韩丽, 余洁, 刘艺文, 付勇, 平凡, 李伟, 张化冰, 许岭翎, 李玉秀. 5例免疫检查点抑制剂相关糖尿病临床特点分析[J]. 罕见病研究, 2023, 2(3): 353-358. DOI: 10.12376/j.issn.2097-0501.2023.03.006
引用本文: 韩丽, 余洁, 刘艺文, 付勇, 平凡, 李伟, 张化冰, 许岭翎, 李玉秀. 5例免疫检查点抑制剂相关糖尿病临床特点分析[J]. 罕见病研究, 2023, 2(3): 353-358. DOI: 10.12376/j.issn.2097-0501.2023.03.006
HAN Li, YU Jie, LIU Yiwen, FU Yong, PING Fan, LI Wei, ZHANG Huabing, XU Lingling, LI Yuxiu. Clinical Characteristics of 5 Cases of Immune Checkpoint Inhibitor Induced Diabetes Mellitus[J]. Journal of Rare Diseases, 2023, 2(3): 353-358. DOI: 10.12376/j.issn.2097-0501.2023.03.006
Citation: HAN Li, YU Jie, LIU Yiwen, FU Yong, PING Fan, LI Wei, ZHANG Huabing, XU Lingling, LI Yuxiu. Clinical Characteristics of 5 Cases of Immune Checkpoint Inhibitor Induced Diabetes Mellitus[J]. Journal of Rare Diseases, 2023, 2(3): 353-358. DOI: 10.12376/j.issn.2097-0501.2023.03.006

5例免疫检查点抑制剂相关糖尿病临床特点分析

Clinical Characteristics of 5 Cases of Immune Checkpoint Inhibitor Induced Diabetes Mellitus

  • 摘要:
      目的  总结分析5例免疫检查点抑制剂相关糖尿病(ICI-DM)患者临床特点及治疗随访结局,并复习相关文献,以期为临床医生诊治该病提供参考。
      方法  回顾性分析2018年12月至2023年2月于北京协和医院就诊的5例ICI-DM患者的临床资料。
      结果  5例患者平均年龄(65±7)岁,均使用程序性细胞死亡受体1(PD-1)或其配体抑制剂(PD-L1)治疗。5例患者从第1次免疫治疗到发现血糖升高的中位时间为100(43,210)d,接受免疫治疗的中位周期为7(2.5,10.5)周期。5例患者均以糖尿病酮症或酮症酸中毒起病。起病时尿酮体阳性,随机血糖为(36.36±15.89)mmol/L,糖化血红蛋白(8.6%±0.66%),动脉血pH值(7.28±0.16),中位空腹C肽水平为0.09(0.05,0.32)μg/L。5例患者起病血糖水平3或4级,均暂停ICI治疗,启动胰岛素治疗,胰岛素日治疗用量(56±20)IU,并辅以降糖药物治疗。治疗后尿酮体转阴,pH值升至正常范围,随机血糖明显下降(治疗前后随机血糖差值中位数为21.30 mmol/L,P=0.043),治疗有效。随访患者均继续使用胰岛素,血糖稳定后重启PD-1或PD-L1抑制剂治疗,肿瘤病情控制稳定。
      结论  ICI-DM主要发生于PD-1或PD-L1抑制剂治疗后,多以急性高血糖起病,实验室检查提示胰岛素分泌缺陷,部分患者伴胰岛细胞抗体、谷氨酸脱羧酶抗体、自身抗体阳性,需要早期诊断并持续接受胰岛素治疗,内分泌科予以控制血糖后可重启ICI治疗。

     

    Abstract:
      Objective  By summarizing the clinical characteristics and follow-up outcomes of 5 patients with immune checkpoint inhibitor induced diabetes mellitus (ICI-DM) and reviewing the relevant literatures, the article aims at providing reference to clinicians in the diagnosis and treatment of the ICI-DM.
      Methods  Clinical data of 5 patients with ICI-DM who were admitted to Peking Union Medical College Hospital from December 2018 to February 2023 and did retrospectively analyzed.
      Results  Five patients with a mean age of (65±7)years received treatment by the programmed cell death 1 (PD-1) or its ligand inhibitor (PD-L1). The median time from the first immunotherapy to the discovery of elevated plasma glucose was 100 (43, 210)days, and the median cycle of immunotherapy was 7 (2.5, 10.5). The onset of the illness of all the 5 patients started with diabetic ketosis or ketoacidosis. At the onset, urine ketone bodies were positive, random plasma glucose was (36.36±15.89)mmol/L, glycosylated hemoglobin A1c (HbA1c)was (8.6%±0.66%), arterial blood pH was (7.28±0.16), and the median fasting C-peptide level was 0.09 (0.05, 0.32)μg/L. Five patients had an onset plasma glucose level of grade 3 or 4.Then, ICI treatment was discontinued in all patients and insulin therapy started. The daily dosage of insulin was (56±20)IU, supplemented with hypoglycemic drugs. After treatment, urine ketone body turned negative, pH value increased to normal range, and random plasma glucose decreased significantly (the median difference of random blood glucose before and after treatment was 21.30 mmol/L, P=0.043) showing that the treatment was effective. During the follow-up, all patients continued to use insulin. The PD-1 or PD-L1 inhibitors were restarted after hyperglycemia remission. The tumor condition was under control.
      Conclusions  ICI-DM mainly occurs in patients who receive treatment with PD-1 or PD-L1 inhibitors usually with acute hyperglycemia whose laboratory tests indicate insulin secretion defects. Some patients had positive islet cell antibodies, glutamic acid decarboxylase antibodies and autoantibodies.Patients with positive autoantibodies needed early diagnosis and continuous insulin treatment. ICI treatment can be restarted after endocrinologists brought the blood glucose under control.

     

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