title: Minimizing tacrolimus decreases the risk of new-onset diabetes mellitus after liver transplantation.
abstract: OBJECTIVE
  To investigate the impact of minimum tacrolimus (TAC) on new-onset diabetes mellitus (NODM) after liver transplantation (LT).
  
  
  METHODS
  We retrospectively analyzed the data of 973 liver transplant recipients between March 1999 and September 2014 in West China Hospital Liver Transplantation Center. Following the exclusion of ineligible recipients, 528 recipients with a TAC-dominant regimen were included in our study. We calculated and determined the mean trough concentration of TAC (cTAC) in the year of diabetes diagnosis in NODM recipients or in the last year of the follow-up in non-NODM recipients. A cutoff of mean cTAC value for predicting NODM 6 mo after LT was identified using a receptor operating characteristic curve. TAC-related complications after LT was evaluated by χ(2) test, and the overall and allograft survival was evaluated using the Kaplan-Meier method. Risk factors for NODM after LT were examined by univariate and multivariate Cox regression.
  
  
  RESULTS
  Of the 528 transplant recipients, 131 (24.8%) developed NODM after 6 mo after LT, and the cumulative incidence of NODM progressively increased. The mean cTAC of NODM group recipients was significantly higher than that of recipients in the non-NODM group (7.66 ± 3.41 ng/mL vs 4.47 ± 2.22 ng/mL, P < 0.05). Furthermore, NODM group recipients had lower 1-, 5-, 10-year overall survival rates (86.7%, 71.3%, and 61.1% vs 94.7%, 86.1%, and 83.7%, P < 0.05) and allograft survival rates (92.8%, 84.6%, and 75.7% vs 96.1%, 91%, and 86.1%, P < 0.05) than the others. The best cutoff of mean cTAC for predicting NODM was 5.89 ng/mL after 6 mo after LT. Multivariate analysis showed that old age at the time of LT (> 50 years), hypertension pre-LT, and high mean cTAC (≥ 5.89 ng/mL) after 6 mo after LT were independent risk factors for developing NODM. Concurrently, recipients with a low cTAC (< 5.89 ng/mL) were less likely to become obese (21.3% vs 30.2%, P < 0.05) or to develop dyslipidemia (27.5% vs 44.8%, P <0.05), chronic kidney dysfunction (14.6% vs 22.7%, P < 0.05), and moderate to severe infection (24.7% vs 33.1%, P < 0.05) after LT than recipients in the high mean cTAC group. However, the two groups showed no significant difference in the incidence of acute and chronic rejection, hypertension, cardiovascular events and new-onset malignancy.
  
