Strain W David, Smith Christine
Diabetes and Vascular Medicine, University of Exeter Medical School, Exeter, UK.
Novo Nordisk UK Ltd, London, UK.
Diabetes Ther. 2016 Jun;7(2):175-85. doi: 10.1007/s13300-016-0165-z. Epub 2016 Mar 24.
Poorly controlled diabetes is characterized by premature cardiovascular mortality and morbidity. The mechanisms linking hyperglycemia with accelerated atherosclerotic disease have not been fully elucidated; however, are thought to be mediated through vascular inflammation, oxidative stress and endothelial dysfunction. The advent of incretin-based therapy, whether by increasing endogenous glucagon-like peptide (GLP)-1 and glucose-dependent inhibitory polypeptide by inhibition of their breakdown using di-peptidyl peptidase 4 inhibitors, or augmenting GLP-1 activity using either exendin-4-based drugs or synthetic GLP-1 analogs promised not just improvements in glycemic control, but improvements in endothelial function, lipid profiles and markers of vascular inflammation. As such, it was anticipated they would demonstrate cardiovascular benefit in those with diabetes, indeed early meta-analyses suggested cardiovascular events would be reduced. To date, however, this benefit has failed to materialize, indeed the cardiovascular outcome trials, whilst meeting their primary endpoint of cardiovascular safety, have failed to demonstrate any improvements in stroke or myocardial infarction. This review will explore the data and attempt to answer the question: what went wrong?
糖尿病控制不佳的特征是心血管疾病过早出现死亡和发病。高血糖与加速动脉粥样硬化疾病之间的联系机制尚未完全阐明；然而，人们认为其是通过血管炎症、氧化应激和内皮功能障碍介导的。基于肠促胰岛素的治疗方法出现了，无论是使用二肽基肽酶4抑制剂抑制内源性胰高血糖素样肽（GLP）-1和葡萄糖依赖性促胰岛素多肽的分解来增加它们，还是使用基于艾塞那肽-4的药物或合成GLP-1类似物来增强GLP-1活性，都不仅有望改善血糖控制，还能改善内皮功能、血脂谱和血管炎症标志物。因此，人们预计它们会对糖尿病患者显示出心血管益处，确实早期的荟萃分析表明心血管事件将会减少。然而，迄今为止，这种益处并未实现，实际上心血管结局试验虽然达到了心血管安全性的主要终点，但未能证明在中风或心肌梗死方面有任何改善。本综述将探讨相关数据并试图回答这个问题：哪里出了问题？
