Department of Internal Medicine, Chungnam National University Hospital, Daejeon, Republic of Korea.
Department of Internal Medicine, Chungnam National University School of Medicine, Daejeon, Republic of Korea.
Medicine (Baltimore). 2022 Nov 25;101(47):e31691. doi: 10.1097/MD.0000000000031691.
A decade ago, systemic inflammation became widely recognized as an etiology of type 2 diabetes mellitus (T2DM) and complications thereof. Senescent CD8 + T cells of T2DM patients exhibit increased secretion of pro-inflammatory cytokines and enhanced expression of cytotoxic molecules, contributing to systemic inflammation. Recently, many anti-inflammatory roles played by statins and ezetimibe (cholesterol-lowering drugs) have been reported. We will explore the effects of statin/ezetimibe therapy on CD8 + T cell senescence in patients with T2DM and hypercholesterolemia.
This 2-group, parallel, randomized, controlled clinical trial will recruit 108 subjects with T2DM and low-density lipoprotein-cholesterol (LDL-C) levels ≥100 mg/dL and randomly assign them to rosuvastatin/ezetimibe and rosuvastatin groups at a 1:1 ratio. Blood samples will be drawn at baseline and after 12 weeks of medication. The primary outcomes will be the LDL-C-lowering effects after 12 weeks. The secondary outcomes will be changes in the senescent (CD28 - CD57+) CD8 + T cell proportions; the levels of circulating pro-inflammatory cytokines, cytotoxic molecules, interleukin-1, transforming growth factor-β, fasting glucose, and HbA1c; and biochemical indices of kidney, liver, and muscle function. Symptoms and signs of predictable adverse events (myopathy and hepatitis) will be routinely monitored.
We will evaluate the effects of statin/ezetimibe on CD8 + T cell senescence. Statin/ezetimibe may exert a beneficial immunomodulatory effect.
十年前，系统性炎症被广泛认为是 2 型糖尿病（T2DM）及其并发症的病因。T2DM 患者的衰老 CD8+T 细胞表现出促炎细胞因子分泌增加和细胞毒性分子表达增强，导致全身炎症。最近，报道了他汀类药物和依折麦布（降胆固醇药物）的许多抗炎作用。我们将探讨他汀类药物/依折麦布治疗对 T2DM 伴高胆固醇血症患者 CD8+T 细胞衰老的影响。
这项 2 组、平行、随机、对照临床试验将招募 108 名 T2DM 伴低密度脂蛋白胆固醇（LDL-C）水平≥100mg/dL 的患者，并以 1:1 的比例随机分为瑞舒伐他汀/依折麦布和瑞舒伐他汀组。将在基线和用药 12 周后采集血样。主要结局将是 12 周后 LDL-C 降低的效果。次要结局将是衰老（CD28-CD57+）CD8+T 细胞比例的变化；循环促炎细胞因子、细胞毒性分子、白细胞介素-1、转化生长因子-β、空腹血糖和 HbA1c 的水平；以及肾功能、肝功能和肌肉功能的生化指标的变化。将常规监测可预测不良事件（肌病和肝炎）的症状和体征。
我们将评估他汀类药物/依折麦布对 CD8+T 细胞衰老的影响。他汀类药物/依折麦布可能发挥有益的免疫调节作用。
