Watanabe Mayu, Eguchi Jun, Takamoto Atsushi, Kanzaki Hiromitsu, Noda Yohei, Kagawa Syunsuke, Wada Jun
Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.
Department of Diabetology and Metabolism, NHO Okayama Medical Center, Okayama, Japan.
Front Endocrinol (Lausanne). 2024 Dec 11;15:1439705. doi: 10.3389/fendo.2024.1439705. eCollection 2024.
Although immune checkpoint inhibitors (ICIs) are effective cancer drugs, ICI-induced diabetes is a rare but a life-threatening adverse event for patients. The deleterious action of ICI on pancreatic beta-cell function is a concern. However, the influence of ICI on insulin synthesis and secretion in patients with cancer without diabetes remains unknown.
This study included 87 patients diagnosed with advanced cancer. Glucose metabolism markers (HbA1c, HOMA-IR) and indicators of insulin secretory capacity (HOMA-beta, C-peptide) were prospectively evaluated in patients with ICI-treated cancers to determine their association with cancer prognosis.
Patients with overall survival (OS) ≥ 7 months had substantially higher HOMA-beta levels at baseline (p=0.008) and 1 month after ICI administration (p=0.006) compared to those with OS <7 months. The median OS was significantly longer in patients with HOMA-beta ≥ 64.24 (13 months, 95%CI: 5.849-20.151, 37 events) than in those with HOMA-beta < 64.24 (5 months, 95%CI: 3.280-6.720, 50 events) (p=0.013). Further, the median progression-free survival (PFS) was significantly longer in patients with HOMA-beta ≥ 66.43 (4 months, 95%CI: 3.073-4.927, 33 events) than in those with HOMA-beta < 66.43 (2 months, 95%CI: 1.410-2.590, 54 events) (p=0.025). Additionally, multivariable logistic regression analysis revealed that a HOMA-beta value ≥ 64.24 independently predicted longer OS in ICI-treated patients.
Pre-ICI HOMA-beta level is linked to longer OS in ICI-treated patients. This connection is significant and shows that insulin secretory capacity may predict ICI efficacy.
尽管免疫检查点抑制剂（ICIs）是有效的抗癌药物，但ICI诱发的糖尿病对患者来说是一种罕见但危及生命的不良事件。ICI对胰腺β细胞功能的有害作用令人担忧。然而，ICI对无糖尿病癌症患者胰岛素合成和分泌的影响尚不清楚。
本研究纳入了87例诊断为晚期癌症的患者。对接受ICI治疗的癌症患者前瞻性评估葡萄糖代谢标志物（糖化血红蛋白、胰岛素抵抗指数）和胰岛素分泌能力指标（胰岛β细胞功能指数、C肽），以确定它们与癌症预后的关联。
总生存期（OS）≥7个月的患者在基线时（p=0.008）和ICI给药后1个月（p=0.006）的胰岛β细胞功能指数水平显著高于OS<7个月的患者。胰岛β细胞功能指数≥64.24的患者中位OS（13个月，95%CI：5.849-20.151，37例事件）显著长于胰岛β细胞功能指数<64.24的患者（5个月，95%CI：3.280-6.720，50例事件）（p=0.013）。此外，无进展生存期（PFS）中位数在胰岛β细胞功能指数≥66.43的患者中（4个月，95%CI：3.073-4.927，33例事件）显著长于胰岛β细胞功能指数<66.43的患者（2个月，95%CI：1.410-2.590，54例事件）（p=0.025）。此外，多变量逻辑回归分析显示，胰岛β细胞功能指数≥64.24独立预测接受ICI治疗患者的OS更长。
ICI治疗前的胰岛β细胞功能指数水平与接受ICI治疗患者的更长OS相关。这种关联很显著，表明胰岛素分泌能力可能预测ICI疗效。
