Endocrine Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY.
Weill Cornell Medical College, New York, NY.
Diabetes Care. 2020 Dec;43(12):3106-3109. doi: 10.2337/dc20-0609. Epub 2020 Oct 13.
To characterize immune checkpoint inhibitor-associated diabetes mellitus (ICI-DM) in a single-institution case series.
Retrospective chart review of 18 patients with new-onset ICI-DM following anti-programmed cell death protein 1 (PD-1)/anti-programmed cell death protein ligand 1 (PD-L1) therapy for advanced carcinomas.
Of 18 patients, 9 had diabetic ketoacidosis (median glucose 27.92 mmol/L; median glucose before presentation 6.35 mmol/L). Median C-peptide at ICI-DM diagnosis was low, and it declined during follow-up. Median anti-PD-1/anti-PD-L1 duration before ICI-DM was 3.65 months (range 0.56-12.23 months). Time to ICI-DM onset was a median 1.4 months/3 ICI cycles and 6 months/10 cycles in those patients who were positive and negative for GAD65 autoantibodies, respectively. Time to ICI-DM onset was a median 2.5 months/3 ICI cycles and 4.8 months/8 cycles after anti-PD-L1 or anti-PD-1 therapy, respectively. Significant pancreatic atrophy was seen radiographically.
ICI-DM presents abruptly, appears irreversible, is characterized by pancreatic atrophy, and may occur both earlier following PD-L1 blockade compared with PD-1 inhibition and in those who have positive GAD65 autoantibodies.
在单机构病例系列中描述免疫检查点抑制剂相关的糖尿病(ICI-DM)。
对 18 例接受抗程序性细胞死亡蛋白 1(PD-1)/抗程序性细胞死亡蛋白配体 1(PD-L1)治疗晚期癌后新发 ICI-DM 的患者进行回顾性病历审查。
在 18 例患者中,有 9 例发生糖尿病酮症酸中毒(中位数血糖 27.92mmol/L;中位数就诊前血糖 6.35mmol/L)。ICI-DM 诊断时的中位 C 肽较低,且在随访期间下降。ICI-DM 前中位抗 PD-1/抗 PD-L1 治疗时间为 3.65 个月(范围 0.56-12.23 个月)。在 GAD65 自身抗体阳性和阴性的患者中,ICI-DM 发病的时间中位数分别为 1.4 个月/3 ICI 周期和 6 个月/10 周期。ICI-DM 发病时间中位数分别为抗 PD-L1 或抗 PD-1 治疗后 2.5 个月/3 ICI 周期和 4.8 个月/8 周期。影像学可见明显的胰腺萎缩。
ICI-DM 突然发作,似乎不可逆转,表现为胰腺萎缩,与 PD-1 抑制相比,PD-L1 阻断后可能更早发生,且 GAD65 自身抗体阳性者也可能更早发生。