Asvold B O, Jonsbu M, Grill V
Medisinsk avdeling, Regionsykehuset i Trondheim.
Tidsskr Nor Laegeforen. 2000 Sep 10;120(21):2560-4.
The use of sulphonylureas for type 2 diabetes has been debated since 1970, when the University Group Diabetes Program (UGDP) reported increased cardiovascular mortality with tolbutamide treatment.
We try to present a balanced review of the current knowledge of the possible cardiovascular side effects of sulphonylureas.
Recent studies on the molecular actions of sulphonylureas show that sulphonylureas, in addition to closing K+ ATP channels in insulin producing cells, also do so in the myocard and in vascular smooth muscle. This action could theoretically have adverse effects during ischaemia. Experimental studies show effects on cardiac parameters and also differences in such effects between sulphonylureas, but leave the net effect of sulphonylureas during ischaemia uncertain. The United Kingdom Prospective Diabetes Study (UKPDS), published in September 1998, found no increase in cardiovascular mortality with the use of sulphonylureas. One possible explanation for the difference in relation to the UGDP is the exclusion of cardiovascular patients in the UKPDS.
Our interpretation is that sulphonylureas are without clinically important cardiovascular side effects in type 2 diabetic patients without cardiovascular disease. Clinical studies focusing on the effects of sulphonylurea in cardiovascular patients are, however, lacking. More studies are also needed on the effect of newly developed and possibly more selective sulphonylureas as well as related compounds.
自1970年大学组糖尿病项目(UGDP)报告甲苯磺丁脲治疗会增加心血管死亡率以来,磺脲类药物用于2型糖尿病的治疗一直存在争议。
我们试图对磺脲类药物可能的心血管副作用的现有知识进行全面综述。
近期关于磺脲类药物分子作用的研究表明,磺脲类药物除了能关闭胰岛素分泌细胞中的K+ATP通道外,还能作用于心肌和血管平滑肌中的该通道。从理论上讲,这种作用在缺血期间可能产生不利影响。实验研究显示了对心脏参数的影响以及不同磺脲类药物之间这种影响的差异,但磺脲类药物在缺血期间的总体影响仍不明确。1998年9月发表的英国前瞻性糖尿病研究(UKPDS)发现,使用磺脲类药物不会增加心血管死亡率。与UGDP研究结果存在差异的一个可能解释是,UKPDS排除了心血管疾病患者。
我们的解读是,磺脲类药物对无心血管疾病的2型糖尿病患者没有临床上重要的心血管副作用。然而,目前缺乏针对心血管疾病患者的磺脲类药物疗效的临床研究。对于新开发的、可能更具选择性的磺脲类药物以及相关化合物的作用,也需要进行更多研究。