4例免疫检查点抑制剂相关糖尿病的病例系列报告并文献分析  

A series report of four cases of immune checkpoint inhibitor-induced diabetes mellitus and literature review

作　　者：杨丹丹 黄红兵[1] 李金兰 刘韬[1] 陈卓佳[1] 潘莹[1] YANG Dandan;HUANG Hongbing;LI Jinan;LIU Tao;CHEN Zhuojia;PAN Ying(Department of Pharmacy,Sun Yat-sen University Cancer Center/State Key Laboratory of Oncology in South China,Guangzhou,510060,Guangdong,China;School of Pharmaceutical Science,Sun Yat-sen University,Guangzhou,510006,Guangdong,China;Department of Pharmacy,Hunan Cancer Hospital,Changsha,410013,Hunan,China)

机构地区：[1]中山大学肿瘤防治中心药学部/华南肿瘤学国家重点实验室,广东广州510060 [2]中山大学药学院,广东广州510006 [3]湖南省肿瘤医院药学部,湖南长沙410013

出　　处：《肿瘤药学》2023年第5期637-643,共7页Anti-Tumor Pharmacy

基　　金：国家抗肿瘤药物临床应用监测网肿瘤规范化诊疗中青年研究基金项目(DSS-YSF2022-06)。

摘　　要：目的探讨免疫检查点抑制剂相关糖尿病的临床特点、不良反应管理以及免疫治疗再挑战。方法报告4例免疫治疗期间新发糖尿病的诊疗过程,并检索PubMed、Web of Science、知网、维普、万方数据库,收集免疫检查点抑制剂治疗相关糖尿病的病例报告,与本院病例进行合并汇总。结果共纳入187例病例,其中71.7%的患者接受PD-1抑制剂治疗,免疫检查点抑制剂相关糖尿病的中位发生时间为用药后14周,胰腺自身抗体阳性患者诊断出糖尿病的时间显著提前[(4.10±33.7)周vs.(22.86±19.16 周,P=0.032)]。75.4%的患者以糖尿病酮症酸中毒为首发症状,65.8%的患者因急诊入院确诊,34.3%的患者同时伴随其它免疫相关内分泌不良反应。66.8%的患者经胰岛素替代治疗后血糖可控,36.9%的患者在血糖控制的条件下重启了免疫治疗。结论免疫检查点抑制剂相关糖尿病具有起病隐匿、并发酮症酸中毒概率高的特点,建议用药期间定期监测血糖,并在出现高血糖时及时进行内分泌检查。Objective To investigate the characteristics,management and immunotherapy rechallenges of immune checkpoint inhibitor-induced diabetes mellitus(ICI-DM).Methods We reported four cases of patients with new-onset DM during ICI treatment,and provide a systematic review of all published cases(PubMed/Web of Science/CNKI/VIP/Wanfang databases)of autoimmune diabetes mellitus related to ICI therapy.The four cases in our hospital were pooled with cases previously reported in the literature.Results A total of 187 cases were included,of which 71.7%were treated with pro-grammed death-1(PD-1)inhibitors,and the ICI-DM occurred with a median time of 14 weeks after the medication.The presence of pancreatic autoantibodies was associated with a shorter time to the onset of DM[(4.10±33.7)vs.(22.86±19.16weeks,P=0.032)].Diabetic ketoacidosis(DKA)was the first symptom in 75.4%of the ICI-DM patients.65.8%of the ICI-DM patients were diagnosed due to emergency admission,and 34.3%were accompanied with other immune-related endo-crine adverse reactions.Glycemic index was controllable in 66.8%patients after insulin replacement therapy,and 36.9%of the patients restarted immunotherapy.Conclusion ICI-DM has the characteristics of insidious onset and high probability of ketoacidosis.Regular monitoring of blood glucose and timely endocrine examination in case of hyperglycemia is recom-mended.

关 键 词：免疫检查点抑制剂 不良反应 糖尿病 酮症酸中毒 病例报告 

分 类 号：R979.1[医药卫生—药品] R587.1[医药卫生—药学]