Division of Cardiology, Department of Medicine, University of Washington, Seattle, WA, USA.
Department of Radiology, University of Washington, Seattle, WA, USA.
Cardiovasc Diabetol. 2024 Jun 7;23(1):197. doi: 10.1186/s12933-024-02294-z.
Sodium glucose cotransporter 2 (SGLT2) inhibitors significantly improve cardiovascular outcomes in diabetic patients; however, the mechanism is unclear. We hypothesized that dapagliflozin improves cardiac outcomes via beneficial effects on systemic and cardiac inflammation and cardiac fibrosis.
This randomized placebo-controlled clinical trial enrolled 62 adult patients (mean age 62, 17% female) with type 2 diabetes (T2D) without known heart failure. Subjects were randomized to 12 months of daily 10 mg dapagliflozin or placebo. For all patients, blood/plasma samples and cardiac magnetic resonance imaging (CMRI) were obtained at time of randomization and at the end of 12 months. Systemic inflammation was assessed by plasma IL-1B, TNFα, IL-6 and ketone levels and PBMC mitochondrial respiration, an emerging marker of sterile inflammation. Global myocardial strain was assessed by feature tracking; cardiac fibrosis was assessed by T1 mapping to calculate extracellular volume fraction (ECV); and cardiac tissue inflammation was assessed by T2 mapping.
Between the baseline and 12-month time point, plasma IL-1B was reduced (- 1.8 pg/mL, P = 0.003) while ketones were increased (0.26 mM, P = 0.0001) in patients randomized to dapagliflozin. PBMC maximal oxygen consumption rate (OCR) decreased over the 12-month period in the placebo group but did not change in patients receiving dapagliflozin (- 158.9 pmole/min/10 cells, P = 0.0497 vs. - 5.2 pmole/min/10 cells, P = 0.41), a finding consistent with an anti-inflammatory effect of SGLT2i. Global myocardial strain, ECV and T2 relaxation time did not change in both study groups.
NCT03782259.
钠-葡萄糖共转运蛋白 2（SGLT2）抑制剂可显著改善糖尿病患者的心血管结局，但具体机制尚不清楚。我们假设达格列净通过对全身和心脏炎症以及心脏纤维化的有益作用来改善心脏结局。
这是一项随机、安慰剂对照的临床试验，共纳入 62 名年龄在 62 岁（女性占 17%）、无心力衰竭的 2 型糖尿病（T2D）成年患者。患者被随机分为 12 个月的每日 10 毫克达格列净或安慰剂组。所有患者在随机分组时和 12 个月时均采集血/血浆样本和心脏磁共振成像（CMRI）。通过血浆白细胞介素 1B（IL-1B）、肿瘤坏死因子-α（TNFα）、白细胞介素 6（IL-6）和酮体水平以及外周血单核细胞线粒体呼吸（一种新兴的无菌性炎症标志物）评估全身炎症。通过特征跟踪评估整体心肌应变；通过 T1 映射计算细胞外体积分数（ECV）评估心脏纤维化；通过 T2 映射评估心脏组织炎症。
与基线相比，在随机分组至达格列净组的患者中，血浆 IL-1B 降低（-1.8pg/mL，P=0.003），而酮体增加（0.26mM，P=0.0001）。在安慰剂组中，12 个月期间 PBMC 最大耗氧量（OCR）下降，但在接受达格列净治疗的患者中未发生变化（-158.9pmole/min/10 细胞，P=0.0497 与 -5.2pmole/min/10 细胞，P=0.41），这一发现与 SGLT2i 的抗炎作用一致。在两组研究中，整体心肌应变、ECV 和 T2 弛豫时间均未发生变化。
NCT03782259。
