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心脏移植后依维莫司治疗的代谢后果:一个产生假说的研究。

Metabolic Sequelae of Everolimus Treatment After Cardiac Transplant: A Hypothesis-Generating Study.

机构信息

Department of Diabetes and Endocrinology, St Vincent's Hospital, Sydney, NSW, Australia; Clinical Diabetes, Appetite and Metabolism Laboratory, Garvan Institute of Medical Research, Sydney, NSW, Australia; School of Clinical Medicine, St Vincent's Campus, Faculty of Medicine and Health, University of New South Wales, Sydney, NSW, Australia.

Department of Diabetes and Endocrinology, St Vincent's Hospital, Sydney, NSW, Australia; School of Clinical Medicine, St Vincent's Campus, Faculty of Medicine and Health, University of New South Wales, Sydney, NSW, Australia.

出版信息

Heart Lung Circ. 2023 Sep;32(9):1076-1079. doi: 10.1016/j.hlc.2023.05.014. Epub 2023 Jun 22.

Abstract

BACKGROUND

Although modern immunosuppressants improve survival post-transplant, they are associated with long-term metabolic complications, such as post-transplant diabetes mellitus (PTDM). Calcineurin inhibitor-sparing regimens using everolimus attenuate some complications such as left ventricular hypertrophy. However, the metabolic effects of everolimus following transplant are less clear.

METHODS

Post-hoc analysis to compare PTDM and other metabolic outcomes in participants of a randomised open-label clinical trial of low-dose everolimus and tacrolimus versus standard-dose tacrolimus in heart transplant recipients (RADTAC study).

RESULTS

There were 39 participants in the trial; mean follow-up was 6.4±1.5 years. There was a high rate of pre-existing diabetes (26%) and newly diagnosed PTDM (36%) during follow-up. Half the patients who developed PTDM in the everolimus-tacrolimus group (n=4/8) ceased diabetes medications during follow-up, which was not observed in patients on standard tacrolimus (n=0/6). In the first 12 months there was a higher use of non-insulin treatment for diabetes in the everolimus-tacrolimus group compared to the standard tacrolimus group.

CONCLUSIONS

This study suggests that treatment with everolimus may be associated with improved glycaemic control of PTDM relative to treatment with standard doses of calcineurin inhibitor. These findings should be further studied in prospective randomised trials.

摘要

背景

虽然现代免疫抑制剂可提高移植后的存活率,但它们与长期代谢并发症有关,如移植后糖尿病(PTDM)。使用依维莫司的钙调神经磷酸酶抑制剂节约方案可减轻左心室肥厚等并发症。然而,移植后依维莫司的代谢影响尚不清楚。

方法

对心脏移植受者接受低剂量依维莫司和他克莫司与标准剂量他克莫司的随机开放标签临床试验(RADTAC 研究)中参与者的事后分析,以比较 PTDM 和其他代谢结果。

结果

试验中有 39 名参与者;平均随访时间为 6.4±1.5 年。在随访期间,有 26%的患者存在糖尿病前期,36%的患者新诊断为 PTDM。在依维莫司-他克莫司组中,4/8 名发生 PTDM 的患者在随访期间停止了糖尿病药物治疗,而在标准他克莫司组中,无 6/6 名患者出现这种情况。在最初的 12 个月中,依维莫司-他克莫司组中用于糖尿病的非胰岛素治疗的使用率高于标准他克莫司组。

结论

本研究表明,与使用标准剂量钙调神经磷酸酶抑制剂相比,依维莫司治疗可能与改善 PTDM 的血糖控制有关。这些发现应在前瞻性随机试验中进一步研究。

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