Abstract
Background: The global prevalence of type 2 diabetes mellitus (T2DM) with liver fibrosis is rising, with T2DM identified as an independent risk factor and key prognostic factor for liver fibrosis. However, the underlying mechanisms remain unclear. Methods: To explore the shared pathogenesis of liver fibrosis and T2DM, we analyzed gene expression profiles from the GEO database. The co-differentially expressed genes (co-DEGs) were identified and subsequently analyzed through functional enrichment, protein-protein interaction (PPI) network construction, transcription factor prediction, and drug prediction. Machine learning algorithms were then applied to identify key genes. Results: A total of 175 co-DEGs were identified. Functional enrichment analysis indicated their involvement in extracellular matrix (ECM) remodeling, inflammation, and the PI3K/Akt signaling pathway. Through PPI network analysis and four algorithms, eight hub genes were identified, including SPARC, COL4A2, THBS1, LUM, TIMP3, COL3A1, IGFBP7, and FSTL1, with THBS1 being recognized as a key gene by machine learning. The upregulation of THBS1 was observed in both diseases, and it is closely related to the progression of liver fibrosis and T2DM. Transcription factor analysis detected 29 regulators of these hub genes. Drug prediction analysis suggested that retinoic acid may serve as a potential therapeutic agent. Conclusions: This study provides novel insights into the shared pathogenesis of liver fibrosis and T2DM and offer potential targets for clinical intervention.