Diagnostic and Predictive Value of Serum Sestrin-2 and Hypoxia-Inducible Factor-1alpha in Gestational Diabetes Mellitus: A Case–Control Study

Background: Gestational diabetes mellitus (GDM) is a common metabolic disorder characterized by glucose intolerance and associated with adverse maternal and fetal outcomes. Emerging evidence suggests that oxidative stress and hypoxia-related pathways may contribute to its pathophysiology. This study aimed to evaluate the diagnostic performance of serum sestrin-2 (SESN-2) and hypoxia-inducible factor-1alpha (HIF-1α) as potential biomarkers in GDM. Methods: In this case–control study, 100 pregnant women (50 with GDM and 50 controls) were enrolled. Serum SESN-2 and HIF-1α levels were measured using enzyme-linked immunosorbent assay (ELISA). Results: Patients with GDM showed significantly higher body mass index, glucose levels, glycated hemoglobin (HbA1c), insulin, and C-reactive protein (CRP) (all p < 0.05). SESN-2 and HIF-1α levels were significantly elevated (both p < 0.0001). Receiver operating characteristic (ROC) analysis showed area-under-the-curve (AUC) values of 0.799 for SESN-2 and 0.769 for HIF-1α, which increased to 0.909 when combined. Both biomarkers were independently associated with GDM in multivariable analysis. Conclusions: SESN-2 and HIF-1α levels are elevated in GDM and are associated with its presence. These biomarkers demonstrated moderate diagnostic performance, and their combined use improved discrimination; however, they should be considered complementary rather than standalone diagnostic tools. Given the cross-sectional design, the findings reflect associations rather than predictive relationships, and further prospective studies are required to clarify their clinical utility.