Nankivell B J, Chapman J R, Bovington K J, Spicer S T, O'Connell P J, Allen R D
National Pancreas Transplant Unit, Westmead Hospital, Sydney, Australia.
Transplantation. 1996 Jun 27;61(12):1705-11. doi: 10.1097/00007890-199606270-00007.
Although successful simultaneous pancreas and kidney transplantation (SPK) achieves normoglycemia in the majority of diabetic recipients with end-stage renal disease, little is known about the factors that influence long-term endocrine function. In this prospective study of 48 bladder-drained SPK patients, 209 oral glucose tolerance tests were performed between 3 months and 6 years after transplantation. Normal fasting glucose levels and systemic hyperinsulinemia were stable for up to 6 years after SPK. Multivariate analysis revealed that increased area-under-curve (AUC) levels of C-peptide 3 months after transplantation were predicted by short surgical pancreas anastomosis time, greater recipient body weight, and total HLA mismatch score. Episodes of acute pancreas rejection were not associated with reduced allograft insulin output in the long term. Insulin output, stimulated by oral glucose tolerance tests and assessed by the ratio of AUC insulin to AUC glucose, fell gradually after transplantation and was decreased by an elevated serum calcium level and high cyclosporine dose. The ratio of fasting insulin to glucose, which acts as a marker of peripheral insulin resistance, fell with time after transplantation and was increased by greater body weight, higher prednisolone dose, and lower cyclosporine dose. The inhibitory effect of cyclosporine on both fasting and postprandial insulin output was, however, minor when quantified by multivariate analysis. Endocrine function of the transplanted pancreas was not correlated with its exocrine function measured by urinary amylase excretion, nor was there a correlation with change in renal function measured by isotopic glomerular filtration rate. In summary, simultaneous pancreas and kidney transplantation leads to excellent long-term glucose homeostasis maintained at the expense of systemic hyperinsulinemia. The key factors adversely affecting peripheral resistance in SPK were corticosteroid therapy, body weight, and time after transplantation. The susceptibility of islets to ischemia-reperfusion injury, as quantitated by surgical anastomosis time, may have implications for islet transplantation programs, as may the relative resistance of islets to allograft rejection. Glucose homeostasis after SPK, while remaining abnormal, may be used as the standard against which islet transplantation must be measured.
尽管成功的胰肾联合移植（SPK）能使大多数终末期肾病糖尿病受者实现血糖正常，但对于影响长期内分泌功能的因素却知之甚少。在这项对48例膀胱引流式SPK患者的前瞻性研究中，移植后3个月至6年期间共进行了209次口服葡萄糖耐量试验。SPK术后长达6年，空腹血糖水平正常且全身高胰岛素血症保持稳定。多因素分析显示，移植后3个月C肽曲线下面积（AUC）水平升高可由胰腺手术吻合时间短、受者体重增加和HLA错配总分预测。急性胰腺排斥反应发作从长期来看与移植胰腺胰岛素分泌减少无关。口服葡萄糖耐量试验刺激的胰岛素分泌，通过AUC胰岛素与AUC葡萄糖的比值评估，移植后逐渐下降，且血清钙水平升高和环孢素剂量高会使其降低。空腹胰岛素与葡萄糖的比值作为外周胰岛素抵抗的标志物，移植后随时间下降，且体重增加、泼尼松龙剂量高和环孢素剂量低会使其升高。然而，通过多因素分析定量时，环孢素对空腹和餐后胰岛素分泌的抑制作用较小。移植胰腺的内分泌功能与其通过尿淀粉酶排泄测量的外分泌功能无关，也与通过同位素肾小球滤过率测量的肾功能变化无关。总之，胰肾联合移植可实现出色的长期血糖稳态，但代价是全身高胰岛素血症。对SPK外周抵抗产生不利影响的关键因素是皮质类固醇治疗、体重和移植后时间。手术吻合时间所量化的胰岛对缺血再灌注损伤的易感性，可能对胰岛移植项目有影响，胰岛对移植排斥的相对抗性也可能如此。SPK后的血糖稳态虽仍异常，但可作为衡量胰岛移植的标准。
