Diagnostic Significance of Serum CTRP9 Levels in Gestational Diabetes Mellitus: A Case-Control Study

Abstract

Background: C1q/tumor necrosis factor-related protein 9 (CTRP9) is an adiponectin paralog that modulates glucose and lipid metabolism through AMP-activated protein kinase (AMPK) signaling. Its diagnostic relevance in gestational diabetes mellitus (GDM) remains incompletely defined and is reported inconsistently across studies.

Objectives: To evaluate serum CTRP9 concentrations in women with GDM compared with normoglycemic pregnant controls, and to determine its diagnostic performance, independent predictive value, and relationship with maternal and neonatal outcomes.

Materials and Methods: A prospective case-control study was conducted on 120 pregnant women (60 with GDM diagnosed by IADPSG criteria; 60 normoglycemic controls) recruited from Al-Imamien Al-Kadhemein Medical City, Baghdad, Iraq, between 5 March and 5 May 2026. Controls were frequency-matched to cases by maternal age, gestational age, and body mass index (BMI). Serum CTRP9 was measured by a sandwich enzyme-linked immunosorbent assay (ELISA). Group comparisons used the independent-samples t-test; discriminatory performance was assessed by receiver operating characteristic (ROC) curve analysis; independent predictive value was assessed by binary logistic regression; and associations were assessed by Spearman correlation and Mann-Whitney U tests. A p-value <0.05 was considered statistically significant.

Results: Serum CTRP9 was significantly higher in the GDM group than in controls (7.692 ± 2.122 vs 6.500 ± 1.998 ng/mL; p = 0.0019). CTRP9 showed modest discriminatory ability for GDM (AUC = 0.677; 95% CI: 0.586–0.760; p = 0.0004), with an optimal cut-off of >7.5 ng/mL (sensitivity 66.67%, specificity 78.33%). In multivariable logistic regression, CTRP9 was not an independent predictor of GDM status (OR = 2.33; 95% CI: 0.82–6.63; p = 0.1127). CTRP9 correlated weakly but significantly with BMI, HbA1c, blood glucose, and birth weight in the total cohort (ρ = 0.18–0.21; p < 0.05), but showed no significant association with gestational hypertension, preeclampsia, preterm delivery, premature rupture of membranes, postpartum hemorrhage, mode of delivery, or NICU admission.

Conclusions: Serum CTRP9 is significantly elevated in GDM and reflects the underlying metabolic burden, but it demonstrates only modest, non-independent diagnostic performance and no association with adverse maternal or neonatal outcomes in this cohort. CTRP9 may therefore represent a disease-associated metabolic marker rather than a predictive or prognostic biomarker of GDM-related complications.