随着癌症治疗和支持性护理的进步，出现了越来越多的儿童癌症幸存者，他们承受着与年幼时接受癌症治疗相关的重负。尽管在过去几十年里，儿童癌症幸存者慢性健康问题的发生率总体下降，但某些后遗症，特别是糖尿病（DM）的累积发生率却增加了。这有着重要的意义，因为糖尿病是儿童癌症幸存者中心血管疾病的主要风险因素，同时也是早逝的主要原因之一。癌症幸存者糖尿病的潜在病理生理机制是多因素的。与对照组相比，幸存者发展出糖尿病的年龄较小，这可能反映了这些个体的“加速老化”表型。导致儿童癌症幸存者患糖尿病的治疗相关暴露（如化疗和放射治疗）可能与已知糖尿病风险因素（如年龄、肥胖、种族和民族）更具叠加效应。新兴研究还指出，与老化和癌症治疗相关的糖尿病涉及的细胞过程存在相似之处。尽管如此，个体之间在患糖尿病的风险方面仍有明显的差异，这些差异不能仅通过人口统计和治疗风险因素来解释。最近的研究强调了与一般人群和肿瘤学人群糖尿病风险相关的种系遗传风险因素和表观遗传修饰的作用。本综述总结了我们对儿童癌症幸存者患糖尿病认可的风险因素的当前认知，以帮助制定疾病筛选、预防和治疗的有针对性方法。此外，本文还突出了对个体治疗暴露的相对贡献和独特的作用机制的科学研究差距。2023年版权所有 Bhandari, Armenian, McCormack, Natarajan and Mostoufi-Moab。

With advancements in cancer treatment and supportive care, there is a growing population of childhood cancer survivors who experience a substantial burden of comorbidities related to having received cancer treatment at a young age. Despite an overall reduction in the incidence of most chronic health conditions in childhood cancer survivors over the past several decades, the cumulative incidence of certain late effects, in particular diabetes mellitus (DM), has increased. The implications are significant, because DM is a key risk factor for cardiovascular disease, a leading cause of premature death in childhood cancer survivors. The underlying pathophysiology of DM in cancer survivors is multifactorial. DM develops at younger ages in survivors compared to controls, which may reflect an "accelerated aging" phenotype in these individuals. The treatment-related exposures (i.e., chemotherapy, radiation) that increase risk for DM in childhood cancer survivors may be more than additive with established DM risk factors (e.g., older age, obesity, race, and ethnicity). Emerging research also points to parallels in cellular processes implicated in aging- and cancer treatment-related DM. Still, there remains marked inter-individual variability regarding risk of DM that is not explained by demographic and therapeutic risk factors alone. Recent studies have highlighted the role of germline genetic risk factors and epigenetic modifications that are associated with risk of DM in both the general and oncology populations. This review summarizes our current understanding of recognized risk factors for DM in childhood cancer survivors to help inform targeted approaches for disease screening, prevention, and treatment. Furthermore, it highlights the existing scientific gaps in understanding the relative contributions of individual therapeutic exposures and the mechanisms by which they exert their effects that uniquely predispose this population to DM following cancer treatment.Copyright © 2023 Bhandari, Armenian, McCormack, Natarajan and Mostoufi-Moab.