PD-1抑制剂致1型糖尿病1例及相关病例文献分析  

PD-1 inhibitor-induced type 1 diabetes mellitus:a case report and literature review

作　　者：陆璐[1,2] 冯英楠 周涵 曾艳 LU Lu;FENG Ying-nan;ZHOU Han;ZENG Yan(Department of Pharmacy,Xuanwu Hospital,Capital Medical University,Beijing 100053,China;National Research Center for Clinical Medicine of Geriatric Diseases,Beijing 100053,China;Department of Clinical Pharmacy,Capital Medical University,Beijing 100069,China)

机构地区：[1]首都医科大学宣武医院药学部,北京100053 [2]国家老年疾病临床医学研究中心,北京100053 [3]首都医科大学临床药学系,北京100069

出　　处：《实用药物与临床》2022年第3期255-261,共7页Practical Pharmacy and Clinical Remedies

基　　金：北京市科学委员会项目(D181100000218002)。

摘　　要：目的探讨程序性死亡分子1(PD-1)抑制剂相关糖尿病的临床特点、发病机制、临床处理原则及治疗,提高临床医生对PD-1抑制剂使用的安全意识。方法报道1例PD-1抑制剂致1型糖尿病病例,并检索PubMed、ScienceDirect、万方、中国知网和维普数据库,收集PD-1抑制剂致1型糖尿病的病例,并与本病例进行汇总分析。结果检索到相关病例31例,男21例,女10例;年龄12~80岁,中位年龄61岁;原发肿瘤非小细胞肺癌11例(35.5%),黑色素瘤6例(19.4%),转移性黑色素瘤3例,肺鳞癌、转移性肾细胞癌各2例,肝癌、骨肉瘤、霍奇金淋巴瘤、食管鳞癌、胃癌、小细胞肺癌、心源性血管肉瘤各1例;单独或联合使用纳武普利单抗18例(62%),应用帕博利珠单抗9例(31%),信迪利单抗和特瑞普利单抗各1例,另外2例未报告;发病中位时间为用药后9周(2周,60周);26例(83.9%)患者以糖尿病酮症酸中毒为首发症状,发病时患者空腹血糖平均值为39.6 mmol/L(17.4~77.8 mmol/L);糖化血红蛋白(HbA_(1c))平均值为8.0%(6.1%~17.3%);C肽水平均低于正常或无法测出;28例患者检测了GAD抗体,10例(35.7%)为阳性,其余均为阴性;13例(52%)患者病情稳定后继续PD-1抑制剂治疗,12例(48%)患者终止了PD-1抑制剂治疗,6例在文献中未做描述。6例(19.4%)患者使用PD-1抑制剂后同时出现甲状腺等内分泌免疫相关疾病。结论PD-1抑制剂相关糖尿病常以危及生命的糖尿病酮症酸中毒为首发症状,加强C-肽和胰岛素抗体等预测标志物的检测并及时诊治对患者远期预后至关重要。Objective To investigate the clinical characteristics,pathogenesis,clinical management principles and treatment of diabetes mellitus associated with programmed death molecule 1 inhibitor(PD-1),and to improve clinicians′awareness of the safety of PD-1 inhibitor use.Methods One case of type 1 diabetes caused by PD-1 inhibitor was reported,and PubMed,ScienceDirect,Wanfang,China Knowledge Network and Vipshop databases were searched for the cases of type 1 diabetes caused by PD-1 inhibitor,which were summarized along with this case for statistical analysis.Results Thirty-one patients,21 males and 10 females,were included in the analysis.Age ranged from 12 to 80 years,with a median age of 61 years.The primary tumors were non-small cell lung cancer in 11 cases(35.5%),melanoma in 6 cases(19.4%),metastatic melanoma in 3 cases,squamous lung cancer and metastatic renal cell carcinoma in 2 cases each,and hepatocellular carcinoma,osteosarcoma,Hodgkin′s lymphoma,esophageal squamous carcinoma,gastric cancer,small cell lung cancer,and cardiogenic angiosarcoma in 1 case each.There were 18 cases(62%)using nivolumab alone or in combination,9 cases(31%)using pembrolizumab,1 case using sintilimab and one using toripalimab,and 2 other cases were not reported.The median time to onset was 9 weeks after drug administration(2 w,60 w).Totally 26 patients(83.9%)had diabetic ketoacidosis as the first symptom.The mean fasting glucose of the patients at the onset was 39.6 mmol/L(17.4~77.8 mmol/L).The mean value of glycosylated hemoglobin was 8.0%(6.1%~17.3%).C-peptide levels were below normal or undetectable.A total of 28 patients were tested for GAD antibodies,10(35.7%)patients were positive for GAD antibodies,and the rest were negative;13(52%)patients continued PD-1 inhibitor therapy after stabilization of disease,while 12(48%)patients discontinued PD-1 inhibitor.Six cases were not described in the literature.Six patients(19.4%)also developed endocrine immune-related diseases,such as thyroid,concomitantly with the use of PD-1 inhibitors.

关 键 词：PD-1抑制剂 1型糖尿病 糖尿病酮症酸中毒 特瑞普利单抗 文献分析 

分 类 号：R587.1[医药卫生—内分泌]