Association between periodontitis and gestational diabetes mellitus via systemic inflammation: A prospective cohort study

Abstract Background This study aimed to investigate the association between periodontitis severity and the risk of gestational diabetes mellitus (GDM) considering pathways induced by systemic inflammation. Methods Pregnant women with singleton pregnancies aged at least 18 years at 12–20 gestational weeks were enrolled in the study. Logistic and linear regression models were constructed to examine the associations between periodontal status and GDM risk and blood glucose levels. Age‐stratified analyses (≥ 30 vs. < 30 years) were conducted to evaluate potential effect modification. Lastly, mediation analysis was employed to assess the proportion of the association mediated by systemic inflammatory biomarkers. Results Out of 446 participants, the overall incidence of GDM was 26.68%. It increased with the severity of periodontal disease, reaching a 3‐fold higher GDM risk among women with stages II–IV periodontitis compared to healthy controls [17.35% vs. 38.60%; odds ratio (OR) = 3.00, 95% confidence interval (95% CI): 1.38–6.67, p < 0.05]. Stratified analyses showed this association was restricted to women aged ≥ 30 years ( p for interaction < 0.05), with a 4.78‐fold higher GDM risk in women having stages II–IV periodontitis (OR = 4.78, 95% CI: 1.85–13.08; p < 0.05). Even women with stage I periodontitis exhibited a significant association (OR = 2.84, 95% CI: 1.25–6.92, p < 0.05). Mediation analysis revealed that systemic inflammatory markers [white blood cell (WBC), neutrophils, systemic immune inflammation index (SII), aggregate index of systemic inflammation (AISI)] partially mediated the link between stages II–IV periodontitis and GDM, with mediation proportions of 17.85%, 18.61%, 17.32%, and 11.71%, respectively. Conclusion Increasing periodontitis severity was significantly associated with a higher risk of GDM in a dose–response manner in women aged ≥ 30 years, but not in younger women. Besides, systemic inflammation may partially mediate this association, suggesting a biological link between periodontal health and glucose metabolism during pregnancy. Plain Language Summary The relationship between periodontitis severity and gestational diabetes mellitus (GDM) risk has not been systematically characterized, and the biological mechanisms underlying this association are not clear. Our study demonstrated a significant, dose‐dependent association between periodontal disease severity and GDM risk, with a 3‐fold increased likelihood among pregnant women with stages II–IV periodontitis compared to healthy controls. Notably, this association was markedly stronger among women aged ≥ 30 years. Systemic inflammation may partially mediate this association, suggesting a biological link between periodontal health and glucose metabolism during pregnancy.