Effects of metformin on serum miRNA expression and target gene regulation in prediabetic patients

Prediabetes, also known as impaired glucose tolerance (IGT), is a common metabolic disorder and is often considered a risk factor for the development of diabetes. Metformin (MET) is a widely used medication for the treatment of diabetes and has the potential to improve insulin sensitivity and blood sugar control. This work aimed to investigate the impact of MET treatment on serum miRNA expression in IGT patients and explore the quantitative changes in miRNA after MET treatment.

Peripheral blood samples were collected from 6 prediabetic patients, and serum miRNA expression was analyzed before and after MET treatment. Differentially expressed miRNAs were identified, and gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and protein-protein interaction (PPI) network analyses were performed to explore the biological processes and pathways involved.

Fourteen miRNAs (8 upregulated and 6 downregulated) were identified in IGT patients. The top 5 miRNAs based on differential fold change (FC) were identified. Following MET treatment, hsa-miR-455-5p, hsa-miR-505-3p, hsa-miR-21-5p, and hsa-miR-33a-5p were downshifted, while hsa-miR-96-5p was increased in patients (P < 0.05). The differentially expressed miRNAs were linked with collagen catabolic process (CCP), postsynaptic density (PD), and extracellular matrix structural constituent (EMSC). Enrichment analysis (EA) revealed involvement in signaling pathways like advanced glycation end products (AGEs) and their receptor (RAGE) signaling pathway in diabetic complications, signaling pathways regulating pluripotency of stem cells, and TNF signaling pathway.

MET modulates miRNA expression in prediabetic patients, potentially influencing pathways related to insulin sensitivity and metabolic regulation. These findings may guide future therapeutic strategies for early diabetes intervention.