抗PD-1/PD-L1相关糖尿病临床特征  

Clinical Characteristics of Anti-PD-1/PD-L1 Associated with Diabetes

作　　者：王天天 马晓君[1] 缪康琪 张云飞[1] 胡艳美 WANG Tiantian;MA Xiaojun;MIU Kangqi;ZHANG Yunfei;HU Yanmei(Department of Endocrinology and Metabolism,the First Affiliated Hospital of Zhengzhou University,Zhengzhou 450052,China)

机构地区：[1]郑州大学第一附属医院内分泌科,河南郑州450052

出　　处：《河南医学研究》2022年第16期2885-2889,共5页Henan Medical Research

基　　金：河南省高等学校重点科研项目(20A320034);2020年医学科技攻关(重点)项目(SBGJ202002069)。

摘　　要：目的将接受抗程序性死亡蛋白1(PD-1)及程序性死亡蛋白配体1(PD-L1)免疫治疗后发生1型糖尿病(T1DM),即免疫检查点抑制剂诱导的1型糖尿病(ICIT1D)与T1DM及接受抗PD-1/PD-L1治疗后未发生ICIT1D患者的临床资料进行比较,分析抗PD-1/PD-L1相关糖尿病的临床特征。方法选取郑州大学第一附属医院2019年1月至2022年1月收治的应用PD-1/PD-L1抑制剂后出现T1DM的14例实体肿瘤患者,以患者年龄、性别进行1∶3配比,选取接受抗PD-1/PD-L1药物治疗后未发生ICIT1D的42例实体肿瘤患者,同时选取同期初诊T1DM的106例患者,收集临床资料并进行分析。结果14例ICIT1D患者年龄为(55.07±9.75)岁,从第1次应用PD-1/PD-L1抑制剂到诊断T1DM的时间间隔为(242.64±124.47)d。与经典TIDM相比,ICIT1D患者糖化血红蛋白水平、空腹C肽水平、胰岛自身抗体阳性率更低(P<0.05),酮症酸中毒(DKA)发生率更高,但差异无统计学意义(P>0.05)。与未发生ICIT1D的患者相比,ICIT1D患者其他内分泌免疫相关不良反应(irAEs)发生率更高(P<0.05)。结论ICIT1D发病年龄晚,病情进展速度快,β细胞破坏迅速,DKA发生率较高,胰岛自身抗体阳性率低,出现ICIT1D的患者发生其他内分泌irAEs的风险更高。Objective The clinical data of immune checkpoint inhibitor-induced type 1 diabetes(ICIT1 D)were compared with those of type 1 diabetes mellitus(T1 DM)and patients without ICIT1 D after anti-programmed cell death protein 1(PD-1)and programmed cell death-ligand 1(PD-L1)treatment,and the clinical characteristics of anti-PD-1/PD-L1 associated with diabetes were analyzed.Methods Fourteen solid tumor patients who developed T1 DM after application of PD-1/PD-L1 inhibitors were selected from the First Affiliated Hospital of Zhengzhou University from January 2019 to January 2022.In addition,42 solid tumor patients without ICIT1 D after anti-PD-1/PD-L1 drug treatment were selected with a ratio of 1∶3 according to the age and gender.Meanwhile,106 newly diagnosed T1 DM patients were selected,and clinical data were collected and compared.Results The age of 14 ICIT1 D patients was(55.07±9.75)years old,the time from the first application of PD-1/PD-L1 inhibitor to the diagnosis of T1 DM was(242.64±124.47)days.Compared with T1 DM patients,glycosylated hemoglobin,fasting C peptide levels and the positive rates of islet autoantibody in ICIT1 D patients were lower(P<0.05).The incidence of diabetic ketoacidosis(DKA)was higher,but the difference was not statistically significant(P>0.05).Compared with patients without ICIT1 D,patients with ICIT1 D had a higher incidence of other endocrine immune-related adverse events(irAEs)(P<0.05).Conclusion ICIT1 D is characterized by late onset,rapid disease progression,rapidβcell destruction,high incidence of DKA and low positive rate of islet autoantibody.Patients with ICIT1 D are more likely to develop other endocrine irAEs.

关 键 词：免疫检查点抑制剂 程序性死亡蛋白1 免疫相关不良反应 1型糖尿病 实体瘤 

分 类 号：R730.6[医药卫生—肿瘤]