1型糖尿病（T1DM）是免疫检查点抑制剂（ICIs）引起的罕见但严重的免疫相关不良事件（irAE）。我们的目标是通过临床、免疫学和蛋白质组学数据的分析，表征与ICI引起的T1DM相关的治疗结果。本研究是对于实体肿瘤患者的单中心病例系列，这些患者接受了ICIs治疗，并随后被新诊断为T1DM。我们使用ICD代码和C肽水平来识别需要进行病历审查以确认ICI引起的T1DM的患者。基线血标本用于研究蛋白质组学和免疫表型的变化。在2011年至2023年期间，在Huntsman癌症研究所接受ICIs治疗的3744名患者中，有18名被确认为ICI引起的T1DM（占比0.48%）。其中，11名患者接受了抗PD1单药治疗，4名患者接受了抗PD1联合化疗或靶向治疗，而3名患者接受了伊比利莫和尼伐莫的联合治疗。发病时间的平均为218天（范围为22-418天）。患者在诊断前的2-3周内出现了突然升高的血清葡萄糖。其中16人（占89%）出现了糖尿病酮症酸中毒。其中12名患者中有3名出现了T1DM相关的自身抗体。所有T1DM患者在随访期间均需要胰岛素来维持。在中位随访时间为21.9个月（范围为8.4-82.4个月），黑色素瘤组中没有患者因疾病恶化或死亡。在黑色素瘤组中，最佳疗效为2个完全缓解和2个部分缓解的病例；而在辅助组中，没有疾病复发的情况。基线血液的蛋白质组学分析表明，ICI引起的T1DM队列中具有低炎症指标（IL-6、OSMR）和高代谢指标（GLO1、DXCR）。我们的病例系列研究展示了ICI引起的T1DM的快速发病和不可逆性。ICI引起的T1DM的黑色素瘤患者表现出良好的临床反应和生存。有限的蛋白质组学数据还显示出独特的蛋白质组学特征。我们的研究有助于临床医生了解这种罕见irAE的独特临床表现和长期预后，以制定最佳的临床管理策略。

Type 1 diabetes mellitus (T1DM) is a rare, but serious immune-related adverse event (irAE) of immune checkpoint inhibitors (ICIs). Our goal was to characterize treatment outcomes associated with ICI-induced T1DM through analysis of clinical, immunological and proteomic data.This was a single-center case series of patients with solid tumors who received ICIs and subsequently had a new diagnosis of T1DM. ICD codes and C-peptide levels were used to identify patients for chart review to confirm ICI-induced T1DM. Baseline blood specimens were studied for proteomic and immunophenotypic changes.Between 2011 and 2023, 18 of 3744 patients treated at Huntsman Cancer Institute with ICIs were confirmed to have ICI-induced T1DM (0.48%). Eleven of the 18 patients received anti-PD1 monotherapy, 4 received anti-PD1 plus chemotherapy or targeted therapy, and 3 received ipilimumab plus nivolumab. The mean time to onset was 218 days (range 22-418 days). Patients had sudden elevated serum glucose within 2-3 weeks prior to diagnosis. Sixteen (89%) presented with diabetic ketoacidosis. Three of 12 patients had positive T1DM-associated autoantibodies. All patients with T1DM became insulin-dependent through follow-up. At median follow-up of 21.9 months (range 8.4-82.4), no patients in the melanoma group had progressed or died from disease. In the melanoma group, best responses were 2 complete response and 2 partial response while on active treatment; none in the adjuvant group had disease recurrence. Proteomic analysis of baseline blood suggested low inflammatory (IL-6, OSMR) markers and high metabolic (GLO1, DXCR) markers in ICI-induced T1DM cohort.Our case series demonstrates rapid onset and irreversibility of ICI-induced T1DM. Melanoma patients with ICI-induced T1DM display excellent clinical response and survival. Limited proteomic data also suggested a unique proteomic profile. Our study helps clinicians to understand the unique clinical presentation and long-term outcomes of this rare irAE for best clinical management.Copyright © 2023 Marsiglio, McPherson, Kovacsovics-Bankowski, Jeter, Vaklavas, Swami, Grossmann, Erickson-Wayman, Soares, Kerrigan, Gibson, Doherty, Hyngstrom, Hardikar and Hu-Lieskovan.