Periodontitis and Gestational Diabetes Mellitus: Evidence for a Potential Biological Link.

PURPOSE: This study aimed to investigate the potential association between gestational diabetes mellitus (GDM) and periodontitis (PD) and to explore possible biological mechanisms underlying this link. MATERIALS AND METHODS: In the first part of this study, a two-sample Mendelian randomisation (MR) analysis was conducted to evaluate the potential effect of PD on the risk of GDM, and vice versa. In the second part, transcriptomic data and network-based bioinformatics analyses were integrated, including differential expression analysis and protein-protein interaction (PPI) network construction, to screen for common differentially expressed genes and significantly enriched biological pathways. In the third part, a simplified in vitro β-cell challenge system was established using the human pancreatic β-cell line EndoC-βH1. Cells were exposed to high-glucose and progesterone conditions with or without Porphyromonas gingivalis to examine inflammatory and oxidative stress responses. Differences in the expression of MR-genes, inflammatory cytokines, and reactive oxidative species were evaluated. All analyses were performed using R version 4.2.2 (R CoreTeam, Vienna, Austria). RESULTS: The forward MR analysis showed evidence consistent with a modest positive association of genetically predicted PD with GDM risk (OR = 1.14, P = 0.006), whereas the reverse analysis did not provide evidence for an association of genetically predicted GDM with PD risk (OR = 1.08, P = 0.222). Sensitivity analyses supported the robustness of the MR results. Transcriptomic bioinformatic analyses identified multiple key genes that were dysregulated in both PD and GDM, including inflammatory mediators (IL1RN and TGFB1) and metabolic regulators (AKT1, NOS3, and TCF7L2). Functional enrichment revealed that the overlapping genes were mainly involved in critical biological processes like apoptotic signalling, cell adhesion, and inflammatory responses. The PPI network suggested a synergistic role of PD and GDM in inflammation and metabolic regulation. Compared with the GDM model, β-cells in the GDM+PD model exhibited significantly enhanced inflammatory responses and oxidative stress. Additionally, the MR-genes showed significant expression changes in the GDM+PD model: HSPBAP1, APBA1, and SHC4 were upregulated, whereas CDH1, NDUFAF6, and DGKB were downregulated. CONCLUSION: These findings provide evidence consistent with a potential biological link between PD and GDM, in which periodontal infection-related inflammatory responses and oxidative stress may aggravate β-cell stress under GDM-like conditions.