Morishita Tetsuji, Uzui Hiroyasu, Ikeda Hiroyuki, Amaya Naoki, Kaseno Kenichi, Ishida Kentaro, Fukuoka Yoshitomo, Tada Hiroshi
Department of Cardiovascular Medicine, Faculty of Medical Sciences, University of Fukui, Japan.
Intern Med. 2019 Oct 1;58(19):2773-2781. doi: 10.2169/internalmedicine.2616-19. Epub 2019 Jun 27.
Objective Circulating endothelial progenitor cells (EPCs) are regulated by stromal cell-derived factor-1alpha (SDF-1α) and are reduced in type 2 diabetes mellitus (DM). SDF-1α is a substrate of dipeptidyl-peptidase-4 (DPP-4), so we investigated whether or not DPP-4-inhibitors modulate EPC levels in type 2 DM patients with coronary artery disease (CAD). Methods Thirty patients with CAD and type 2 DM treated using an ordinary regimen were enrolled. EPC and SDF-1α levels were compared between those receiving additional 24-week treatment with a DPP-4-inhibitor (n=11) and no additional treatment (n=19). We determined the HbA1c, 1.5-Anhydro-D-glucitol (1,5-AG), coronary flow reserve (CFR), brain natriuretic peptide (BNP), E/e', and circulating EPC proportion and SDF-1α levels at baseline and the end of follow-up. The CFR was assessed using a dual-sensor-equipped guidewire. The primary endpoints were changes in the EPC count, SDF-1α levels, and CFR from baseline to the end of follow-up. The secondary endpoints were changes in the HbA1c and 1,5-AG, which are useful clinical markers of postprandial hyperglycemia, as well as the BNP and E/e'. Results After the 6-month follow-up, compared with ordinary regimen subjects, the patients receiving a DPP-4-inhibitor showed no significant increase in the EPC proportion (-0.01±0.50 vs. 0.02±0.77%, p=0.87), SDF-1α level (-600.4±653.6 vs. -283.2±543.1 pg/mL, p=0.18), or CFR (0.0±0.2 vs. 0.1±0.6, p=0.20), whereas both the 1.5-AG level (2.4±4.6 vs. -0.7±2.5 μg/dL, p=0.07) and HbA1c (-0.8±1.8 vs. 0.0±0.7%, p=0.02) were improved. There were no significant differences between the two groups in changes in the BNP and E/e'. Conclusion DPP-4 inhibition with sitagliptin did not increase or decrease the EPC proportion, SDF-1α level, or CFR, although the glycemic control was improved.
目的 循环内皮祖细胞（EPCs）受基质细胞衍生因子-1α（SDF-1α）调控，且在2型糖尿病（DM）中数量减少。SDF-1α是二肽基肽酶-4（DPP-4）的底物，因此我们研究了DPP-4抑制剂是否能调节2型糖尿病合并冠心病（CAD）患者的EPC水平。方法 纳入30例采用常规方案治疗的CAD合并2型DM患者。比较接受DPP-4抑制剂额外治疗24周的患者（n = 11）和未接受额外治疗的患者（n = 19）的EPC和SDF-1α水平。我们测定了基线及随访结束时的糖化血红蛋白（HbA1c）、1,5-脱水-D-葡萄糖醇（1,5-AG）、冠状动脉血流储备（CFR）、脑钠肽（BNP）、E/e'以及循环EPC比例和SDF-1α水平。使用配备双传感器的导丝评估CFR。主要终点为从基线到随访结束时EPC计数、SDF-1α水平和CFR的变化。次要终点为HbA1c和1,5-AG的变化，这是餐后高血糖的有用临床标志物，以及BNP和E/e'的变化。结果 6个月随访后，与常规方案治疗的患者相比，接受DPP-4抑制剂治疗的患者的EPC比例（-0.01±0.50 vs. 0.02±0.77%，p = 0.87）、SDF-1α水平（-600.4±653.6 vs. -283.2±543.1 pg/mL，p = 0.18）或CFR（0.0±0.2 vs. 0.1±0.6，p = 0.20）均无显著增加，而1,5-AG水平（2.4±4.6 vs. -0.7±2.5 μg/dL，p = 0.07）和HbA1c（-0.8±1.8 vs. 0.0±0.7%，p = 0.02）均有所改善。两组在BNP和E/e'的变化方面无显著差异。结论 尽管血糖控制得到改善，但使用西他列汀抑制DPP-4并未增加或降低EPC比例、SDF-1α水平或CFR。
