title: The Origin of New-Onset Diabetes After Liver Transplantation: Liver, Islets, or Gut?
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.
authors.affiliation: 1 Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China. 2 Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, China. 3 State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
authors.forename: Qi
authors.initials: Q
authors.lastname: Ling
authors.forename: Xiao
authors.initials: X
authors.lastname: Xu
authors.forename: Baohong
authors.initials: B
authors.lastname: Wang
authors.forename: Lanjuan
authors.initials: L
authors.lastname: Li
authors.forename: Shusen
authors.initials: S
authors.lastname: Zheng
mesh_terms: D000818:Animals; D003920:Diabetes Mellitus / Q000209:etiology* / Q000276:immunology / Q000378:metabolism / Q000503:physiopathology / Q000628:therapy; D000069196:Gastrointestinal Microbiome; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects; D007413:Intestinal Mucosa / Q000378:metabolism*; D007422:Intestines / Q000276:immunology / Q000382:microbiology / Q000503:physiopathology; D007515:Islets of Langerhans / Q000276:immunology / Q000378:metabolism* / Q000503:physiopathology; D008099:Liver / Q000276:immunology / Q000378:metabolism* / Q000503:physiopathology / Q000601:surgery*; D016031:Liver Transplantation / Q000009:adverse effects*; D011379:Prognosis; D012307:Risk Factors
chemical_list: D007166:Immunosuppressive Agents