Monocyte CCL2 signaling possibly contributes to increased asthma susceptibility in type 2 diabetes.

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.