Akdeniz University, School of Medicine, Division of Endocrinology, Antalya, Turkey.
Akdeniz University, School of Medicine, Division of Endocrinology, Antalya, Turkey.
J Natl Med Assoc. 2020 Jun;112(3):250-257. doi: 10.1016/j.jnma.2020.03.012. Epub 2020 Apr 16.
Immunosuppressive drugs used in transplantation patients, may contribute to the development of post-transplant diabetes mellitus through their possible adverse effects on incretins. We aimed to compare the effects of different immunosuppressive drugs used in renal transplantation patients on glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) levels.
Forty five subjects were enrolled in the study (cyclosporine-treated 15 and tacrolimus-treated renal transplant patients 15, and healthy volunteers as a control group 15). Oral glucose tolerance test with 75 gr glucose was performed. GLP-1 and GIP levels were measured at 0 (baseline), 30, 60, 90, 120 min using ELISA method.
A statistically significant level of difference was detected in GLP-1 levels at the baseline, 30th and 120th minutes among all three groups (p < 0,001, p = 0,026 and p = 0,022, respectively). Baseline GLP-1 levels in cyclosporine-treated renal transplant patients were higher than in both tacrolimus-treated renal transplant patients (p = 0,016) and control groups (p < 0,001). GLP-1 levels at the 30th minute were higher in tacrolimus-treated renal transplant patients when compared to the cyclosporine-treated renal transplant patients (p = 0,024). GLP-1 levels at the 120th minute were higher in tacrolimus-treated renal transplant patients than the control group (p = 0,024). The areas under the curve of GLP-1 was higher in tacrolimus-treated renal transplant patients when compared to the control group (p = 0,018). GIP levels at 120th was lower in cyclosporine-treated renal transplant patients when compared to control group (p = 0,003).
These findings showed a temporally affected incretin hormones in renal transplant patients, a preserved GLP-1 response to an oral glucose load in renal transplant patients on cyclosporine and increased GLP -1 response to an oral glucose load in those on tacrolimus.
移植患者中使用的免疫抑制剂可能会通过对肠促胰岛素的潜在不良影响而导致移植后糖尿病的发生。我们旨在比较肾移植患者中使用的不同免疫抑制剂对胰高血糖素样肽-1(GLP-1)和葡萄糖依赖性胰岛素释放肽(GIP)水平的影响。
本研究纳入了 45 名受试者(环孢素治疗的 15 名和他克莫司治疗的肾移植患者 15 名,以及健康志愿者作为对照组 15 名)。口服 75 克葡萄糖进行口服葡萄糖耐量试验。使用 ELISA 法在 0(基线)、30、60、90 和 120 分钟测量 GLP-1 和 GIP 水平。
三组患者的基线、30 分钟和 120 分钟的 GLP-1 水平均存在统计学显著差异(p<0.001、p=0.026 和 p=0.022)。环孢素治疗的肾移植患者的基线 GLP-1 水平高于他克莫司治疗的肾移植患者(p=0.016)和对照组(p<0.001)。与环孢素治疗的肾移植患者相比,他克莫司治疗的肾移植患者的 30 分钟 GLP-1 水平更高(p=0.024)。与对照组相比,他克莫司治疗的肾移植患者的 120 分钟 GLP-1 水平更高(p=0.024)。与对照组相比,他克莫司治疗的肾移植患者的 GLP-1 曲线下面积更高(p=0.018)。与对照组相比,环孢素治疗的肾移植患者的 120 分钟 GIP 水平更低(p=0.003)。
这些发现表明肾移植患者的肠促胰岛素激素存在时间依赖性变化,环孢素治疗的肾移植患者对口服葡萄糖负荷的 GLP-1 反应正常,而他克莫司治疗的肾移植患者对口服葡萄糖负荷的 GLP-1 反应增加。