基于glp-1的2型糖尿病治疗.pptVIP

Slide No. * ? ? 利拉鲁肽总体治疗满意度优于西格列汀 p=0.0300 p=0.3962 Pratley et al. Lancet 2010,375:1447-56 3.51 4.35 2.96 0 1 2 3 4 5 6 利拉鲁肽 1.2 mg (n=164) 利拉鲁肽 1.8 mg (n=171) 西格列汀 100 mg (n=170) 总体治疗满意度评分变化 Thank you * * 在了解肠促胰素之前先看一个研究 在上世纪80年代，Nauck等开展了一项试验，8名健康受试者经过一夜空腹后分别通过静脉和口服两种途径给予等量的葡萄糖。当受试者血糖浓度相同时，发现通过口服给予的葡萄糖与静脉给予葡萄糖相比刺激了更多的胰岛素的释放，这种现象称为肠促胰岛效应。右侧图中所示的两条曲线下面积的差值即为肠促胰素效应，科学家推测口服给糖与静脉给糖相比，可能通过肠道吸收时触发了某种物质的释放，这种物质进而刺激了胰岛素的释放。 * * 在糖尿病患者中，肠促胰素的效应与健康人群有所不同。左图是正常人口服葡萄糖或静脉推注葡萄糖得到的胰岛素反应。这右图所示的2型糖尿病患者中的情况有明显不同。我们都很清楚，如果我们口服葡萄糖之后，糖尿病患者得到的早相远远低于正常人，而后相有一个高代偿。在静脉推注葡萄糖时患者与正常人的胰岛素分泌情况也不一样。 那么，糖尿病患者中的GLP-1和GIP分泌情况是怎样的呢？ Reduced incretin effect in type 2 (non-insulin-dependent) diabetes. Integrated incremental immunoreactive insulin and connecting peptide responses to an oral glucose load of 50 g and an isoglycaemic intravenous glucose infusion, respectively, were measured in 14 Type 2 (non-insulin-dependent) diabetic patients and 8 age- and weight-matched metabolically healthy control subjects. Differences between responses to oral and intravenous glucose administration are attributed to factors other than glucose itself (incretin effect). Despite higher glucose increases, immunoreactive insulin and connecting peptide responses after oral glucose were delayed in diabetic patients. Integrated responses were not significantly different between both groups. However, during isoglycaemic intravenous infusion, insulin and connecting peptide responses were greater in diabetic patients than in control subjects as a consequence of the higher glycaemic stimulus. The contribution of incretin factors to total insulin responses was 72.8 +/- 6.9% (100% = response to oral load) in control subjects and 36.0 +/- 8.8% in diabetic patients (p less than or equal to 0.05). The contribution to connecting peptide responses was 58.4 +/- 7.6% in control subjects and 7.6 +/- 14.5% (p less than or equal to 0.05) in diabetic patients. Ratios of integrated insulin to connecting peptide responses sugge