CJ-19-0618. Epub 2019 Jul 30.
Despite the early loss of glycemic differences between the original intensive therapy group and conventional treatment in the DCCT/EDIC and UKPDS 80 trials, a continued reduction in microvascular risk and risk reductions for emergency myocardial infarction and all-cause death were observed 10-30 years after the end of these trials. These observations demonstrated that so-called "metabolic memory" could cause chronic abnormalities in diabetic vessels that are not easily reversed, even by subsequent improvement in blood glucose levels, thus suggesting a long-term beneficial influence of early metabolic control; that is, legacy effects on the risk of vascular complications and death in patients with both type 1 and type 2 diabetes. Formation and accumulation of advanced glycation endproducts (AGEs) are known to progress at an accelerated rate under diabetes. Furthermore, AGEs are hardly degraded and remain for a long time in diabetic vessels even after glycemic control is improved. Therefore, AGEs could explain why former cumulative diabetic exposure could contribute to current progression of vascular complications in diabetes. Here, the clinical utility of measurement of serum and tissue accumulation levels of AGEs for evaluating the prevalence and severity of numerous types of cardiovascular disease is reviewed and novel therapeutic strategies that could target the AGE-RAGE axis in CVD are discussed.
尽管在 DCCT/EDIC 和 UKPDS 80 试验中，最初强化治疗组与常规治疗组之间的血糖差异在早期就已经消失，但在这些试验结束后 10-30 年，仍观察到微血管风险持续降低，以及紧急心肌梗死和全因死亡风险降低。这些观察结果表明，所谓的“代谢记忆”可能导致糖尿病血管的慢性异常，即使随后血糖水平得到改善，也不容易逆转，这表明早期代谢控制具有长期有益影响；也就是说，对 1 型和 2 型糖尿病患者血管并发症和死亡风险的长期影响。已知在糖尿病患者中，糖基化终产物 (AGE) 的形成和积累会加速。此外，即使血糖控制得到改善，AGE 在糖尿病血管中也很难降解并长时间存在。因此，AGE 可以解释为什么以前的累积糖尿病暴露可能导致糖尿病血管并发症的当前进展。在这里，我们回顾了测量血清和组织 AGE 积累水平在评估多种心血管疾病的患病率和严重程度方面的临床应用，并讨论了针对 CVD 中 AGE-RAGE 轴的新型治疗策略。
