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The Impact of Preexisting and Post-transplant Diabetes Mellitus on Outcomes Following Liver Transplantation

Aravinthan, Aloysious D. PhD1,2,3; Fateen, Waleed PhD2,3; Doyle, Adam C. MBBS, BMedSci, FRACP1,4; Venkatachalapathy, Suresh V. MBBS, MRCP3; Issachar, Assaf MD1,5; Galvin, Zita MBBS, MD1; Sapisochin, Gonzalo MD1; Cattral, Mark S. MSc, MD, FRCSC1; Ghanekar, Anand MD, PhD, FRCSC1; McGilvray, Ian D. MD, PhD, FRCSC1; Selzner, Markus MD1; Grant, David R. MD, FRCSC1; Selzner, Nazia MD, PhD1; Lilly, Leslie B. MSc, MD, FRCPC1; Renner, Eberhard L. MD, FRCPC, FAASLD1,6; Bhat, Mamatha MD, MSc, FRCPC1

doi: 10.1097/TP.0000000000002757
Original Clinical Science—Liver

Background. Diabetes mellitus (DM) is said to adversely affect transplant outcomes. The aim of this study was to investigate the impact of pre-existing and new-onset DM on liver transplantation (LT) recipients.

Methods. A single-center retrospective analysis of prospectively collected data of LT recipients (1990–2015) was undertaken.

Results. Of the 2209 patients, 13% (n = 298) had Pre-DM, 16% (n = 362) developed post-transplant diabetes mellitus (PTDM), 5% (n = 118) developed transient hyperglycemia (t-HG) post-LT, and 65% (n = 1431) never developed DM (no DM). Baseline clinical characteristics of patients with PTDM were similar to that of patients with Pre-DM. Incidence of PTDM peaked during the first year (87%) and plateaued thereafter. On multivariate analysis (Bonferroni-corrected), nonalcoholic fatty liver disease and the use of tacrolimus and sirolimus were independently associated with PTDM development. Both Pre-DM and PTDM patients had satisfactory and comparable glycemic control throughout the follow-up period. Those who developed t-HG seem to have a unique characteristic compared with others. Overall, 9%, 5%, and 8% of patients developed end-stage renal disease (ESRD), major cardiovascular event (mCVE), and de novo cancer, respectively. Both Pre-DM and PTDM did not adversely affect patient survival, retransplantation, or de novo cancer. The risks of ESRD and mCVE were significantly higher in patients with Pre-DM followed by PTDM and no DM.

Conclusions. In this largest nonregistry study, patients with Pre-DM and PTDM share similar baseline clinical characteristics. Pre-DM increases the risk of ESRD and mCVE; however, patient survival was comparable to those with PTDM and without diabetes. Understanding the impact of PTDM would need prolonged follow-up.

1 Multiorgan Transplant Program, Toronto General Hospital, University of Toronto, Toronto, ON, Canada.

2 Nottingham Digestive Diseases Centre, School of Medicine, University of Nottingham, Nottingham, United Kingdom.

3 National Institute for Health Research (NIHR) Nottingham Biomedical Research Centre, Nottingham University Hospitals NHS Trust and University of Nottingham, Nottingham, United Kingdom.

4 Department of Gastroenterology and Hepatology, Royal Perth Hospital, Perth, Australia.

5 Liver Institute, Rabin Medical Center, Beilinson Hospital, Petah Tikva, Israel.

6 Department of Medicine, Max Rady College of Medicine/Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, MB, Canada.

Received 14 September 2018. Revision received 6 March 2019.

Accepted 27 March 2019.

The authors declare no funding or conflicts of interest.

A.D.A. designed the study, collected and analyzed the data, and wrote the article. W.F. analyzed data and contributed to the writing of the article. A.C.D. collected and analyzed the data and contributed to the writing of the article. S.V.V. analyzed the data. A.I., Z.G., G.S., M.S.C., A.G., I.D.M., M.S., D.R.G., N.S., L.B.L., and E.L.R. contributed to collection of data. M.B. designed the research study, contributed to the writing of the article, and overall supervision.

Supplemental digital content (SDC) is available for this article. Direct URL citations appear in the printed text, and links to the digital files are provided in the HTML text of this article on the journal’s Web site (

Correspondence: Dr. Mamatha Bhat, Multi Organ Transplant Program, University Health Network/University of Toronto, Toronto, Canada. (

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