Department of Pharmacology-Clinical Pharmacology Unit, Faculty of Medicine, National and Kapodistrian University of Athens, 11527 Athens, Greece.
Int J Mol Sci. 2023 Apr 21;24(8):7630. doi: 10.3390/ijms24087630.
The rubric of immune-related (ir) diabetes mellitus (DM) (irDM) encompasses various hyperglycemic disorders related to immune checkpoint inhibitors (ICPis). Beyond sharing similarities with conventional DM, irDM is a distinct, yet important, entity. The present narrative review provides a comprehensive overview of the literature regarding irDM published in major databases from January 2018 until January 2023. Initially considered rare, irDM is increasingly being reported. To advance the knowledge of irDM, the present review suggests a concerted vision comprising two intertwined aspects: a scientific-centered and a patient-centered view. The scientific-centered aspect addresses the pathophysiology of irDM, integrating: (i) ICPi-induced pancreatic islet autoimmunity in genetically predisposed patients; (ii) altered gut microbiome; (iii) involvement of exocrine pancreas; (iv) immune-related acquired generalized lipodystrophy. The patient-centered aspect is both nurtured by and nurturing the four pillars of the scientific-centered aspect: awareness, diagnosis, treatment, and monitoring of irDM. The path forward is a multidisciplinary initiative towards: (i) improved characterization of the epidemiological, clinical, and immunological profile of irDM; (ii) standardization of reporting, management, and surveillance protocols for irDM leveraging global registries; (iii) patient stratification according to personalized risk for irDM; (iv) new treatments for irDM; and (v) uncoupling ICPi efficacy from immunotoxicity.
免疫相关(ir)糖尿病(DM)(irDM)的范畴包括了各种与免疫检查点抑制剂(ICPis)相关的高血糖疾病。除了与传统 DM 具有相似之处外,irDM 还是一种独特且重要的实体疾病。本综述性文章全面概述了 2018 年 1 月至 2023 年 1 月期间在主要数据库中发表的有关 irDM 的文献。尽管最初认为 irDM 较为罕见,但目前报道的病例却越来越多。为了深入了解 irDM,本综述提出了一个由两个相互交织的方面组成的协同愿景:以科学为中心和以患者为中心的观点。以科学为中心的方面涉及 irDM 的病理生理学,整合了:(i)ICPi 诱导的遗传易感患者胰岛自身免疫;(ii)肠道微生物组的改变;(iii)外分泌胰腺的参与;(iv)免疫相关获得性全身性脂肪营养不良。以患者为中心的方面既是科学为中心方面的四个支柱(即 irDM 的意识、诊断、治疗和监测)的培育者,也是受益者。未来的发展方向是一个多学科的倡议,旨在:(i)改善 irDM 的流行病学、临床和免疫学特征的描述;(ii)利用全球登记处标准化 irDM 的报告、管理和监测方案;(iii)根据 irDM 的个体化风险对患者进行分层;(iv)为 irDM 开发新的治疗方法;以及(v)将 ICPi 的疗效与免疫毒性脱钩。