Tacrolimus and PTDM

Q: Tacrolimus has a protective effect against post-transplantation diabetes mellitus (PTDM).

A) True

B) False

Answer: B

Tacrolimus and cyclosporine are calcineurin inhibitors used as standard in post-transplanted patients. Τаϲrolimuѕ is diabetogenic (more than ϲуϲlοѕроrinе). An increased tаϲrоlimսѕ level, particularly above 15 ng/mL, is considered significant enough to cause PTDM within a year of transplantation. Both immediate-release and extended-release versions have the same risk.

The mechanism of action is toxicity to the islet cells, though the effect is reversible. It also directly affects the transcriptional regulation of insսliո expression. Tacrolimus is also suspected to cause severe swelling and vacuolization of islet cells.

#transplantation

#pharmacology

References: 

1. Shah T, Kasravi A, Huang E, et al. Risk factors for development of new-onset diabetes mellitus after kidney transplantation. Transplantation 2006; 82:1673.

2. Rostaing L, Bunnapradist S, Grinyó JM, et al. Novel Once-Daily Extended-Release Tacrolimus Versus Twice-Daily Tacrolimus in De Novo Kidney Transplant Recipients: Two-Year Results of Phase 3, Double-Blind, Randomized Trial. Am J Kidney Dis 2016; 67:648.

3. Dai C, Walker JT, Shostak A, et al. Tacrolimus- and sirolimus-induced human β cell dysfunction is reversible and preventable. JCI Insight 2020; 5.

4. Drachenberg CB, Klassen DK, Weir MR, et al. Islet cell damage associated with tacrolimus and cyclosporine: morphological features in pancreas allograft biopsies and clinical correlation. Transplantation 1999; 68:396.