Background:Frailty is a multidimensional condition often diagnosed in older adults with hypertension and diabetes, and both these conditions are associated with endothelial dysfunction and oxidative stress. We investigated the functional role of the SGLT2 (sodium glucose cotransporter 2) inhibitor empagliflozin in frail diabetic and hypertensive older adults.Methods:We studied the effects of empagliflozin in consecutive hypertensive and diabetic older patients with frailty presenting at the ASL (local health unit of the Italian Ministry of Health) of Avellino, Italy, from March 2021 to January 2022. Moreover, we performed in vitro experiments in human endothelial cells to measure cell viability, permeability, mitochondrial Ca²⁺, and oxidative stress.Results:We evaluated 407 patients; 325 frail elders with diabetes successfully completed the study. We propensity-score matched 75 patients treated with empagliflozin and 75 with no empagliflozin. We observed a correlation between glycemia and Montreal Cognitive Assessment (MoCA) score and between glycemia and 5-meter gait speed (5mGS). At 3-month follow-up, we detected a significant improvement in the MoCA score and in the 5mGS in patients receiving empagliflozin compared with non-treated subjects. Mechanistically, we demonstrate that empagliflozin significantly reduces mitochondrial Ca²⁺ overload and reactive oxygen species production triggered by high glucose in human endothelial cells, attenuates cellular permeability, and improves cell viability in response to oxidative stress.Conclusions:Taken together, our data indicate that empagliflozin reduces frailty in diabetic and hypertensive patients, most likely by decreasing the mitochondrial generation of reactive oxygen species in endothelial cells.

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通过恩格列净抑制 SGLT2 可改善内皮功能并减少线粒体氧化应激：来自虚弱高血压和糖尿病患者的见解

背景：虚弱是一种多维疾病，通常在患有高血压和糖尿病的老年人中被诊断出来，这两种疾病都与内皮功能障碍和氧化应激有关。我们研究了 SGLT2（钠葡萄糖协同转运蛋白 2）抑制剂恩格列净对体弱的糖尿病和高血压老年人的功能作用。方法：我们研究了恩格列净对在 ASL（当地卫生单位）连续出现虚弱的高血压和糖尿病老年患者的作用。 2021 年 3 月至 2022 年 1 月，意大利阿韦利诺的意大利卫生部）。此外，我们在人内皮细胞中进行了体外实验，以测量细胞活力、通透性、线粒体 Ca 2+ 和氧化应激。结果：我们评估^了407患者; 325 名患有糖尿病的体弱老人成功完成了这项研究。我们对 75 名接受恩格列净治疗的患者和 75 名未接受恩格列净治疗的患者进行了倾向评分匹配。我们观察到血糖与蒙特利尔认知评估 (MoCA) 评分以及血糖与 5 米步态速度 (5mGS) 之间的相关性。在 3 个月的随访中，我们发现与未接受治疗的受试者相比，接受恩格列净的患者 MoCA 评分和 5mGS 显着改善。从机制上讲，我们证明恩格列净可显着降低人内皮细胞中由高葡萄糖引发的线粒体 Ca ²⁺过载和活性氧的产生，减弱细胞通透性，并提高细胞响应氧化应激的活力。结论：综上所述，我们的数据表明恩格列净可减轻糖尿病和高血压患者的虚弱症状，最有可能是通过减少内皮细胞线粒体中活性氧的产生。