Battezzati A, Benedini S, Caldara R, Calori G, Secchi A, Pozza G, Luzi L
Amino Acid and Stable Isotopes Laboratory, San Raffaele Scientific Institute, Via Olgettina, 60, 20132 Milano, Italy.
Transplantation. 2001 Jun 15;71(11):1560-5. doi: 10.1097/00007890-200106150-00013.
Strategies to prevent the return to the diabetic state for graft loss or failure or any other cause after pancreas transplantation require the identification of the subjects at risk. This study evaluated whether daily glucose, insulin, and c-peptide profiles and studies of insulin sensitivity and secretion after transplantation predict pancreatic graft failure.
Fifty-three subjects with type 1 diabetes with end-stage renal failure who received a combined pancreas and kidney transplant underwent the following procedures 1 year after transplantation: 1-day metabolic profiles, sampling every 2 hours for plasma glucose, serum insulin, and c-peptide (n=51); an intravenous glucose tolerance test (IVGTT) to evaluate insulin secretion (n=48); and an euglycemic insulin clamp to evaluate insulin sensitivity (M value, n=14). The recipients were then followed up to 8 years (mean follow-up 4.8+/-0.3 years) to evaluate the return to the diabetic state.
Survival analysis showed that plasma glucose in the profiles and insulin secretion in IVGTT were strongly related to the risk of returning to the diabetic state. A cutoff value of mean daily plasma glucose >127 mg/dL, corresponding to the top quartile of the mean plasma glucose distribution in the profiles, predicted the return to the diabetic state within 4 years from transplantation with a 93% specificity and a 100% sensitivity. A cutoff value of insulin delta peak <32 microU/ml in the IVGTT predicted the return to the diabetic state within 4 years from transplantation with a 75% specificity and a 75% sensitivity. In contrast, the M value in the clamp was devoid of predictive value.
This study indicates that the mean 24-h plasma glucose 1 year after transplantation is the strongest predictor of the return to the diabetic state. The risk is related to defects in insulin secretion and not to insulin resistance. Metabolic profiles can be used to screen the subjects at risk to strictly monitor the graft function and to investigate early determinants of graft failure.
胰腺移植后，为防止因移植物丢失、功能衰竭或其他任何原因而恢复至糖尿病状态，需要识别出有风险的受试者。本研究评估了移植后的每日血糖、胰岛素和C肽水平以及胰岛素敏感性和分泌研究是否能预测胰腺移植失败。
53例患有终末期肾衰竭的1型糖尿病患者接受了胰肾联合移植，移植后1年进行了以下检查：1天的代谢指标检测，每2小时采集一次血浆葡萄糖、血清胰岛素和C肽样本（n = 51）；静脉葡萄糖耐量试验（IVGTT）以评估胰岛素分泌（n = 48）；以及正常血糖胰岛素钳夹试验以评估胰岛素敏感性（M值，n = 14）。随后对受者进行长达8年的随访（平均随访4.8±0.3年），以评估是否恢复至糖尿病状态。
生存分析表明，代谢指标检测中的血浆葡萄糖和IVGTT中的胰岛素分泌与恢复至糖尿病状态的风险密切相关。每日平均血浆葡萄糖>127 mg/dL的临界值，对应于代谢指标检测中血浆葡萄糖分布的上四分位数，预测移植后4年内恢复至糖尿病状态的特异性为93%，敏感性为100%。IVGTT中胰岛素δ峰<32 microU/ml的临界值预测移植后4年内恢复至糖尿病状态的特异性为75%，敏感性为75%。相比之下，钳夹试验中的M值没有预测价值。
本研究表明，移植后1年的24小时平均血浆葡萄糖是恢复至糖尿病状态的最强预测指标。风险与胰岛素分泌缺陷有关，而非胰岛素抵抗。代谢指标可用于筛查有风险的受试者，以严格监测移植物功能并研究移植失败的早期决定因素。
