Fibroblast Growth Factor-23 and Klotho in Heart Failure and Type 2 Diabetes Mellitus

最近，美国监管机构食品和药物管理局（FDA）增加了关于含有二肽基肽酶-4抑制剂沙格列汀和阿格列汀的新型2型糖尿病药物的心力衰竭警告。尿磷酸化激素成纤维细胞生长因子-23（FGF-23）及其共受体klotho作为一种新的有前途的生物标志物出现在心血管死亡率和发病率的统计中。因此，心力衰竭进展的生物标志物指示可能是有用的，以指导gliptins治疗。我在此申请在TIMI研究组的研究奖学金，以促进我作为一个临床科学家的培训。 第一个项目将是一个额外的分析，以阐明FGF-23和klotho在心血管死亡率和发病率方面的作用。在5380例2型糖尿病和近期急性冠状动脉综合征患者中进行了阿罗格列酮与安慰剂在主要心血管事件方面的非劣效性研究。此外，我们的目标是确定心脏失代偿风险最高的患者和特别受益于阿格列汀治疗的患者。

Recently, the US-regulatory authority the Food and Drug Administration (FDA) added a heart failure warning regarding novel type 2-diabetes drugs that contain the dipeptidyl peptidase-4 inhibitors saxagliptin and alogliptin. The phosphaturic hormone Fibroblast Growth Factor-23 (FGF-23) and its co-receptor klotho emerged as a novel promising biomarker in prognostication of cardiovascular mortality and morbidity. Thus, biomarker indicative of heart failure progression may be useful to guide therapy with gliptins.I hereby apply for a research fellowship at the TIMI study group to promote my training as a clinical scientist. The first project will be an additional analysis of the EXAMINE trial to elucidate the role of FGF-23 and klotho in regard to cardiovascular mortality and morbidity. The EXAMINE trial was conducted as a non-inferiority study comparing alogliptin with placebo with respect to major cardiovascular events in 5380 patients with type 2 diabetes and recent acute coronary syndromes. In addition, we aim to identify both patients at highest risk for cardiac decompensation and patients who benefit particularly from therapy with alogliptin.