Shalaby Youssef M, Nakhal Mohammed Moutaz, Afandi Bachar, Al-Zohily Bashar, Majed Lina, Kumar Kukkala Kiran, Emerald Bright Starling, Sadek Bassem, Akour Amal, Akawi Nadia
Department of Genetics and Genomics, College of Medicine and Health Sciences, United Arab Emirates University, Al-Ain, UAE.
Department of Pharmacology, College of Medicine and Health Sciences, United Arab Emirates University, Al-Ain, UAE.
Ann Med. 2025 Dec;57(1):2496795. doi: 10.1080/07853890.2025.2496795. Epub 2025 Apr 28.
Aging is a complex biological process marked by the decline of physiological functions and heightened susceptibility to chronic illnesses, notably cardiometabolic disorders. Ceramides (Cer) are lipid derivatives linked to aging and metabolic diseases. Sodium-Glucose Cotransporter-2 inhibitors (SGLT2i), widely used in managing type 2 diabetes, have an unclear impact on aging biomarkers and Cer profiles.
This study explored the association between SGLT2i use, plasma Cer levels (CerC16:0, CerC18:0, CerC22:0, CerC24:0, and CerC24:1), and aging biomarkers-Human Insulin-Like Growth Factor 1 (IGF-1), mammalian target of rapamycin (mTOR), 5-Methylcytosine (5MC), and Human H2AFX (Histone H2AX) in patients with type 2 diabetes mellitus (T2DM).
In this retrospective study, 95 participants were divided into three groups: patients on SGLT2i ( = 34), patients on non-SGLT2i anti-diabetic treatments ( = 36), and healthy controls ( = 25). Plasma Cer and aging biomarkers were quantified using Liquid Chromatography with tandem mass spectrometry (LC-MS-MS) and ELISA, respectively. Principal component analysis (PCA) assessed group-based clustering, while ANCOVA evaluated group differences with confounder adjustment.
SGLT2i-treated patients showed significantly lower CerC16:0, CerC22:0, and CerC24:1 levels ( < 0.01) and decreased 5MC and H2AX ( < 0.05) compared to non-SGLT2i patients. IGF-1 was significantly elevated in the SGLT2i group ( < 0.01), suggesting a possible protective effect on metabolic health. PCA distinguished control from diabetic groups but revealed overlap between SGLT2i and non-SGLT2i groups.
Beyond glucose control, SGLT2i may improve plasma Cer and aging markers in diabetic patients, supporting their broader therapeutic potential in aging and age-related diseases. Further large-scale studies are warranted to confirm these effects and underlying mechanisms.
衰老为一复杂生物学过程，其特征在于生理功能衰退以及对慢性病（尤其是心脏代谢紊乱）的易感性增加。神经酰胺（Cer）为与衰老和代谢疾病相关的脂质衍生物。钠-葡萄糖协同转运蛋白2抑制剂（SGLT2i）广泛用于治疗2型糖尿病，但其对衰老生物标志物和神经酰胺谱的影响尚不清楚。
本研究探讨了2型糖尿病（T2DM）患者使用SGLT2i、血浆神经酰胺水平（神经酰胺C16:0、神经酰胺C18:0、神经酰胺C22:0、神经酰胺C24:0和神经酰胺C24:1）与衰老生物标志物——人胰岛素样生长因子1（IGF-1）、雷帕霉素靶蛋白（mTOR）、5-甲基胞嘧啶（5MC）和人H2AFX（组蛋白H2AX）之间的关联。
在这项回顾性研究中，95名参与者被分为三组：使用SGLT2i的患者（n = 34）、使用非SGLT2i抗糖尿病治疗的患者（n = 36）和健康对照组（n = 25）。分别使用液相色谱串联质谱法（LC-MS-MS）和酶联免疫吸附测定法（ELISA）对血浆神经酰胺和衰老生物标志物进行定量分析。主成分分析（PCA）评估基于组的聚类情况，而协方差分析（ANCOVA）评估经混杂因素调整后的组间差异。
与未使用SGLT2i的患者相比，使用SGLT2i治疗的患者神经酰胺C16:0、神经酰胺C22:0和神经酰胺C24:1水平显著降低（P < 0.01），5MC和H2AX水平也降低（P < 0.05）。SGLT2i组的IGF-1显著升高（P < 0.01），提示其可能对代谢健康具有保护作用。PCA区分了对照组与糖尿病组，但显示SGLT2i组和非SGLT2i组之间存在重叠。
除血糖控制外，SGLT2i可能改善糖尿病患者的血浆神经酰胺和衰老标志物，支持其在衰老及与年龄相关疾病方面具有更广泛的治疗潜力。有必要开展进一步的大规模研究以证实这些作用及其潜在机制。
