恩格列净对合并2型糖尿病和冠状动脉疾病患者炎症标志物的影响：恩格列净治疗冠状动脉疾病（EMPA-CARD）随机对照试验

The effect of EMPAgliflozin on markers of inflammation in patients with concomitant type 2 diabetes mellitus and Coronary ARtery Disease: the EMPA-CARD randomized controlled trial.

作者信息

Gohari Sepehr, Reshadmanesh Tara, Khodabandehloo Hadi, Karbalaee-Hasani Amir, Ahangar Hassan, Arsang-Jang Shahram, Ismail-Beigi Faramarz, Dadashi Mohsen, Ghanbari Samin, Taheri Homa, Fathi Mojtaba, Muhammadi Muhammad Javad, Mahmoodian Reyhaneh, Asgari Atieh, Tayaranian Mohammadreza, Moharrami Mehdi, Mahjani Mahsa, Ghobadian Bijan, Chiti Hossein, Gohari Sheida

机构信息

Student Research Center, School of Medicine, Zanjan University of Medical Sciences, Zanjan, Iran.

Department of Family Medicine, Alborz University of Medical Science, Karaj, Alborz, Iran.

出版信息

Diabetol Metab Syndr. 2022 Nov 17;14(1):170. doi: 10.1186/s13098-022-00951-5.

Systemic inflammation and oxidative burden in patients with type 2 diabetes mellitus (T2DM) causes deleterious cardiovascular outcomes. We sought to investigate the clinical antioxidative and anti-inflammatory effects of empagliflozin. Platelet function, oxidant and antioxidant biomarkers and pro-inflammatory agents at baseline and at 26 weeks were measured. A total of 95 patients (41.05% male, mean age 62.85 ± 7.91 years, mean HbA 7.89 ± 0.96%) with concomitant T2DM and coronary artery disease (CAD) were randomized (1:1) to receive empagliflozin (10 mg/daily) or placebo. Patients treated with empagliflozin had lower levels of interleukin 6 (IL-6) (adjusted difference (adiff): - 1.06 pg/mL, 95% CI - 1.80; - 0.32, P = 0.006), interleukin 1β (IL-1β) and high-sensitive C-reactive protein (Hs-CRP) (adiff: - 4.58 pg/mL and - 2.86 mg/L; P = 0.32 and 0.003, respectively) compared to placebo. There were elevations in super oxidase dismutase (SOD) activity, glutathione (GSHr), and total antioxidant capacity (TAC) with empagliflozin (adiff: 3.7 U/mL, 0.57 muM, and 124.08 mmol/L, 95% CI 1.36; 6.05, 0.19; 0.95, and 47.98; 200.18, P = 0.002, 0.004, and 0.002, respectively). While reactive oxygen species (ROS) improved significantly (adiff: - 342.51, 95% CI - 474.23; - 210.79, P < 0.001), the changes in catalase activity (CAT), malondialdehyde (MDA), or protein carbonyl groups (PCG) were not significant. Moreover, the P-selectin antigen expression on platelet surface was significantly reduced (adiff: - 8.81, 95% CI - 14.87; - 2.75, P = 0.005). Markers of glycemic status (fasting blood glucose, HbA, and HOMA-IR (homeostatic model assessment for insulin resistance) significantly improved (P < 0.001). Among patients with T2DM and CAD, 6-month treatment with empagliflozin can mitigate inflammation, platelet activity and oxidative stress and is associated with clinical cardiovascular benefits.Trial Registration Iranian Registry of Clinical Trials. www.IRCT.ir , Identifier: IRCT20190412043247N2. Registration Date: 6/13/2020. Registration timing: prospective.

2型糖尿病（T2DM）患者的全身炎症和氧化负担会导致有害的心血管结局。我们旨在研究恩格列净的临床抗氧化和抗炎作用。测量了基线和26周时的血小板功能、氧化剂和抗氧化生物标志物以及促炎因子。共有95例伴有T2DM和冠状动脉疾病（CAD）的患者（男性占41.05%，平均年龄62.85±7.91岁，平均糖化血红蛋白7.89±0.96%）被随机（1:1）分为接受恩格列净（10mg/每日）或安慰剂治疗。与安慰剂相比，接受恩格列净治疗的患者白细胞介素6（IL-6）水平较低（校正差异（adiff）：-1.06pg/mL，95%CI-1.80；-0.32，P=0.006），白细胞介素1β（IL-1β）和高敏C反应蛋白（Hs-CRP）水平较低（adiff分别为-4.58pg/mL和-2.86mg/L；P分别为0.32和0.003）。恩格列净治疗后超氧化物歧化酶（SOD）活性、谷胱甘肽（GSHr）和总抗氧化能力（TAC）升高（adiff分别为3.7U/mL、0.57μM和124.08mmol/L，95%CI分别为1.36；6.05、0.19；0.95和47.98；200.18，P分别为0.002、0.004和0.002）。虽然活性氧（ROS）显著改善（adiff：-342.51，95%CI-474.23；-210.79，P<0.001），但过氧化氢酶活性（CAT）、丙二醛（MDA）或蛋白质羰基（PCG）的变化不显著。此外，血小板表面P-选择素抗原表达显著降低（adiff：-8.81，95%CI-14.87；-2.75，P=0.005）。血糖状态标志物（空腹血糖、糖化血红蛋白和HOMA-IR（胰岛素抵抗稳态模型评估）显著改善（P<0.001）。在T2DM和CAD患者中，恩格列净治疗6个月可减轻炎症、血小板活性和氧化应激，并具有临床心血管益处。试验注册：伊朗临床试验注册中心。www.IRCT.ir，标识符：IRCT20190412043247N2。注册日期：2020年6月13日。注册时间：前瞻性。