Matsuda Takaaki, Osaki Yoshinori, Sekiya Motohiro, Shimano Hitoshi
Department of Endocrinology and Metabolism, University of Tsukuba Hospital, Japan.
Department of Endocrinology and Metabolism, Institute of Medicine, University of Tsukuba, Japan.
J Rural Med. 2025 Apr;20(2):150-155. doi: 10.2185/jrm.2024-030. Epub 2025 Apr 1.
Checkpoint inhibitor-associated autoimmune diabetes mellitus (CIADM), a variant of type 1 diabetes, is a rare immune-related adverse events (irAEs) caused by antibody-based immune checkpoint inhibitors. CIADM typically manifests as fulminant or acute-onset type 1 diabetes in the insulin-depleted state. However, we encountered a patient with slow-onset CIADM who initially presented with hyperglycemia without decreased insulin secretion after treatment with durvalumab (an anti-PD-L1 antibody).
A 60-year-old man diagnosed with small-cell lung cancer on durvalumab combined with dexamethasone treatment experienced an increase in glycated hemoglobin (HbA1c) from 6.4% to 7.8% after three cycles.
Despite preserved endogenous insulin secretion (C-peptide, 2.47 ng/mL with a casual plasma glucose level of 287 mg/dL), basal insulin therapy was initiated considering CIADM. HbA1c levels remained stable (8.5-9.2%) for 3 months but increased to 13.4% at 18 weeks, indicative of CIADM. Declining endogenous insulin secretion resulted in ketosis; however, hyperglycemic crisis was prevented through basal insulin therapy.
We emphasize that CIADM develops gradually and does not always occur in the course of fulminant or acute-onset type 1 diabetes; therefore, early initiation of insulin in the presence of hyperglycemia is crucial to prevent hyperglycemic crises.
检查点抑制剂相关的自身免疫性糖尿病（CIADM）是1型糖尿病的一种变体，是由基于抗体的免疫检查点抑制剂引起的罕见免疫相关不良事件（irAEs）。CIADM通常在胰岛素缺乏状态下表现为暴发性或急性起病的1型糖尿病。然而，我们遇到了一名CIADM起病缓慢的患者，该患者在接受度伐利尤单抗（一种抗PD-L1抗体）治疗后最初表现为高血糖，胰岛素分泌未减少。
一名60岁男性，在接受度伐利尤单抗联合地塞米松治疗时被诊断为小细胞肺癌，三个周期后糖化血红蛋白（HbA1c）从6.4%升至7.8%。
尽管内源性胰岛素分泌保留（C肽，随机血糖水平为287mg/dL时为2.47ng/mL），但考虑到CIADM，仍开始了基础胰岛素治疗。HbA1c水平在3个月内保持稳定（8.5 - 9.2%），但在18周时升至13.4%，提示为CIADM。内源性胰岛素分泌下降导致酮症；然而，通过基础胰岛素治疗预防了高血糖危象。
我们强调，CIADM是逐渐发展的，并不总是在暴发性或急性起病的1型糖尿病过程中发生；因此，在存在高血糖的情况下早期启动胰岛素治疗对于预防高血糖危象至关重要。
