The Origin of New-Onset Diabetes After Liver Transplantation: Liver, Islets, or Gut?
The Origin of New-Onset Diabetes After Liver Transplantation: Liver, Islets, or Gut?
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肝移植后新发糖尿病的根源：肝脏、胰岛还是肠道？
DOI：
10.1097/tp.0000000000001111
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发表时间：
2016-04-01
期刊：
影响因子：
6.2
通讯作者：
Zheng, Shusen
中科院分区：
文献类型：
--
作者：
Ling, Qi;Xu, Xiao;Zheng, Shusen
新发糖尿病是实体器官移植后常见的并发症。尽管该疾病与一些常见因素相关，包括受者年龄、体重指数、丙型肝炎感染以及免疫抑制药物的使用，但肝移植后新发糖尿病（NODALT）具有以下独特之处，因此应将其视为一种独立的病症。首先，肝移植后，移植肝脏成为患者主要的代谢调节器官，而肾移植或其他器官移植则并非如此。移植物的代谢状态以及遗传学特征在NODALT的发生发展中起着关键作用。其次，朗格汉斯胰岛功能障碍在肝硬化患者中较为常见，且免疫抑制剂（尤其是钙调神经磷酸酶抑制剂）会使其进一步恶化。另一方面，由于肝脏的耐受性（免疫赦免），在肝移植中广泛提倡采用最小化免疫抑制方案。第三也是最后一点，通过 “肠 - 肝轴”，移植物功能与肠道微生物群密切相关，肠道微生物群如今被视为一个重要的代谢器官，且已知其可独立影响宿主的代谢稳态。肝移植受者具有特定的肠道微生物群，可能易于引发代谢紊乱。在本综述中，我们提出NODALT可能起源于肝脏、胰岛和肠道这3个部位，以帮助阐明NODALT的潜在发病机制。
Abstract New-onset diabetes is a frequent complication after solid organ transplantation. Although a number of common factors are associated with the disease, including recipient age, body mass index, hepatitis C infection, and use of immunosuppressive drugs, new-onset diabetes after liver transplantation (NODALT) has the following unique aspects and thus needs to be considered its own entity. First, a liver graft becomes the patient's primary metabolic regulator after liver transplantation, but this would not be the case for kidney or other grafts. The metabolic states, as well as the genetics of the graft, play crucial roles in the development of NODALT. Second, dysfunction of the islets of Langerhans is common in cirrhotic patients and would be exacerbated by immunosuppressive agents, particularly calcineurin inhibitors. On the other hand, minimized immunosuppressive protocols have been widely advocated in liver transplantation because of liver tolerance (immune privilege). Third and last, through the “gut-liver axis,” graft function is closely linked to gut microbiota, which is now considered an important metabolic organ and known to independently influence the host's metabolic homeostasis. Liver transplant recipients present with specific gut microbiota that may be prone to trigger metabolic disorders. In this review, we proposed 3 possible sites for the origin of NODALT, which are liver, islets, and gut, to help elucidate the underlying mechanism of NODALT.