  
  CONCLUSIONS
  A minimal TAC regimen can decrease the risk of long-term NODM after LT. Maintaining a cTAC value below 5.89 ng/mL after LT is safe and beneficial.
authors.affiliation: Jiu-Lin Song, Wei Gao, Yan Zhong, Lu-Nan Yan, Jia-Yin Yang, Tian-Fu Wen, Bo Li, Wen-Tao Wang, Hong Wu, Ming-Qing Xu, Zhe-Yu Chen, Yong-Gang Wei, Li Jiang, Jian Yang, Department of Liver Surgery, Liver Transplantation Center, West China Hospital of Sichuan University, Chengdu 610041, Sichuan Province, China.
authors.forename: Jiu-Lin
authors.initials: JL
authors.lastname: Song
authors.affiliation: Jiu-Lin Song, Wei Gao, Yan Zhong, Lu-Nan Yan, Jia-Yin Yang, Tian-Fu Wen, Bo Li, Wen-Tao Wang, Hong Wu, Ming-Qing Xu, Zhe-Yu Chen, Yong-Gang Wei, Li Jiang, Jian Yang, Department of Liver Surgery, Liver Transplantation Center, West China Hospital of Sichuan University, Chengdu 610041, Sichuan Province, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Gao
authors.affiliation: Jiu-Lin Song, Wei Gao, Yan Zhong, Lu-Nan Yan, Jia-Yin Yang, Tian-Fu Wen, Bo Li, Wen-Tao Wang, Hong Wu, Ming-Qing Xu, Zhe-Yu Chen, Yong-Gang Wei, Li Jiang, Jian Yang, Department of Liver Surgery, Liver Transplantation Center, West China Hospital of Sichuan University, Chengdu 610041, Sichuan Province, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhong
authors.affiliation: Jiu-Lin Song, Wei Gao, Yan Zhong, Lu-Nan Yan, Jia-Yin Yang, Tian-Fu Wen, Bo Li, Wen-Tao Wang, Hong Wu, Ming-Qing Xu, Zhe-Yu Chen, Yong-Gang Wei, Li Jiang, Jian Yang, Department of Liver Surgery, Liver Transplantation Center, West China Hospital of Sichuan University, Chengdu 610041, Sichuan Province, China.
authors.forename: Lu-Nan
authors.initials: LN
authors.lastname: Yan
authors.affiliation: Jiu-Lin Song, Wei Gao, Yan Zhong, Lu-Nan Yan, Jia-Yin Yang, Tian-Fu Wen, Bo Li, Wen-Tao Wang, Hong Wu, Ming-Qing Xu, Zhe-Yu Chen, Yong-Gang Wei, Li Jiang, Jian Yang, Department of Liver Surgery, Liver Transplantation Center, West China Hospital of Sichuan University, Chengdu 610041, Sichuan Province, China.
authors.forename: Jia-Yin
authors.initials: JY
authors.lastname: Yang
authors.affiliation: Jiu-Lin Song, Wei Gao, Yan Zhong, Lu-Nan Yan, Jia-Yin Yang, Tian-Fu Wen, Bo Li, Wen-Tao Wang, Hong Wu, Ming-Qing Xu, Zhe-Yu Chen, Yong-Gang Wei, Li Jiang, Jian Yang, Department of Liver Surgery, Liver Transplantation Center, West China Hospital of Sichuan University, Chengdu 610041, Sichuan Province, China.
authors.forename: Tian-Fu
authors.initials: TF
authors.lastname: Wen
authors.affiliation: Jiu-Lin Song, Wei Gao, Yan Zhong, Lu-Nan Yan, Jia-Yin Yang, Tian-Fu Wen, Bo Li, Wen-Tao Wang, Hong Wu, Ming-Qing Xu, Zhe-Yu Chen, Yong-Gang Wei, Li Jiang, Jian Yang, Department of Liver Surgery, Liver Transplantation Center, West China Hospital of Sichuan University, Chengdu 610041, Sichuan Province, China.
authors.forename: Bo
authors.initials: B
authors.lastname: Li
authors.affiliation: Jiu-Lin Song, Wei Gao, Yan Zhong, Lu-Nan Yan, Jia-Yin Yang, Tian-Fu Wen, Bo Li, Wen-Tao Wang, Hong Wu, Ming-Qing Xu, Zhe-Yu Chen, Yong-Gang Wei, Li Jiang, Jian Yang, Department of Liver Surgery, Liver Transplantation Center, West China Hospital of Sichuan University, Chengdu 610041, Sichuan Province, China.
authors.forename: Wen-Tao
authors.initials: WT
authors.lastname: Wang
authors.affiliation: Jiu-Lin Song, Wei Gao, Yan Zhong, Lu-Nan Yan, Jia-Yin Yang, Tian-Fu Wen, Bo Li, Wen-Tao Wang, Hong Wu, Ming-Qing Xu, Zhe-Yu Chen, Yong-Gang Wei, Li Jiang, Jian Yang, Department of Liver Surgery, Liver Transplantation Center, West China Hospital of Sichuan University, Chengdu 610041, Sichuan Province, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Wu
authors.affiliation: Jiu-Lin Song, Wei Gao, Yan Zhong, Lu-Nan Yan, Jia-Yin Yang, Tian-Fu Wen, Bo Li, Wen-Tao Wang, Hong Wu, Ming-Qing Xu, Zhe-Yu Chen, Yong-Gang Wei, Li Jiang, Jian Yang, Department of Liver Surgery, Liver Transplantation Center, West China Hospital of Sichuan University, Chengdu 610041, Sichuan Province, China.
authors.forename: Ming-Qing
authors.initials: MQ
authors.lastname: Xu
authors.affiliation: Jiu-Lin Song, Wei Gao, Yan Zhong, Lu-Nan Yan, Jia-Yin Yang, Tian-Fu Wen, Bo Li, Wen-Tao Wang, Hong Wu, Ming-Qing Xu, Zhe-Yu Chen, Yong-Gang Wei, Li Jiang, Jian Yang, Department of Liver Surgery, Liver Transplantation Center, West China Hospital of Sichuan University, Chengdu 610041, Sichuan Province, China.
authors.forename: Zhe-Yu
authors.initials: ZY
authors.lastname: Chen
authors.affiliation: Jiu-Lin Song, Wei Gao, Yan Zhong, Lu-Nan Yan, Jia-Yin Yang, Tian-Fu Wen, Bo Li, Wen-Tao Wang, Hong Wu, Ming-Qing Xu, Zhe-Yu Chen, Yong-Gang Wei, Li Jiang, Jian Yang, Department of Liver Surgery, Liver Transplantation Center, West China Hospital of Sichuan University, Chengdu 610041, Sichuan Province, China.
authors.forename: Yong-Gang
authors.initials: YG
authors.lastname: Wei
authors.affiliation: Jiu-Lin Song, Wei Gao, Yan Zhong, Lu-Nan Yan, Jia-Yin Yang, Tian-Fu Wen, Bo Li, Wen-Tao Wang, Hong Wu, Ming-Qing Xu, Zhe-Yu Chen, Yong-Gang Wei, Li Jiang, Jian Yang, Department of Liver Surgery, Liver Transplantation Center, West China Hospital of Sichuan University, Chengdu 610041, Sichuan Province, China.
authors.forename: Li
authors.initials: L
authors.lastname: Jiang
authors.affiliation: Jiu-Lin Song, Wei Gao, Yan Zhong, Lu-Nan Yan, Jia-Yin Yang, Tian-Fu Wen, Bo Li, Wen-Tao Wang, Hong Wu, Ming-Qing Xu, Zhe-Yu Chen, Yong-Gang Wei, Li Jiang, Jian Yang, Department of Liver Surgery, Liver Transplantation Center, West China Hospital of Sichuan University, Chengdu 610041, Sichuan Province, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Yang
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D019540:Area Under Curve; D016009:Chi-Square Distribution; D002681:China / Q000453:epidemiology; D003920:Diabetes Mellitus / Q000139:chemically induced / Q000175:diagnosis / Q000453:epidemiology / Q000517:prevention & control*; D016903:Drug Monitoring; D005260:Female; D006084:Graft Rejection / Q000276:immunology / Q000517:prevention & control; D006085:Graft Survival / Q000187:drug effects; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000009:adverse effects*; D015994:Incidence; D053208:Kaplan-Meier Estimate; D016031:Liver Transplantation / Q000009:adverse effects*; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D015995:Prevalence; D016016:Proportional Hazards Models; D012372:ROC Curve; D012189:Retrospective Studies; D012307:Risk Factors; D016559:Tacrolimus / Q000008:administration & dosage / Q000009:adverse effects*; D013997:Time Factors; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D007166:Immunosuppressive Agents; D016559:Tacrolimus
keywords: Allografts failure; Immunosuppressants; Liver transplantation; Minimum tacrolimus; New-onset diabetes mellitus