Wagner K, Webber S A, Kurland G, Boyle G J, Miller S A, Cipriani L, Griffith B P, Fricker F J
Division of Cardiology, Children's Hospital of Pittsburgh, Pa. 15213, USA.
J Heart Lung Transplant. 1997 Mar;16(3):275-82.
Tacrolimus has a negative effect on the pancreatic beta islet cell, and both glucose intolerance and diabetes mellitus are well-recognized complications of tacrolimus-based immunosuppression among adult solid organ transplant recipients.
To determine the association between tacrolimus and new-onset diabetes mellitus in childhood, we reviewed data on 78 pediatric heart and heart-lung/lung recipients receiving tacrolimus-based immunosuppression. Trough tacrolimus levels, fasting and random blood glucose levels, and corticosteroid requirements were reviewed. Diabetes was defined as glucose intolerance requiring long-term insulin treatment more than 30 days after transplantation.
No patient had diabetes before introduction of tacrolimus. In heart-lung/lung recipients, 12 of 28 (43%) had development of diabetes at a median follow-up of 7 months (range 1 to 39). In this group diabetes developed in three of eight (38%) patients with cystic fibrosis and nine of 20 (45%) without (p = NS). In contrast, only two of 50 (4%) heart transplant recipients had development of diabetes. Of the 14 patients with diabetes, 10 had development of diabetes during augmentation of immunosuppression with pulsed corticosteroids. Tacrolimus trough levels were significantly lower in heart compared with heart-lung/lung transplant recipients (9.4 +/- 3.3 versus 15.3 +/- 0.9 ng/ml) (p < 0.01), and at latest follow-up significantly fewer heart transplant recipients were treated with maintenance corticosteroids (28% versus 75%; p < 0.01). In the heart-lung/lung group, no significant difference in tacrolimus levels was found between patients with and without diabetes, nor was there a significant difference in the average corticosteroid dose or number of pulses of corticosteroids per patient.
New-onset diabetes mellitus is rare in pediatric heart transplant recipients receiving tacrolimus-based immunosuppression, but it occurs with a high incidence after pediatric heart-lung/lung transplantation and usually develops during pulsed corticosteroid therapy. However, it is currently not possible to predict which heart-lung/ lung transplant recipients will have development of this serious complication.
他克莫司对胰腺β胰岛细胞有负面影响，葡萄糖耐量异常和糖尿病是成年实体器官移植受者中基于他克莫司的免疫抑制的公认并发症。
为了确定他克莫司与儿童新发糖尿病之间的关联，我们回顾了78例接受基于他克莫司免疫抑制的小儿心脏及心肺/肺移植受者的数据。回顾了他克莫司谷浓度、空腹和随机血糖水平以及皮质类固醇的使用情况。糖尿病定义为移植后30天以上需要长期胰岛素治疗的葡萄糖耐量异常。
在开始使用他克莫司之前，没有患者患有糖尿病。在心肺/肺移植受者中，28例中有12例（43%）在中位随访7个月（范围1至39个月）时发生糖尿病。在该组中，8例囊性纤维化患者中有3例（38%）发生糖尿病，20例非囊性纤维化患者中有9例（45%）发生糖尿病（p=无显著性差异）。相比之下，50例心脏移植受者中只有2例（4%）发生糖尿病。在14例糖尿病患者中，10例在使用脉冲皮质类固醇增强免疫抑制期间发生糖尿病。与心肺/肺移植受者相比，心脏移植受者的他克莫司谷浓度显著更低（9.4±3.3对15.3±0.9 ng/ml）（p<0.01），并且在最近一次随访时，接受维持性皮质类固醇治疗的心脏移植受者显著更少（28%对75%；p<0.01）。在心肺/肺移植组中，糖尿病患者和非糖尿病患者的他克莫司水平没有显著差异，每位患者的平均皮质类固醇剂量或皮质类固醇脉冲次数也没有显著差异。
接受基于他克莫司免疫抑制的小儿心脏移植受者中，新发糖尿病很少见，但在小儿心肺/肺移植后发生率很高，且通常在脉冲皮质类固醇治疗期间发生。然而，目前尚无法预测哪些心肺/肺移植受者会发生这种严重并发症。
