Effects of Dapagliflozin on Endothelial Dysfunction in Type 2 Diabetes With Established Ischemic Heart Disease (EDIFIED)
Effects of Dapagliflozin on Endothelial Dysfunction in Type 2 Diabetes With Established Ischemic Heart Disease (EDIFIED)
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DOI：
10.1210/jendso/bvz017
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发表时间：
2019-11
影响因子：
4.1
通讯作者：
Nur Aisyah Zainordin;S. F. W. M. Hatta;F. Z. Mohamed Shah;T. Rahman;N. Ismail;Z. Ismail;R. Abdul Ghani
中科院分区：
文献类型：
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作者：
Nur Aisyah Zainordin;S. F. W. M. Hatta;F. Z. Mohamed Shah;T. Rahman;N. Ismail;Z. Ismail;R. Abdul Ghani
摘要目的评价钠-葡萄糖协同转运蛋白2抑制剂（SGLT 2-I）达格列净对高危2型糖尿病（T2 DM）患者血管内皮功能的影响。方法这是一项前瞻性、双盲、随机、安慰剂对照的临床试验，在接受二甲双胍和胰岛素治疗的合并基础缺血性心脏病的T2 DM患者中进行（n = 81）。在使用达格列净（n = 40）或安慰剂（n = 41）进行额外治疗12周后，通过血流介导的扩张（ΔFMD）变化、硝酸甘油介导的扩张（ΔNMD）变化和替代标志物（包括细胞间粘附分子1（ICAM-1）、内皮型一氧化氮合酶（eNOS）、高敏C反应蛋白（hs-CRP）、和脂蛋白（a）（Lp[a]）。还测量了甘油和脂质谱。结果与安慰剂组相比，达格列净组糖化血红蛋白（HbA 1c）和空腹血糖（FBG）均显著降低（Δ HbA 1c为-0.83 ± 1.47% vs -0.16 ± 1.25%，P = 0.042; ΔFBG为-0.73 ± 4.55 mmol/L vs -1.90 ± 4.40 mmol/L，P = 0.015）。安慰剂组显示ΔFMD恶化，而达格列净组在治疗前后保持相似的测量值（P =不显著）。达格列净组ICAM-1水平降低（-83.9 ± 205.9 ng/mL，P < 0.02），安慰剂组ICAM-1水平保持不变（-11.0 ± 169.1 ng/mL，P = 0.699）。单因素相关分析显示，活动组HbA 1c与ΔFMD呈显著负相关。结论：在胰岛素和二甲双胍治疗的基础上，对高危患者进行12周的达格列净治疗，可显著降低HbA 1c、FBG和内皮功能的替代标志物。尽管达格列净组显示HbA 1c降低与FMD改善之间存在显著相关性，但两组之间的FMD无显著差异。
Abstract Objectives To evaluate the effect of the sodium-glucose cotransporter 2 inhibitor (SGLT2-I) dapagliflozin on endothelial function in patients with high-risk type 2 diabetes mellitus (T2DM). Methods This was a prospective, double-blind, randomized, placebo-controlled, clinical trial of patients with T2DM with underlying ischemic heart disease who were receiving metformin and insulin therapy (n = 81). After 12-weeks of additional therapy with either dapagliflozin (n = 40) or placebo (n = 41), systemic endothelial function was evaluated by change in flow-mediated dilation (ΔFMD), change in nitroglycerin-mediated dilation (ΔNMD) and surrogate markers including intercellular adhesion molecule 1 (ICAM-1), endothelial nitric oxide synthase (eNOS), high-sensitivity C-reactive protein (hs-CRP), and lipoprotein(a) (Lp[a]). Glycemic and lipid profiles were also measured. Results The dapagliflozin group demonstrated significant reductions of hemoglobin A1c (HbA1c) and fasting blood glucose (FBG) compared to the placebo group (ΔHbA1c –0.83 ± 1.47% vs –0.16 ± 1.25%, P = 0.042 and ΔFBG vs –0.73 ± 4.55 mmol/L vs –1.90 ± 4.40 mmol/L, P = 0.015, respectively). The placebo group showed worsening of ΔFMD while the dapagliflozin group maintained similar measurements pre- and posttherapy (P = not significant). There was a reduction in ICAM-1 levels in the dapagliflozin group (–83.9 ± 205.9 ng/mL, P < 0.02), which remained unchanged in the placebo group (–11.0 ± 169.1 ng/mL, P = 0.699). Univariate correlation analysis revealed a significant negative correlation between HbA1c and ΔFMD within the active group. Conclusion A 12-week therapy with dapagliflozin, in addition to insulin and metformin therapies, in high-risk patients resulted in significant reductions in HbA1c, FBG, and surrogate markers of the endothelial function. Although the dapagliflozin group demonstrated a significant association between reduction in HbA1c and improvement in FMD, there was no significant difference in FMD between the 2 groups.