他克莫司致器官移植后新发糖尿病的发病机制研究进展

器官移植术后新发糖尿病是实体器官移植后的主要并发症之一,免疫抑制常被认为是导致器官移植术后新发糖尿病的主要因素,包括糖皮质激素、钙调磷酸酶抑制剂等。其中,钙调磷酸酶抑制剂对血糖的影响最大。他克莫司是从链霉菌属中分离出的发酵产物,是一种强效免疫抑制性大环内酯类抗生素,现广泛用于实体器官移植的免疫抑制剂。他克莫司对细胞免疫有选择性抑制作用,主要通过抑制白细胞介素-2的释放,全面抑制T淋巴细胞的作用。通过查阅文献,从三方面综述了他克莫司引起高血糖的机制,包括影响β细胞存活和复制、影响胰岛素分泌、影响外周组织的胰岛素利用。

A novel clinical model for risk prediction and stratification of new-onset diabetes mellitus after distal pancreatectomy

Background:The incidence of new-onset diabetes mellitus(NODM)after distal pancreatectomy(DP)remains high.Few studies have focused on NODM in patients with pancreatic benign or low-grade malignant lesions(PBLML).This study aimed to develop and validate an effective clinical model for risk prediction and stratification of NODM after DP in patients with PBLML.Methods:A follow-up survey was conducted to investigate NODM in patients without preoperative DM who underwent DP.Four hundred and forty-eight patients from Peking Union Medical College Hospital(PUMCH)and 178 from Guangdong Provincial People’s Hospital(GDPH)met the inclusion criteria.They constituted the training cohort and the validation cohort,respectively.Univariate and multivariate Cox regression,as well as least absolute shrinkage and selection operator(LASSO)analyses,were used to identify the independent risk factors.The nomogram was constructed and verified.Concordance index(C-index),receiver operating characteristic(ROC)curve,calibration curves,and decision curve analysis(DCA)were applied to assess its predictive performance and clinical utility.Accordingly,the optimal cut-off point was determined by maximally selected rank statistics method,and the cumulative risk curves for the high-and low-risk populations were plotted to evaluate the discrimination ability of the nomogram.Results:The median follow-up duration was 42.8 months in the PUMCH cohort and 42.9 months in the GDPH cohort.The postoperative cumulative 5-year incidences of DM were 29.1%and 22.1%,respectively.Age,body mass index(BMI),length of pancreatic resection,intraoperative blood loss,and concomitant splenectomy were significant risk factors.The nomogram demonstrated significant predictive utility for post-pancreatectomy DM.The C-indexes of the nomogram were 0.739 and 0.719 in the training and validation cohorts,respectively.ROC curves demonstrated the predictive accuracy of the nomogram,and the calibration curves revealed that prediction results were in general agreement with the actual results.The considerable clinical applicability of the nomogram was certified by DCA.The optimal cut-off point for Background:The incidence of new-onset diabetes mellitus(NODM)after distal pancreatectomy(DP)remains high.Few studies have focused on NODM in patients with pancreatic benign or low-grade malignant lesions(PBLML).This study aimed to develop and validate an effective clinical model for risk prediction and stratification of NODM after DP in patients with PBLML.Methods:A follow-up survey was conducted to investigate NODM in patients without preoperative DM who underwent DP.Four hundred and forty-eight patients from Peking Union Medical College Hospital(PUMCH)and 178 from Guangdong Provincial People’s Hospital(GDPH)met the inclusion criteria.They constituted the training cohort and the validation cohort,respectively.Univariate and multivariate Cox regression,as well as least absolute shrinkage and selection operator(LASSO)analyses,were used to identify the independent risk factors.The nomogram was constructed and verified.Concordance index(C-index),receiver operating characteristic(ROC)curve,calibration curves,and decision curve analysis(DCA)were applied to assess its predictive performance and clinical utility.Accordingly,the optimal cut-off point was determined by maximally selected rank statistics method,and the cumulative risk curves for the high-and low-risk populations were plotted to evaluate the discrimination ability of the nomogram.Results:The median follow-up duration was 42.8 months in the PUMCH cohort and 42.9 months in the GDPH cohort.The postoperative cumulative 5-year incidences of DM were 29.1%and 22.1%,respectively.Age,body mass index(BMI),length of pancreatic resection,intraoperative blood loss,and concomitant splenectomy were significant risk factors.The nomogram demonstrated significant predictive utility for post-pancreatectomy DM.The C-indexes of the nomogram were 0.739 and 0.719 in the training and validation cohorts,respectively.ROC curves demonstrated the predictive accuracy of the nomogram,and the calibration curves revealed that prediction results were in general agreement with the actual results.The considerable clinical applicability of the nomogram was certified by DCA.The optimal cut-off point for risk prediction value was 2.88, and the cumulative risk curves of each cohort showed significant differences between the high- and low-risk groups. Conclusions: The nomogram could predict and identify the NODM risk population, and provide guidance to physicians in monitoring and controlling blood glucose levels in PBLML patients after DP.