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Title: Clinical and immunological characteristics of PD-1 associated fulminant type 1 diabetes mellitus.
Author: Qiu J, Luo S, Yin W, Li X, Zhou Z.
Journal: Zhong Nan Da Xue Xue Bao Yi Xue Ban; 2023 Jan 28; 48(1):49-58. PubMed ID: 36935177.
Abstract:
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(programmed death-1，PD-1)相关性暴发性1型糖尿病(PD-1 associated fulminant type 1 diabetes，PFD)是少见的内科急危重症，临床特点尚不清楚。本研究分析PFD患者的临床特点，以期提升临床诊疗水平。方法: 回顾性分析中南大学湘雅二医院(以下简称我院)就诊的10例PFD患者的临床资料，结合相关文献报道的66例患者资料，分析总结其临床与免疫特征，并对不同胰岛自身抗体状态的PFD患者进行比较。结果: 结合我院及文献检索数据，共报道76例PFD患者，年龄(60.9±12.1)岁，男性占60.0%，体重指数(22.1±5.2) kg/m²。76例患者中最常见的肿瘤是肺癌(43.4%)和黑色素瘤(22.4%)。PD-1相关抑制剂最常见的药物是纳武单抗(37.5%)和派姆单抗(38.9%)。82.2%的PFD患者出现糖尿病酮症酸中毒。从PD-1相关抑制剂治疗开始到血糖升高的中位发病时间为95(36.0，164.5) d，糖尿病发病前中位治疗周期为6(2.3，8.0)。26.0%(19/73)的PFD患者胰岛自身抗体阳性，阳性组的酮症酸中毒比例显著高于阴性组(100.0% vs 75.0%，P<0.05)。PD-1抑制剂治疗后的糖尿病发病时间和输注次数在抗体阳性组中均显著低于抗体阴性组(28.5 d vs 120.0 d；2周期vs 7周期，均P<0.001)。结论: 启动肿瘤免疫治疗后需警惕发生PFD不良反应，胰岛自身抗体阳性PFD比阴性患者发病更快、更严重。PD-1相关抑制剂治疗前后检测胰岛自身抗体及血糖对PFD预警预测有重要价值。. OBJECTIVE: 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). CONCLUSION: 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.

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