OBJECTIVE To conduct a multi-centre case series characterising the clinical characteristics at presentation and pancreatic volume changes of patients with checkpoint inhibitor associated autoimmune diabetes (CIADM). RESEARCH DESIGN AND METHODS Electronic medical records were reviewed with 36 consecutive patients identified with CIADM, as defined by: i) previous immune checkpoint inhibitor (ICI) therapy; ii) new onset hyperglycaemia (BGL>=11.1mmol/L and/or HbA1c >= 6.5%); and iii) insulin deficiency (C-peptide <0.4nmol/L or diabetic ketoacidosis (DKA)) within 1 month of presentation. Pancreatic volume was available and measured using CT volumetry for 17 patients with CIADM, and 3 sets of control patients: 7 with ICI-related pancreatitis; 13 with asymptomatic ICI -related lipase elevation; and 11 ICI treated controls for comparison. RESULTS All patients had either anti-PD1 or anti-PD-L1 therapy. Median time from ICI commencement to CIADM diagnosis was 15 weeks. At presentation, 25 (69%) had DKA, 27 (84%) had low C-peptide and by 1 month, 100% had low C-peptide. Traditional type 1 diabetes (T1D) autoantibodies were positive in 15/35 (43%). Lipase was elevated in 13/27 (48%) at presentation. In 4 patients with longitudinal lipase testing, elevated levels peaked 1 month prior to CIADM diagnosis. Pancreatic volume was lower pre-ICI in CIADM patients compared to controls, and demonstrated a mean decline of 41% from pre-treatment to 6 months post CIADM diagnosis. CONCLUSIONS Pronounced biochemical and radiologic changes occur during CIADM pathogenesis. Rapid loss of C-peptide is a distinct characteristic that can be used to aid diagnosis as autoantibodies are often negative.

中文翻译：

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检查点抑制剂相关的自身免疫性糖尿病的特征是C肽丢失和胰腺萎缩。

目的 开展多中心病例系列研究，描述检查点抑制剂相关自身免疫性糖尿病 (CIADM) 患者的临床特征和胰腺体积变化。研究设计和方法 对 36 名被确定患有 CIADM 的连续患者的电子病历进行了审查，其定义如下： i) 既往免疫检查点抑制剂 (ICI) 治疗；ii) 新发高血糖（BGL>=11.1mmol/L 和/或 HbA1c>=6.5%）；iii) 就诊 1 个月内出现胰岛素缺乏（C 肽 <0.4nmol/L 或糖尿病酮症酸中毒 (DKA)）。17 名 CIADM 患者和 3 组对照患者的胰腺体积可用并使用 CT 容量法进行测量：7 名患有 ICI 相关胰腺炎；13 例无症状 ICI 相关脂肪酶升高；和 11 个 ICI 处理对照进行比较。结果 所有患者均接受了抗 PD1 或抗 PD-L1 治疗。从 ICI 开始到 CIADM 诊断的中位时间为 15 周。目前，25 名 (69%) 患者患有 DKA，27 名 (84%) 患者 C 肽水平较低，到 1 个月后，100% 的患者 C 肽水平较低。传统 1 型糖尿病 (T1D) 自身抗体在 15/35 (43%) 中呈阳性。13/27 (48%) 就诊时脂肪酶升高。在 4 名接受纵向脂肪酶检测的患者中，其水平在 CIADM 诊断前 1 个月达到峰值。与对照组相比，CIADM 患者在 ICI 前的胰腺体积较低，并且从治疗前到 CIADM 诊断后 6 个月平均下降了 41%。结论 CIADM 发病过程中会发生明显的生化和放射学变化。C 肽快速丢失是一个独特的特征，可用于帮助诊断，因为自身抗体通常呈阴性。