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移植后糖尿病:老年人的风险降低策略

Post-transplant diabetes mellitus: risk reduction strategies in the elderly.

作者信息

Duclos Alain, Flechner Lawrence M, Faiman Charles, Flechner Stuart M

机构信息

Transplant Center/Glickman Urological Institute, Cleveland Clinic Foundation, Cleveland, Ohio 44195, USA.

出版信息

Drugs Aging. 2006;23(10):781-93. doi: 10.2165/00002512-200623100-00002.

Abstract

New-onset diabetes mellitus in a previously non-diabetic transplant recipient is a serious adverse event that confers significant morbidity and mortality. The most significant consequences of post-transplant diabetes mellitus (PTDM) in solid organ transplant recipients include decreased patient and graft survival, an increased risk of infectious complications, and morbid cardiovascular events. The development of PTDM in the elderly is of particular concern because this group is already at increased risk of progression of cardiovascular disease. Because the elderly, especially those aged >65 years, are the fastest-growing segment of the renal transplant population, attention needs to be given to PTDM risk reduction and post-transplant management. PTDM develops as a consequence of both impaired insulin production and enhanced peripheral insulin resistance. A number of non-modifiable factors such as age, race, family history, hepatitis C, polycystic kidney disease and emerging genetic causes have been identified as risk factors for PTDM. However, a number of modifiable factors can be targets for intervention in high-risk patients, including bodyweight (through dietary restriction and exercise), hypertension, hyperlipidaemia and the effects of certain immunosuppressive agents. The two agents most responsible for PTDM are tacrolimus and corticosteroids, especially when used in combination. Attempts to modify doses and regimens designed to eliminate or avoid these drugs should be considered. Use of HMG-CoA reductase inhibitors ('statins') and ACE inhibitors is particularly helpful in controlling hypertension and hyperlipidaemia in the elderly because these agents confer protection against future adverse cardiovascular events. Bisphosphonates are also advantageous in controlling the progression of osteoporosis and possible increased risk of bone fractures. Future trials in the elderly should focus on such endpoints as PTDM, post-transplant neoplasia, cardiovascular events and bone fracture events in order to identify the safest regimens that provide the optimal control of rejection while limiting the morbidity from these secondary events.

摘要

既往无糖尿病的移植受者新发糖尿病是一种严重的不良事件,会导致显著的发病率和死亡率。实体器官移植受者发生移植后糖尿病(PTDM)的最严重后果包括患者和移植物存活率降低、感染并发症风险增加以及严重心血管事件。老年人发生PTDM尤其值得关注,因为这一群体心血管疾病进展风险本来就更高。由于老年人,尤其是年龄>65岁的老年人,是肾移植人群中增长最快的部分,因此需要关注降低PTDM风险及移植后的管理。PTDM是胰岛素生成受损和外周胰岛素抵抗增强共同作用的结果。一些不可改变的因素,如年龄、种族、家族史、丙型肝炎、多囊肾病和新出现的遗传原因,已被确定为PTDM的危险因素。然而,一些可改变的因素可以成为高危患者干预的目标,包括体重(通过饮食限制和运动)、高血压、高脂血症以及某些免疫抑制剂的影响。导致PTDM最主要的两种药物是他克莫司和皮质类固醇,尤其是两者联合使用时。应考虑尝试调整剂量和用药方案以减少或避免使用这些药物。使用HMG-CoA还原酶抑制剂(“他汀类药物”)和ACE抑制剂对控制老年人的高血压和高脂血症特别有帮助,因为这些药物可预防未来的不良心血管事件。双膦酸盐在控制骨质疏松症进展和可能增加的骨折风险方面也具有优势。未来针对老年人的试验应关注PTDM、移植后肿瘤形成、心血管事件和骨折事件等终点,以便确定在限制这些继发事件发病率的同时能提供最佳排斥反应控制的最安全用药方案。

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