Fonseca V A, Reynolds T, Hemphill D, Randolph C, Wall J, Valiquet T R, Graveline J, Fink L M
Department of Medicine, University of Arkansas for Medical Sciences and John L. McClellan Memorial Veterans' Hospital, Little Rock 72205, USA.
J Diabetes Complications. 1998 Jul-Aug;12(4):181-6. doi: 10.1016/s1056-8727(97)00109-8.
The objective of this study was to determine if treatment of non-insulin-dependent diabetes mellitus (NIDDM) patients with the "insulin sensitizer" troglitazone, both as monotherapy and in combination with insulin, corrects the impaired fibrinolysis and activated coagulation associated with NIDDM. Patients participating in two clinical trials comparing troglitazone and placebo in patients with NIDDM were studied at the time of randomization and after 26 weeks of treatment. Eighteen patients were treated with troglitazone (ten in combination with insulin and eight as monotherapy) and eight were treated with placebo (four in each trial). Plasma concentrations of plasminogen activator inhibitor (PAI-1), prothrombin fragment F1+2, fibrinogen, and von Willebrand Factor (vWF) activity were measured. Plasma PAI-1 concentrations fell significantly from a mean of 68.8 +/- 32.3 ng/mL to 40.4 +/- 20.4 in the troglitazone treated group, but did not change significantly in the placebo treated group. Plasma PAI-1 concentrations were elevated in 15 patients treated with troglitazone and fell to normal in eight of them. There was no significant change in plasma F1+2, vWF, and fibrinogen, but plasma C-peptide and triglyceride concentrations fell significantly with troglitazone. This study demonstrates that troglitazone treatment is associated with a significant fall in plasma PAI-1 antigen concentrations in patients with NIDDM and, therefore, may have a beneficial effect on fibrinolysis.
本研究的目的是确定用“胰岛素增敏剂”曲格列酮治疗非胰岛素依赖型糖尿病（NIDDM）患者，无论是单一疗法还是与胰岛素联合使用，是否能纠正与NIDDM相关的纤维蛋白溶解受损和凝血激活。参与两项比较曲格列酮与安慰剂治疗NIDDM患者的临床试验的患者，在随机分组时和治疗26周后进行了研究。18例患者接受曲格列酮治疗（10例与胰岛素联合使用，8例单一疗法），8例接受安慰剂治疗（每项试验各4例）。测定了血浆纤溶酶原激活物抑制剂（PAI-1）、凝血酶原片段F1+2、纤维蛋白原和血管性血友病因子（vWF）活性的浓度。曲格列酮治疗组血浆PAI-1浓度从平均68.8±32.3 ng/mL显著降至40.4±20.4 ng/mL，而安慰剂治疗组无显著变化。15例接受曲格列酮治疗的患者血浆PAI-1浓度升高，其中8例降至正常。血浆F1+2、vWF和纤维蛋白原无显著变化，但曲格列酮治疗后血浆C肽和甘油三酯浓度显著下降。本研究表明，曲格列酮治疗与NIDDM患者血浆PAI-1抗原浓度显著下降有关，因此可能对纤维蛋白溶解有有益作用。
