Data Sheet 1_Association between gestational diabetes mellitus and risk of breast cancer: a systematic review and meta-analysis.docx

BackgroundGestational diabetes mellitus (GDM), a prevalent metabolic complication during pregnancy, has a global prevalence of approximately 14%. Its onset is closely associated with insulin resistance, insufficient compensatory function of β - cells, and abnormal placental function. Epidemiological studies have indicated that type 2 diabetes is an independent risk factor for breast cancer. However, the association between GDM and the risk of breast cancer remains controversial.
ObjectiveThis systematic review and meta-analysis aim to comprehensively evaluate the association between GDM and the risk of breast cancer and explore its underlying mechanisms.
MethodsThis study systematically searched PubMed, Web of Science, Scopus, EMBASE, and the Cochrane Library databases, covering the period from establishing each database until April 14, 2025. Two researchers extracted relevant data and assessed the quality of included studies using the Newcastle-Ottawa Scale. The study evaluated inter-study heterogeneity using the I² statistic. Based on the magnitude of heterogeneity, fixed-effect or random-effect models were employed to calculate the pooled hazard ratio (HR) and its corresponding 95% confidence interval (CI). Additionally, subgroup analyses, sensitivity analyses, funnel plot analyses, and publication bias assessments were performed. All data analyses were conducted using STATA 17 software.
ResultsThe overall analysis revealed no significant association between GDM and breast cancer risk (HR=1.03, 95%CI: 0.92-1.15). However, subgroup analysis revealed significant regional heterogeneity: within the regional subgroups, North American results showed an association between GDM and a reduced breast cancer risk (HR=0.89, 95%CI: 0.84-0.95), whereas Asian findings suggested an association with an increased risk (HR=1.23, 95%CI: 1.15-1.31). No significant associations were observed in subgroups based on study design (cohort/case-control) or follow-up duration (short-term/long-term). Sensitivity analysis demonstrated robust results, and there was no publication bias in this study.
ConclusionIn summary, there is no significant association between GDM and breast cancer risk overall. However, notable regional heterogeneity exists: in the North American subgroup, GDM is associated with a reduced risk of breast cancer, while in the Asian subgroup, GDM is significantly associated with an increased risk of breast cancer.
Systematic Review Registrationhttps://www.crd.york.ac.uk/PROSPERO/, identifier CRD420251032589.

背景
妊娠期糖尿病（Gestational diabetes mellitus, GDM）是一种妊娠期常见的代谢并发症，全球患病率约为14%。其发病与胰岛素抵抗、β细胞代偿功能不足以及胎盘功能异常密切相关。流行病学研究表明，2型糖尿病是乳腺癌的独立危险因素。然而，妊娠期糖尿病与乳腺癌发病风险之间的关联仍存在争议。
目的
本项系统评价与Meta分析旨在全面评估妊娠期糖尿病与乳腺癌发病风险之间的关联，并探讨其潜在机制。
方法
本研究系统检索了PubMed、Web of Science、Scopus、EMBASE及Cochrane Library数据库，检索时限为各数据库建库起至2025年4月14日。由两名研究者独立提取相关数据，并采用纽卡斯尔-渥太华量表（Newcastle-Ottawa Scale）对纳入研究的质量进行评价。本研究使用I²统计量评估研究间异质性，根据异质性大小选用固定效应模型或随机效应模型计算合并风险比（hazard ratio, HR）及其对应的95%置信区间（confidence interval, CI）。此外，本研究还开展了亚组分析、敏感性分析、漏斗图分析及发表偏倚评估。所有数据分析均采用STATA 17软件完成。
结果
总体分析显示，妊娠期糖尿病与乳腺癌发病风险无显著关联（HR=1.03，95%CI：0.92~1.15）。但亚组分析显示存在显著区域异质性：在区域亚组中，北美亚组结果提示妊娠期糖尿病与乳腺癌发病风险降低相关（HR=0.89，95%CI：0.84~0.95），而亚洲亚组结果则显示其与发病风险升高相关（HR=1.23，95%CI：1.15~1.31）。在基于研究设计（队列研究/病例对照研究）或随访时长（短期/长期）的亚组中，未观察到显著关联。敏感性分析证实结果稳健，本研究未存在发表偏倚。
结论
综上，妊娠期糖尿病与乳腺癌发病风险总体上无显著关联，但存在显著的区域异质性：北美亚组中，妊娠期糖尿病与乳腺癌发病风险降低相关；而亚洲亚组中，妊娠期糖尿病与乳腺癌发病风险升高存在显著关联。
系统评价注册信息
https://www.crd.york.ac.uk/PROSPERO/，注册号为CRD420251032589。