Department of Endocrinology and Metabolism, Dokkyo Medical University, Tochigi 321-0293, Japan.
Department of Endocrinology and Metabolism, Dokkyo Medical University, Tochigi 321-0293, Japan.
J Diabetes Complications. 2020 Nov;34(11):107703. doi: 10.1016/j.jdiacomp.2020.107703. Epub 2020 Jul 31.
Elevation of the plasma concentration of plasminogen activator inhibitor-1 (PAI-1), a rapid-acting inhibitor of fibrinolysis, is associated with development of vascular thrombotic diseases, including coronary artery disease and stroke. We investigated the effects of empagliflozin, a sodium-glucose co-transporter-2 (SGLT2) inhibitor, on the plasma concentration of PAI-1 and fibrinolytic activity in patients with type 2 diabetes.
In a randomized, active-controlled, open-label trial, 51 patients with type 2 diabetes were randomly allocated at a 2:1 ratio to receive empagliflozin (10 mg/day, n = 31) or standard therapy (n = 18) for 12 weeks. We measured the plasma concentrations of PAI-1 and plasmin-α2-antiplasmin complex (PAP) as indicators of fibrinolytic activity. Serum leptin and high-molecular weight (HMW) adiponectin were also measured.
In 49 patients who completed the trial, baseline plasma PAI-1 showed a positive correlation with body weight, visceral fat area (VFA), γ-glutamyltranspeptidase (GGT), leptin, and the platelet count, while it showed a negative correlation with HDL cholesterol and PAP. Body weight and VFA decreased significantly in the empagliflozin group, but not in the control group. The serum level of GGT showed a significant decrease at 12 weeks in the empagliflozin group, while it was unchanged in the control group. Serum HMW adiponectin increased significantly in the empagliflozin group. Plasma PAI-1 decreased significantly by 25% in the empagliflozin group, but not in the control group. In the empagliflozin group, the change of plasma PAI-1 was positively correlated with the changes of body weight and leptin, but was negatively correlated with the change of PAP.
Empagliflozin reduced the plasma PAI-1 concentration through its synergistic actions of a glucose-lowering effect, VFA loss, and restoring the adipokine balance. (Clinical trial registry: UMIN000025418).
纤溶酶原激活物抑制剂-1（PAI-1）血浆浓度升高是血管血栓性疾病（包括冠状动脉疾病和中风）发展的一个标志。我们研究了钠-葡萄糖协同转运蛋白-2（SGLT2）抑制剂恩格列净对 2 型糖尿病患者 PAI-1 血浆浓度和纤溶活性的影响。
在一项随机、阳性对照、开放标签试验中，51 例 2 型糖尿病患者按 2:1 的比例随机分配接受恩格列净（10mg/天，n=31）或标准治疗（n=18）12 周。我们测量了 PAI-1 和纤溶酶-α2-抗纤溶酶复合物（PAP）的血浆浓度作为纤溶活性的指标。还测量了血清瘦素和高分子量（HMW）脂联素。
在完成试验的 49 例患者中，基线时 PAI-1 血浆浓度与体重、内脏脂肪面积（VFA）、γ-谷氨酰转肽酶（GGT）、瘦素和血小板计数呈正相关，与高密度脂蛋白胆固醇和 PAP 呈负相关。恩格列净组体重和 VFA 显著下降，而对照组无变化。恩格列净组 12 周时 GGT 血清水平显著下降，而对照组无变化。恩格列净组血清 HMW 脂联素显著升高。恩格列净组 PAI-1 血浆浓度显著下降 25%，而对照组无变化。恩格列净组 PAI-1 的变化与体重和瘦素的变化呈正相关，与 PAP 的变化呈负相关。
恩格列净通过降低血糖作用、减少 VFA 和恢复脂联素平衡，降低 PAI-1 血浆浓度。（临床试验注册号：UMIN000025418）。
