Research Progress on the Mechanisms and Clinical Management of Metabolic Fatty Liver Disease with Diabetes

Abstract

The interaction between metabolic-associated fatty liver disease (MAFLD) and type 2 diabetes mellitus (T2DM) has become a central issue in metabolic syndrome research. The newly proposed definition of MAFLD in 2020 established metabolic dysregulation as the core determinant of its pathogenesis. Globally, approximately 60% of T2DM patients have concurrent MAFLD, and this comorbidity increases the risk of cardiovascular mortality by 2.3-fold. Recent studies have revealed that both conditions share a regulatory mechanism within the “liver-pancreas-gut axis”: hepatic lipotoxicity impairs islet function via exosomal miR-192-5p, while diabetes-related advanced glycation end products (AGEs) activate hepatic stellate cells, accelerating fibrosis. Epigenetic studies have demonstrated that elevated peripheral blood miR-34a levels in MAFLD patients can simultaneously predict both liver fibrosis progression and the onset of diabetic nephropathy, highlighting the bridging role of the microRNA network. In terms of treatment, GLP-1 receptor agonists and SGLT2 inhibitors have shown dual “hepatic-metabolic” benefits. Phase III clinical trials have confirmed that these agents can reduce hepatic fat content by ≥30%. Future research should address the limitations of current biomarkers by leveraging single-cell spatial transcriptomics to dissect hepatic lobular zonation heterogeneity and integrating multi-omics data through artificial intelligence to achieve individualized intervention. This review systematically elucidates the molecular mechanisms underlying the MAFLD-T2DM interaction and explores clinical management strategies, offering novel insights for the comprehensive prevention and treatment of metabolic comorbidities.