New-Onset Diabetes Mellitus (NODM) After Liver Transplantation (LT): The Ultimate Non-diabetogenic Immunosuppressive Therapy

Abstract

New-onset diabetes mellitus (NODM) is a common long-term complication after liver transplantation (LT). It is thought to be drug-induced in most cases, no matter the underlying disease that cause liver failure and indicated transplantation. Standard post-transplantation (PT) immunosuppressive regimens include prolonged use of calcineurin inhibitors (CNIs), namely tacrolimus (TAC), alongside corticosteroids to avoid acute and chronic graft rejection. This combination is well known for its diabetogenicity. Significant differences between the applied regimens stand out concerning the duration and dosages to prevent the metabolic side effects of these drugs in the long run without compromising the graft's survival. Studies were collected after an extensive research of PubMed database for this very specific topic using the following MeSH keywords in multiple combinations: "Liver Transplantation," "Diabetes Mellitus," "NODM," "Tacrolimus," "Cyclosporine A," and "Steroids." In addition, we used the same keywords for regular searches in Google Scholar. Only the relevant English human studies between 2010 and 2020 were collected except for review articles. Duplicates were eliminated using Mendeley software. Twelve relevant studies directly related to the targeted topic were collected and discussed, including five retrospective cohorts, four prospective cohorts, one clinical trial, one prospective pilot, and one case report. Their topics included primarily the factors increasing the risk of new-onset diabetes mellitus after liver transplantation (NODALT), TAC-based immunosuppression and its relative blood levels affecting the possible development of NODALT, the role of cyclosporine in substituting TAC regimen, and the effect of different steroids-avoiding protocols on the prevention of NODALT. The reviewed studies suggested that lowering the serum concentration of tacrolimus (cTAC) throughout the PT period and eliminating the corticosteroids regimen as early as possible, among other measures, can significantly impact the rate of emergence of NODM. This traditional review tackles the most recent studies about NODALT to establish a comprehensive view on this issue and guide clinicians and researchers for the safest immunosuppressive regimen to date, while maintaining a balanced metabolic profile.