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纳武单抗剂量递增后发生1型糖尿病:一例报告。

Development of type 1 diabetes mellitus after nivolumab dose escalation: A case report.

作者信息

Mabuchi Sayaka, Adachi Naoko, Nagasawa Atsushi, Nabika Satoshi

机构信息

Department of Human Resources Development for General Practitioner, Shimane Prefectural Central Hospital, Izumo, Japan.

Department of Endocrinology, Shimane Prefectural Central Hospital, Izumo, Japan.

出版信息

Medicine (Baltimore). 2025 Jul 18;104(29):e43356. doi: 10.1097/MD.0000000000043356.

Abstract

RATIONALE

Immune checkpoint inhibitor-induced type 1 diabetes mellitus (ICI-T1DM) is a rare but serious immune-related adverse event associated with programmed cell death-1 inhibitors such as nivolumab. While previous reports have documented its occurrence, the relationship between nivolumab dosing and the onset of ICI-T1DM remains unclear. This study presents a case of ICI-T1DM following a nivolumab dose and includes a literature review.

PATIENT CONCERNS

A man in his 50s (weight: 49.4 kg, body mass index: 17.65 kg/m2) with advanced esophageal cancer had been receiving nivolumab (240 mg every 14 days) for over 2 years without adverse effects. Because of treatment adjustments, the dose was increased to 480 mg and administered every 28 days. Ninety-six days after the dose increase, he developed acute-onset fatigue, anorexia, and thirst.

DIAGNOSES

Laboratory tests confirmed diabetic ketoacidosis with hyperglycemia (582 mg/dL), low C-peptide levels, and negative islet-associated antibodies, leading to the diagnosis of nivolumab-induced fulminant type 1 diabetes mellitus.

INTERVENTIONS

The patient was treated with insulin and discharged after stabilization.

OUTCOMES

This case suggests that higher dose nivolumab may increase the risk of ICI-T1DM, especially in low body-weight individuals.

LESSONS

Given that nivolumab remains effective at lower doses, dose optimization may help mitigate immune-related adverse events while maintaining therapeutic efficacy.

摘要

理论依据

免疫检查点抑制剂诱导的1型糖尿病(ICI-T1DM)是一种罕见但严重的免疫相关不良事件,与纳武利尤单抗等程序性细胞死亡蛋白1抑制剂有关。虽然先前的报告记录了其发生情况,但纳武利尤单抗剂量与ICI-T1DM发病之间的关系仍不清楚。本研究报告了1例纳武利尤单抗给药后发生ICI-T1DM的病例,并进行了文献综述。

患者情况

一名50多岁的男性(体重:49.4千克,体重指数:17.65千克/平方米)患有晚期食管癌,接受纳武利尤单抗(每14天240毫克)治疗超过2年,无不良反应。由于治疗调整,剂量增加至480毫克,每28天给药一次。剂量增加96天后,他出现急性疲劳、厌食和口渴。

诊断

实验室检查证实为糖尿病酮症酸中毒伴高血糖(582毫克/分升)、低C肽水平和胰岛相关抗体阴性,诊断为纳武利尤单抗诱导的暴发性1型糖尿病。

干预措施

患者接受胰岛素治疗,病情稳定后出院。

结果

该病例表明,较高剂量的纳武利尤单抗可能会增加ICI-T1DM的风险,尤其是在低体重个体中。

经验教训

鉴于纳武利尤单抗在较低剂量下仍有效,优化剂量可能有助于减轻免疫相关不良事件,同时保持治疗效果。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5725/12282827/5fb48148db5d/medi-104-e43356-g001.jpg

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