Luo Tian, Guo Weihong, Ji Wentao, Du WeiWei, Lv Yanhua, Feng Zhijun
Department of Respiratory and Critical Care Medicine, The People's Hospital of Sishui, Jining, 273200, Shandong, China.
Zhongshan City People's Hospital, Xinxiang Medical University, Xinxiang, 453003, Henan, China.
Sci Rep. 2025 Mar 28;15(1):10768. doi: 10.1038/s41598-025-95039-1.
In recent years, the respiratory system has been increasingly recognized as a key target organ in diabetes. Although observational studies have established significant clinical associations between type 2 diabetes (T2D), antidiabetic medication use, and asthma, the causal relationships and underlying molecular mechanisms remain unclear. This study employed a bidirectional two-sample Mendelian randomization (MR) approach combined with bioinformatics analysis to explore the causal relationships between T2D and asthma subtypes and complications, with a focus on immune-regulatory mechanisms. The MR analysis utilized inverse-variance weighted (IVW) and meta-analysis methods to evaluate overall effects, with sensitivity analyses confirming the robustness of the findings. Bioinformatics analysis focused on differential gene expression and pathway enrichment to identify potential molecular networks. The MR analysis showed that T2D has a significant positive causal effect on asthma (P < 0.05), with severe autoimmune T2D showing strong associations with specific asthma subtypes (eosinophilic and mixed asthma) and complications (e.g., acute respiratory infections and pneumonia) (P < 0.05). Bioinformatics analysis identified the monocyte-CCL2 signaling axis as a key mechanism linking T2D and asthma, where hyperglycemia-induced monocyte activation may promote asthma development. These findings reveal shared inflammatory pathways and deepen our understanding of the molecular mechanisms linking these two chronic diseases.
近年来，呼吸系统日益被视为糖尿病的关键靶器官。尽管观察性研究已证实2型糖尿病（T2D）、抗糖尿病药物使用与哮喘之间存在显著的临床关联，但其因果关系和潜在分子机制仍不清楚。本研究采用双向双样本孟德尔随机化（MR）方法并结合生物信息学分析，以探讨T2D与哮喘亚型及并发症之间的因果关系，重点关注免疫调节机制。MR分析采用逆方差加权（IVW）和荟萃分析方法评估总体效应，敏感性分析证实了研究结果的稳健性。生物信息学分析聚焦于差异基因表达和通路富集，以识别潜在的分子网络。MR分析表明，T2D对哮喘有显著的正向因果效应（P < 0.05），严重自身免疫性T2D与特定哮喘亚型（嗜酸性粒细胞性和混合性哮喘）及并发症（如急性呼吸道感染和肺炎）有强关联（P < 0.05）。生物信息学分析确定单核细胞-CCL2信号轴是连接T2D和哮喘的关键机制，高血糖诱导的单核细胞激活可能促进哮喘发展。这些发现揭示了共同的炎症通路，加深了我们对连接这两种慢性疾病的分子机制的理解。
