Cardiovasc Diabetol:残余脂蛋白胆固醇与肾移植受者移植后新发糖尿病(NODAT)相关

2022-04-25 从医路漫漫 MedSci原创

随着肾移植受者存活率(RTR)的不断提高和免疫抑制方案的改进,肾移植后长期稳定病程的慢性并发症在临床上变得越来越重要。

背景:就成本效益、提高生活质量、降低发病率和死亡率而言,肾移植是终末期肾病患者的首选治疗方案。随着肾移植受者存活率(RTR)的不断提高和免疫抑制方案的改进,肾移植后长期稳定病程的慢性并发症在临床上变得越来越重要。移植后新发糖尿病(NODAT)就是这样一种相关情况,可能影响高达50%的RTR。NODAT与更差的患者和移植物结果相关,反映在心血管事件和慢性移植物衰竭的风险增加。在美国,NODAT还显著增加了移植后护理的年费用,估计移植后第一年为12000美元,随后几年为19000美元。尽管该主题具有临床重要性,但有利于NODAT发展的病理生理学机制仍未得到充分探索,因此目前定义预测性生物标志物的尝试具有有限的实际相关性。诺达特和二型糖尿病的病理生理学的共同点似乎是β细胞的正常功能。

然而,β细胞对胆固醇平衡的紊乱很敏感。通过吸收低密度脂蛋白使β细胞胆固醇负荷,使其功能失调,并损害胰岛素分泌。这些观察可以解释为什么使用他汀类药物,增加β细胞上低密度脂蛋白受体的表达,与2型糖尿病风险增加相关。事实上,我们最近发现,在RTR中使用他汀类药物也会增加患NODAT的风险。另一方面,受损的高密度脂蛋白介导的胆固醇流出,一种卸载细胞胆固醇的机制,似乎也导致功能失调的β细胞。与这些数据相一致,我们在最近的观察工作中报道,低基线HDL介导的胆固醇流出量显著增加了随访期间RTR中发生NODAT的风险。除了低密度脂蛋白和高密度脂蛋白,残余脂蛋白(RLP)胆固醇代表了一个新兴的亚类,不仅与心血管疾病的高发病率相关,而且与总死亡率和全身炎症的增加相关。残留物是肝源性极低密度脂蛋白和肠源性乳糜微粒的不完全脂解残留物。可以想象,残留物可能比低密度脂蛋白对β细胞的损害更大,因为它们通过清道夫受体以不受控制的方式被吸收。然而,到目前为止,还没有临床上探索这种假设的数据。因此,目前的研究旨在测试RLP胆固醇的RTR基线水平是否与NODAT事件的风险相关。

方法:这项纵向队列研究包括480名基线时无糖尿病的RTR。在中位数为5.2年[4.1-5.8年]的随访期间,53例患者(11%)被诊断为NODAT。通过从总胆固醇值中减去HDL和LDL胆固醇来计算RLP胆固醇(都是直接测量的)。

结果:随后发展为NODAT的RTR的基线残余胆固醇值明显较高(0.9[0.5–1.2]mmol/L对0.6[0.4–0.9]mmol/L,p = 0.001)。Kaplan-Meier分析显示,较高的RLP胆固醇值与NODAT事件风险增加相关(对数秩检验,p < 0.001)。Cox回归分析显示,基线RLP胆固醇水平与NODAT (HR,2.27[1.64–3.14]每1 SD增加,p < 0.001)之间存在显著的纵向相关性,这种相关性在校正血浆葡萄糖和HbA1c (p = 0.002)、HDL和LDL胆固醇(p = 0.008)以及使用免疫抑制药物(p < 0.001)等因素后仍然存在。将基线残余胆固醇加入Framingham糖尿病风险评分显著改善了NODAT预测(C统计值变化,p = 0.01)。

图1 Kaplan–Meier分析(对数秩检验:p = 0.01)

表1 Cox回归分析确定的RLP胆固醇水平增加1 mmol/l与NODAT事件的相关性

图2根据残余脂蛋白胆固醇(RLP C)水平的NODAT发生概率。概率由Cox回归分析确定,使用四个节点的三次样条。请注意y轴的对数刻度。a粗略分析,B根据年龄和性别进行调整,C根据年龄、性别和糖化血红蛋白进行调整,D根据年龄、性别、糖化血红蛋白和体重指数进行调整(身体质量指数)。结位于0.1、0.5、0.8和1.5毫摩尔/升

表2添加和不添加RLP胆固醇的Framingham糖尿病风险评分的逻辑回归分析

结论:这项研究表明,基线RLP胆固醇水平与NODAT事件密切相关,独立于其他几个公认的危险因素。

原文出处:Szili-Torok T,  Sokooti S,  Osté MCJ, et al.Remnant lipoprotein cholesterol is associated with incident new onset diabetes after transplantation (NODAT) in renal transplant recipients: results of the TransplantLines Biobank and cohort Studies.Cardiovasc Diabetol 2022 Mar 16;21(1)

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    2022-08-08 docwu2019
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    2022-11-18 quxin068
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