PD-1抑制剂致1型糖尿病1例及相关病例文献分析.pdfVIP

PD-1抑制剂致1型糖尿病1例及相关病例文献分析 ［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、 霍奇全淋巴瘤、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^ )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。 ［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 PD-1 inhibitor-induced type 1 diabetes mellitus: a case report and literature review LU Lu1，2 ,FENG Ying-nan1，2 ,ZHOU Han3 ,ZENG Yan1，2* (1. Department of Pharmacy, Xuanwu Hospital, Capital Medical University, Beijing 100053 , China； 2. National Research Center for Clinical Medicine of Geriatric Diseases, Beijing 100053,China；3. Department of Clinical Pharmacy,Capital Medical University,Beijing 100069,China) ［Abstract ］ 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 cli­ nicians 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 a­ nalysis. Results Thirty-one patients ,21 males and 10 females, were included in the an