Maternal Serum Netrin-1 Levels in Pregnancies Complicated by Gestational Diabetes Mellitus
Objective: Gestational diabetes mellitus (GDM) is associated with metabolic and vascular disturbances, yet its underlying biological mechanisms remain incompletely understood. Netrin-1, a multifunctional protein involved in angiogenesis, inflammation, and endothelial homeostasis, has been implicated in metabolic disorders; however, clinical data in GDM are limited. This study aimed to evaluate maternal netrin-1 levels in pregnancies complicated by GDM and to assess their associations with clinical parameters.
Methods: This prospective case–control study included 45 pregnant women with GDM and 80 healthy pregnant controls between 24 and 28 weeks of gestation. Serum netrin-1 concentrations were measured using enzyme-linked immunosorbent assay. Clinical characteristics, glycemic parameters, and pregnancy outcomes were recorded. Receiver operating characteristic (ROC) analysis assessed the discriminatory performance of netrin-1 for GDM, and correlation and multivariable regression analyses identified associations after adjustment for selected covariates.
Results: Serum netrin-1 levels were significantly lower in GDM group compared with controls (P<0.001). Netrin-1 concentrations showed significant inverse correlations with fasting plasma glucose (r=−0.446, P=0.002) and HbA1c (r=−0.623, P<0.001). ROC analysis identified an optimal cut-off value of 0.09 ng/mL for discriminating GDM, yielding a sensitivity of 68.9% and a high specificity of 98.8% (AUC=0.861), indicating good discriminative performance. In multivariable analysis adjusted for age, body mass index, and parity, log-transformed netrin-1 levels were associated with GDM (P<0.001).
Conclusion: Maternal netrin-1 levels are significantly reduced in pregnancies complicated by GDM and are closely associated with glycemic dysregulation. Netrin-1 may reflect underlying metabolic and vascular alterations and could be considered as a complementary biomarker rather than a standalone diagnostic tool in GDM.
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Article Information
- Article Type Research Article
- Submitted April 9, 2026
- Accepted May 9, 2026
- Published May 22, 2026
- Issue 2026: Online First
- Section Research Article
- Categories
