Department of Metabolism and Endocrinology, Key Laboratory of Diabetes Immunology (Central South University), Ministry of Education, National Clinical Research Center for Metabolic Diseases, The Second Xiangya Hospital of Central South University, Changsha, China.
Division of Endocrinology and Metabolism, Department of Medicine, University of Virginia Health System, Charlottesville, VA, United States.
Front Immunol. 2022 Nov 14;13:968798. doi: 10.3389/fimmu.2022.968798. eCollection 2022.
Fulminant type 1 diabetes may uniquely occur as a fatal adverse event during immune checkpoint inhibitor (ICI) therapy. We investigated the clinical and immunological characteristics of ICI-associated fulminant type 1 diabetes (IFD).
We enrolled 80 patients with IFD (77 cases from the literature), 56 patients with ICI-associated type 1 diabetes (IT1D) (55 cases from the literature), 45 patients with traditional fulminant type 1 diabetes (TFD), and 43 patients with acute-onset type 1 diabetes for comprehensive analysis including islet autoantibodies and subgroup analysis based on ethnic origin.
Patients with IFD accounted for 58.8% (80/136) of patients with ICI-related diabetes. IFD had a more rapid onset than IT1D after ICI therapy (90.5 days 120 days, p <0.05). The onset time and number of infusions after ICI therapy initiation were lower in the antibody-positive IFD group than that in the antibody-negative IFD group (both p <0.001). IFD had a more rapid onset and more serious among Caucasians than that among Asians (p <0.01, p <0.05, respectively), and the prevalence of islet autoantibody positivity in the Caucasian IFD were prominently higher than those in the Asian IFD (p <0.05). Onset age and plasma glucose levels were significantly higher in the IFD group than those in the TFD and acute-onset type 1 diabetes groups. HbA1c levels were slightly higher in patients with IFD than those with TFD.
IFD is relatively common in Caucasian population where TFD is very rare or almost absent. IFD occurrence is significantly related to islet autoantibody status and ethnic origin.
暴发型 1 型糖尿病可能是免疫检查点抑制剂（ICI）治疗中唯一出现的致命不良事件。我们研究了 ICI 相关暴发型 1 型糖尿病（IFD）的临床和免疫学特征。
我们纳入了 80 例 IFD 患者（77 例来自文献）、56 例 ICI 相关 1 型糖尿病（IT1D）患者（55 例来自文献）、45 例传统暴发型 1 型糖尿病（TFD）患者和 43 例急性发作 1 型糖尿病患者进行综合分析，包括胰岛自身抗体和基于种族的亚组分析。
IFD 占 ICI 相关糖尿病患者的 58.8%（80/136）。IFD 在 ICI 治疗后比 IT1D 更快发病（90.5 天 120 天，p <0.05）。在 ICI 治疗开始后，抗体阳性 IFD 组的发病时间和 ICI 输注次数均低于抗体阴性 IFD 组（均 p <0.001）。IFD 在白种人中比在亚洲人中发病更快、更严重（p <0.01，p <0.05），白种人 IFD 中胰岛自身抗体阳性率明显高于亚洲人 IFD（p <0.05）。IFD 组的发病年龄和血浆血糖水平明显高于 TFD 和急性发作 1 型糖尿病组。IFD 组的 HbA1c 水平略高于 TFD 组。
IFD 在白种人中相对常见，而在亚洲人中非常罕见或几乎不存在。IFD 的发生与胰岛自身抗体状态和种族明显相关。
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