Effects of Late Conversion from Twice-Daily to Once-Daily Slow Release Tacrolimus on the Insulin Resistance Indexes in Kidney Transplant Patients

Valeria Cademartori,Emanuele L Parodi,Giacomo Garibotto,Iris Fontana,Francesca Viazzi,Ernesto Paoletti,Fabio Massarino,Rodolfo Russo,Pasquale Esposito,Antonella Sofia

doi:10.3390/transplantology2010005

Valeria Cademartori, Emanuele L Parodi + Show 8 more

Open Access

https://doi.org/10.3390/transplantology2010005

Copy DOI

Abstract

The use of tacrolimus (Tac) may be involved in the development of new-onset diabetes after transplantation (NODAT) in a dose-related manner. This study aimed to evaluate the effects of a standard twice-daily formulation of Tac (TacBID) vs. the once-daily slow-release formulation (TacOD) on the basal insulin resistance indexes (Homa and McAuley), and related metabolic parameters, in a cohort of kidney transplant patients. We retrospectively evaluated 20 stable renal transplant recipients who were switched from TacBID to TacOD. Blood levels of Tac were analyzed at one-month intervals from 6 months before to 8 months after conversion. Moreover, Homa and McAuley indexes, C-peptide, insulin, HbA1c, uric acid, triglycerides, low-density lipoprotein (LDL) and high-density lipoprotein (HDL)-cholesterol serum levels and their associations with Tac levels were evaluated. We observed a significant decrease in Tac exposure (8.5 ± 2 ng/mL, CV 0.23 vs. 6.1 ± 1.9 ng/mL, CV 0.31, TacBID vs. TacOD periods, p < 0.001) and no significant changes in Homa (1.42 ± 0.4 vs. 1.8 ± 0.7, p > 0.05) and McAuley indexes (7.12 ± 1 vs. 7.58 ± 1.4, p > 0.05). Similarly, blood levels of glucose, insulin, HbA1c, lipids, and uric acid were unchanged between the two periods, while C-peptide resulted significantly lower after conversion to TacOD. These data suggest that in kidney transplant recipients, reduced Tac exposure has no significant effects on basal insulin sensitivity indexes and metabolic parameters.

Highlights

New-onset diabetes after transplantation (NODAT) is a serious complication of transplantation associated with increased mortality and morbidity, and high rates of cardiovascular disease and infection, which are the leading causes of death in renal transplant recipients. [1]
This study aimed to evaluate the effects of the conversion from TacBID to TacOD on the basal insulin resistance indexes (HOMA and McAuley) and related metabolic parameters in a cohort of kidney transplant patients
We found that late conversion from TacBID to TacOD led to a significant reduction in Tac trough levels, considered as the expression of a lower Tac exposure

Summary

Introduction

New-onset diabetes after transplantation (NODAT) is a serious complication of transplantation associated with increased mortality and morbidity, and high rates of cardiovascular disease and infection, which are the leading causes of death in renal transplant recipients. [1]. New-onset diabetes after transplantation (NODAT) is a serious complication of transplantation associated with increased mortality and morbidity, and high rates of cardiovascular disease and infection, which are the leading causes of death in renal transplant recipients. The NODAT incidence varies across different studies, ranging from 0.4%. Incidences between 7%–30% in the first year after transplantation have been reported [2,3]. NODAT recognizes multiple pathogenic mechanisms resulting in an imbalance between insulin production and target tissue insulin demand. This disparity may occur as a result of insulin resistance, increased insulin metabolism, or diminished insulin secretion [4,5].

Objectives

Methods

Conclusion