Peretz David, Faisal Nabiha, Uhanova Julia, Schacter Isanne, McAlpine Diane, Knowles Cori, Minuk Gerald Y
Section of Hepatology.
Section of Endocrinology and Metabolism, Department of Internal Medicine, College of Medicine, University of Manitoba, Winnipeg, Manitoba, Canada.
Can Liver J. 2023 Oct 30;6(3):353-357. doi: 10.3138/canlivj-2022-0046. eCollection 2023 Oct.
Post liver transplant diabetes mellitus (PLTDM) occurs in 10-40% of liver transplant recipients and is associated with increased morbidity and mortality. An important cause of PLTDM is tacrolimus induced, concentration-dependent, inhibition of insulin secretion.
To determine if a newly licenced formulation of tacrolimus (Envarsus-PA), which achieves peak tacrolimus concentrations 20-30% lower than other tacrolimus formulations has less of an inhibitory effect on insulin secretion.
Homeostatic model assessment (HOMA) for insulin secretion (HOMA-S) values and c-peptide levels were determined in 19 adult liver transplant recipients while being maintained on immediate- or slow-release tacrolimus formulations and repeated a minimum of 30 days following conversion to Envarsus-PA.
Insulin secretion was unchanged following conversion to Envarsus-PA (HOMA-S pre-conversion: 154 ± 133 vs. 129 ± 75, post-conversion [ = 0.32], and c-peptide levels; 1059 ± 602 and 934 ± 463 respectively, = 0.42). Fasting blood glucose (FBG) and hemoglobin A1c (HbA1c) levels were also unchanged (FBG 5.7 ± 0.8 pre-conversion vs. 5.6 ± 0.7 post-conversion; = 0.36 and HbA1c 4.9±1.2 pre-conversion versus 5.5±0.2 post-conversion, = 0.34).
Envarsus-PA had no significant effect on insulin secretion or glucose homeostasis beyond that associated with other tacrolimus formulations in adult liver transplant recipients.
肝移植后糖尿病（PLTDM）发生于10% - 40%的肝移植受者中，与发病率和死亡率增加相关。PLTDM的一个重要原因是他克莫司诱导的、浓度依赖性的胰岛素分泌抑制。
确定一种新获批的他克莫司制剂（Envarsus - PA），其他克莫司峰值浓度比其他他克莫司制剂低20% - 30%，是否对胰岛素分泌的抑制作用更小。
对19名成年肝移植受者进行胰岛素分泌的稳态模型评估（HOMA）（HOMA - S）值和C肽水平测定，这些受者维持使用速释或缓释他克莫司制剂，并在转换为Envarsus - PA后至少30天重复测定。
转换为Envarsus - PA后胰岛素分泌未发生变化（转换前HOMA - S：154±133 vs.转换后129±75，P = 0.32），C肽水平分别为1059±602和934±463，P = 0.42）。空腹血糖（FBG）和糖化血红蛋白（HbA1c）水平也未发生变化（转换前FBG 5.7±0.8 vs.转换后5.6±0.7；P = 0.36，转换前HbA1c 4.9±1.2与转换后5.5±0.2，P = 0.34）。
在成年肝移植受者中，与其他他克莫司制剂相比，Envarsus - PA对胰岛素分泌或葡萄糖稳态无显著影响。
