Dapagliflozin reduces systemic inflammation in patients with type 2 diabetes without known heart failure

作者：Dennis D. Wang, Anna Naumova, Daniel Isquith, Jamie Sapp, Kim Anh Huynh, Isabella Tucker, Niranjan Balu, Anna Voronyuk, Baocheng Chu, Karen Ordovás, Charles Maynard, Rong Tian, Xue‐Qiao Zhao, Francis Kim · 发表于：Cardiovascular Diabetology · 年份：2024 · DOI：10.1186/s12933-024-02294-z · 被引用次数：46 · 研究领域：Cardiovascular Function and Risk Factors、Diabetes Treatment and Management、Cardiac Fibrosis and Remodeling

Abstract Objective 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. Research and design methods 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. Results 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 6 cells, P = 0.0497 ...