PD-1 相关暴发性 1 型糖尿病的临床和免疫学特征。
Clinical and immunological characteristics of PD-1 associated fulminant type 1 diabetes mellitus.
机构信息
Department of Metabolism and Endocrinology, Second Xiangya Hospital, Central South University; Ministry of Education, Key Laboratory of Diabetes Immunology (Central South University); National Clinical Research Center for Metabolic Diseases, Changsha 410011, China.
出版信息
Zhong Nan Da Xue Xue Bao Yi Xue Ban. 2023 Jan 28;48(1):49-58. doi: 10.11817/j.issn.1672-7347.2023.220290.
OBJECTIVES
Programmed death 1 (PD-1) associated fulminant type 1 diabetes (PFD) is a rare acute and critical in internal medicine, and its clinical characteristics are still unclear. This study aims to analyze the clinical characteristics of PFD patients to improve clinical diagnosis and treatment.
METHODS
We retrospectively analyzed the clinical data of 10 patients with PFD admitted to the Second Xiangya Hospital of Central South University, combined with the data of 66 patients reported in the relevant literature, analyzed and summarized their clinical and immunological characteristics, and compared the patients with PFD with different islet autoantibody status.
RESULTS
Combined with our hospital and literature data, a total of 76 patients with PFD were reported, with the age of (60.9±12.1) years old, 60.0% male and body mass index of (22.1±5.2) kg/m2. In 76 patients, the most common tumors were lung cancer (43.4%) and melanoma (22.4%). Among PD-1 inhibitors, the most common drugs are nivolumab (37.5%) and pembrolizumab (38.9%). 82.2% of PFD patients developed diabetes ketoacidosis. The median onset time from PD-1 related inhibitor treatment to hyperglycemia was 95 (36.0, 164.5) d, and the median treatment cycle before the onset of diabetes was 6 (2.3, 8.0) cycles. 26% (19/73) of PFD patients had positive islet autoantibodies, and the proportion of ketoacidosis in the positive group was significantly higher than that in the negative group (100.0% vs 75.0%, P<0.05). The onset time and infusion times of diabetes after PD-1 inhibitor treatment in the autoantibody positive group were significantly lower than those in the autoantibody negative group (28.5 d vs 120.0 d; 2 cycles vs 7 cycles, both P<0.001).
CONCLUSIONS
After initiation of tumor immunotherapy, it is necessary to be alert to the occurrence of adverse reactions of PFD, and the onset of PFD with islet autoantibody positive is faster and more serious than that of patients with autoantibodies negative. Detection of islet autoantibodies and blood glucose before and after treatment with PD-1 inhibitors is of great value for early warning and prediction of PFD.
目的
程序性死亡受体 1（PD-1）相关暴发性 1 型糖尿病（PFD）是一种罕见的内科急症和危重症，其临床特征尚不清楚。本研究旨在分析 PFD 患者的临床特征，以提高临床诊治水平。
方法
我们回顾性分析了中南大学湘雅二医院收治的 10 例 PFD 患者的临床资料，并结合相关文献报道的 66 例患者的数据，分析总结其临床和免疫学特征，并比较了 PFD 患者与不同胰岛自身抗体状态的差异。
结果
结合我院和文献资料，共报道 76 例 PFD 患者，年龄（60.9±12.1）岁，男性占 60.0%，体重指数为（22.1±5.2）kg/m2。76 例患者中最常见的肿瘤为肺癌（43.4%）和黑色素瘤（22.4%）。PD-1 抑制剂中最常见的药物为纳武利尤单抗（37.5%）和帕博利珠单抗（38.9%）。82.2%的 PFD 患者发生糖尿病酮症酸中毒。从 PD-1 相关抑制剂治疗到高血糖的中位发病时间为 95（36.0，164.5）d，发病前的中位治疗周期数为 6（2.3，8.0）个周期。26%（19/73）的 PFD 患者胰岛自身抗体阳性，阳性组酮症酸中毒的比例明显高于阴性组（100.0%比 75.0%，P<0.05）。阳性组糖尿病在 PD-1 抑制剂治疗后的发病时间和输注次数均明显低于阴性组（28.5 d 比 120.0 d；2 个周期比 7 个周期，均 P<0.001）。
结论
启动肿瘤免疫治疗后，需警惕 PFD 不良事件的发生，且伴有胰岛自身抗体阳性的 PFD 发病更快、更严重。检测 PD-1 抑制剂治疗前后的胰岛自身抗体和血糖对 PFD 的早期预警和预测具有重要价值。
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