Zainordin Nur Aisyah, Hatta Sharifah Faradilla Wan Muhamad, Mohamed Shah Fatimah Zaherah, Rahman Thuhairah Abdul, Ismail Nurhuda, Ismail Zaliha, Abdul Ghani Rohana
Endocrine Unit, Department of Internal Medicine, Faculty of Medicine, University Teknologi MARA (UiTM), Selangor, Malaysia.
Pathology Diagnostic and Research Laboratories (CPDRL) Faculty of Medicine University Teknologi MARA (UiTM), Sg Buloh Campus, Selangor, Malaysia.
J Endocr Soc. 2019 Nov 19;4(1):bvz017. doi: 10.1210/jendso/bvz017. eCollection 2020 Jan 1.
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).
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.
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%, = 0.042 and ΔFBG vs -0.73 ± 4.55 mmol/L vs -1.90 ± 4.40 mmol/L, = 0.015, respectively). The placebo group showed worsening of ΔFMD while the dapagliflozin group maintained similar measurements pre- and posttherapy ( = not significant). There was a reduction in ICAM-1 levels in the dapagliflozin group (-83.9 ± 205.9 ng/mL, < 0.02), which remained unchanged in the placebo group (-11.0 ± 169.1 ng/mL, = 0.699). Univariate correlation analysis revealed a significant negative correlation between HbA1c and ΔFMD within the active group.
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.
评估钠-葡萄糖协同转运蛋白2抑制剂（SGLT2-I）达格列净对高危2型糖尿病（T2DM）患者内皮功能的影响。
这是一项前瞻性、双盲、随机、安慰剂对照的临床试验，研究对象为患有潜在缺血性心脏病且正在接受二甲双胍和胰岛素治疗的T2DM患者（n = 81）。在接受达格列净（n = 40）或安慰剂（n = 41）额外治疗12周后，通过血流介导的血管舒张变化（ΔFMD）、硝酸甘油介导的血管舒张变化（ΔNMD）以及包括细胞间黏附分子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）]在内的替代标志物评估全身内皮功能。还测量了血糖和血脂水平。
与安慰剂组相比，达格列净组的糖化血红蛋白（HbA1c）和空腹血糖（FBG）显著降低（ΔHbA1c -0.83±1.47% 对 -0.16±1.25%，P = 0.042；ΔFBG对 -0.73±4.
