帕博利珠单抗相关1型糖尿病文献病例分析

Literature case analysis of type 1 diabetes mellitus caused by pembrolizumab

目的探讨帕博利珠单抗相关1型糖尿病(T1DM)的临床特点。方法检索有关数据库(截至2023年8月31日),收集帕博利珠单抗相关T1DM病例报告类文献,提取患者的基本信息,帕博利珠单抗使用情况,联合用药情况,T1DM发生情况、实验室检查结果、临床表现、治疗与转归等,进行描述性统计分析。结果纳入分析的患者共48例(来自46篇文献),男性27例,女性21例;年龄12~85岁,中位年龄64岁;原发疾病主要为肺癌和黑色素瘤。38例患者有用药至诊断T1DM的时间记录,为21~660 d(中位时间84 d)。41例发生糖尿病酮症酸中毒(DKA),10例发生暴发型T1DM;主要临床表现为多尿、多饮、口干,部分患者出现呼吸困难或意识障碍。45例患者有血糖检测记录,血糖水平9.1~69.7 mmol/L,中位血糖水平31.8 mmol/L;43例有糖化血红蛋白检测记录,36例糖化血红蛋白≥6.5%;35例有血清C肽检测记录,30例血清C肽低于参考值下限。诊断为T1DM后,35例停用帕博利珠单抗,2例未停药,无相关记录者11例;46例接受胰岛素治疗,2例无相关记录。48例患者中2例血糖恢复正常,22例血糖控制良好,1例病情恶化,1例肿瘤进展,3例因肿瘤转移死亡,1例因T1DM后甲状腺及垂体功能受损死亡,18例预后未提及。35例停用帕博利珠单抗的患者中11例重启免疫治疗。结论帕博利珠单抗相关T1DM的临床表现与普通T1MD相似,但DKA发生率较高。半数患者经胰岛素治疗后血糖控制良好。

Objective To explore the clinical characteristics of pembrolizumab-related type 1 diabetes mellitus(T1DM).Methods The relevant databases(up to August 31,2023)were searched and the basic information of patients,application of pembrolizumab,combination medication,the occurrence of T1DM,laboratory test results,clinical manifestation,treatment and prognosis were analyzed descriptively and statistically.Results A total of 48 patients(from 46 articles)were included in the analysis,including 27 males and 21 females,aged from 12 to 85 years with a median age of 64 years.The primary diseases were mainly lung cancer and melanoma.Thirty-eight patients had records of time from medication to diagnosis of T1DM,which was 21-660 days(a median time of 84 days).Of the 48 patients,41 developed diabetes ketoacidosis(DKA),and 10 developed fulminant T1DM.The main clinical manifestations were polyuria,polydipsia,and thirst,and some patients had dyspnea or disturbance of consciousness.Forty-five patients had blood glucose testing records,with blood glucose levels ranging from 9.1 to 69.7 mmol/L and a median blood glucose level of 31.8 mmol/L;43 cases had records of glycated hemoglobin testing,of which 36 cases had glycated hemoglobin≥6.5%;35 cases had serum C-peptide detection records,and 30 cases had serum C-peptide below the lower limit of the reference value.After being diagnosed with T1DM,35 patients stopped pembrolizumab,2 cases did not discontinue,and 11 cases had no relevant records;46 patients received insulin therapy and 2 cases had no relevant records.Among the 48 patients,2 patients′blood glucose returned to normal,22 patients′blood glucose was well controlled,1 patient′s condition deteriorated,1 patient′s tumor progressed,4 patients died,and 18 patients′prognosis was not reported.Among 35 patients who stopped using pembrolizumab,11 patients restarted immunotherapy.Conclusions The clinical manifestations of pembrolizumab-related T1DM are similar to those of common T1DM,but the incidence of DKA is higher.Half of the patients′blood glucose can be well controlled after insulin treatment.