PDF(Pubmed)
Abstract：
Immune checkpoint inhibitors (ICIs) are widely used in cancer treatment; however, they can lead to immune-related adverse events, including immune checkpoint inhibitor-induced type 1 diabetes mellitus (ICI-T1DM). While fulminant T1DM is common in East Asia, ICI-T1DM has predominantly been reported in Western countries. In this report, we present the case of a 66-year-old Japanese man with type 2 diabetes mellitus undergoing dialysis for diabetic nephropathy. The patient was diagnosed with left upper lobe lung cancer, and treatment with nivolumab and ipilimumab was initiated. After 48 days, the patient experienced impaired consciousness and difficulty moving. His blood glucose levels were 815 mg/dL, and metabolic acidosis was detected, leading to a diagnosis of diabetic ketoacidosis. The patient was subsequently treated with continuous intravenous insulin. However, his C-peptide levels rapidly depleted, and new-onset ICI-T1DM was diagnosed. Although most Japanese patients with ICI-T1DM test negative for glutamic acid decarboxylase (GAD) antibodies, this case exhibited a strong positivity. Thus, we reviewed the literature on 15 similar Japanese cases, revealing a mean HbA1c level at onset of 8.7% and a mean time from ICI administration to onset of 9.7 weeks, which was shorter than that in GAD-negative cases. Moreover, human leukocyte antigen typing revealed five cases of DRB1*04:05-DQB1*04:01, including the present case, and one case of DRB1*09:01-DQB1*03:03, both of which were susceptible to T1DM haplotypes. These findings suggest that GAD antibody positivity may be associated with acute onset and disease progression in some cases of Japanese patients with ICI-T1DM. Given that the prediction of new-onset ICI-T1DM is challenging, monitoring GAD antibody levels might be useful. However, further studies with large sample sizes and validation across different racial and ethnic populations are warranted.
摘要：
免疫检查点抑制剂(ICIs)广泛用于癌症治疗;然而,它们会导致免疫相关的不良事件，包括免疫检查点抑制剂诱导的1型糖尿病（ICI-T1DM）。暴发性T1DM在东亚很常见，ICI-T1DM主要在西方国家报道。在这份报告中,我们介绍一例66岁的日本2型糖尿病患者,因糖尿病肾病接受透析治疗.病人被诊断为左上叶肺癌,开始接受纳武单抗和伊匹单抗治疗.48天后,患者出现意识受损和移动困难。他的血糖水平为815毫克/分升，并检测到代谢性酸中毒，导致糖尿病酮症酸中毒的诊断。患者随后接受连续静脉内胰岛素治疗。然而,他的C肽水平迅速耗尽，诊断为新发ICI-T1DM。尽管大多数日本ICI-T1DM患者的谷氨酸脱羧酶（GAD）抗体检测呈阴性，这个案例表现出强烈的积极性。因此，我们回顾了15个类似的日本案例的文献，显示发病时的平均HbA1c水平为8.7％，从ICI给药到发病的平均时间为9.7周，短于GAD阴性病例。此外，人类白细胞抗原分型显示5例DRB1*04:05-DQB1*04:01，包括本案，1例DRB1*09:01-DQB1*03:03，均易感T1DM单倍型。这些发现表明，在某些日本ICI-T1DM患者中，GAD抗体阳性可能与急性发作和疾病进展有关。鉴于新发ICI-T1DM的预测具有挑战性，监测GAD抗体水平可能是有用的。然而,有必要在不同种族和民族人群中进行大样本量和验证的进一步研究.
