Non-linear relationship between the high-density lipoprotein cholesterol and Gestational Diabetes risk: An Analysis Based on Data from a Prospective Study

Objective: While pregnancy-associated metabolic adaptations are increasingly understood, the relationship between high-density lipoprotein cholesterol (HDL-C) and gestational diabetes mellitus (GDM) remains poorly characterized. This investigation explored potential nonlinear associations between maternal HDL-C concentrations and subsequent GDM development in Korean women. Methods: The study followed 590 pregnant women carrying single fetuses who underwent health screenings between 10 and 14 weeks of gestation from November 2014 through July 2016.Employing binary and two-piecewise logistic regression analyses, we comprehensively dissected the associations between HDL-C and GDM risk. Results: Within our cohort, GDM manifested in 6.27% (95% CI: 4.3%1-8.23%) of participants. Initial logistic regression demonstrated an inverse relationship between HDL-C concentrations and GDM probability (unadjusted model: OR=0.97, 95% CI: 0.94-0.99, P=0.0094; partially adjusted model: OR=0.96, 95% CI: 0.94-0.99, P=0.0120). However, comprehensive confounder adjustment revealed no significant linear association (OR=0.98, 95% CI: 0.95-1.01, P=0.1409). Importantly, segmented regression identified a critical HDL-C threshold at 49.8 mg/dL. For concentrations below this value, HDL-C exhibited strong protective associations (OR=0.82, 95% CI: 0.70-0.95, P=0.0105), while no significant relationship existed above this threshold (OR=1.01, 95% CI: 0.98-1.05, P=0.4494). Below this inflection point, HDL-C levels showed a significant correlation with a lower risk of GDM (OR=0.82, 95% CI: 0.70-0.95, P=0.0105), while no significant correlation was observed above the inflection point (OR=1.01, 95% CI: 0.98-1.05, P=0.4494). Conclusion: This investigation challenges conventional metabolic paradigms by demonstrating threshold-dependent associations between HDL-C and GDM risk. Protective effects appear concentrated exclusively below a specific inflection point, suggesting targeted lipid optimization strategies may benefit maternal glycemic health during pregnancy.