Serum WISP-1 and CTRP1 Levels in Gestational Diabetes Mellitus: Associations with HOMA-IR and Glycemic Status

Background and Objectives: Gestational diabetes mellitus (GDM) is characterized by insulin resistance and metabolic dysregulation, in which adipokines may be involved. We evaluated serum Wnt1-inducible signaling pathway protein-1 (WISP-1/CCN4) and C1q/TNF-related protein-1 (CTRP1) in women with GDM and normal glucose tolerance and assessed their relationships with glucose–insulin homeostasis and cross-sectional discriminatory ability. Materials and Methods: This exploratory cross-sectional biomarker study with prospective obstetric follow-up included 100 pregnant women at 24–28 weeks of gestation (50 GDM and 50 controls). WISP-1, CTRP1, HOMA-IR, and GDM status were assessed during the same gestational period; therefore, the principal biomarker analyses were cross-sectional. GDM was diagnosed using the one-step 75-g oral glucose tolerance test criteria recommended by the American Diabetes Association Standards of Care 2026. WISP-1 and CTRP1 were measured by ELISA. Group comparisons, correlation analyses, ROC analyses, nested logistic regression, and bootstrap internal validation were performed. Results: WISP-1 was higher in GDM than in controls (422.80 [387.10–471.85] vs. 315.00 [288.30–351.55] pg/mL; p < 0.001), as was CTRP1 (34.13 ± 6.74 vs. 26.50 ± 5.65 ng/mL; p < 0.001). WISP-1 showed a higher apparent AUC than CTRP1 in the present cohort (0.908 vs. 0.802; DeLong p = 0.034). In the final model adjusted for maternal age and BMI, both WISP-1 (adjusted OR per 1-SD increase 7.53, 95% CI 2.95–19.21; p < 0.001) and CTRP1 (3.61, 95% CI 1.45–8.99; p = 0.006) remained associated with GDM status after adjustment for these covariates. Within GDM, the age- and BMI-adjusted association between WISP-1 and HOMA-IR remained significant (partial ρ = 0.574; p < 0.001), whereas CTRP1 was not associated with HOMA-IR. Conclusions: WISP-1 and CTRP1 were elevated in GDM, with WISP-1 showing a stronger association with HOMA-IR and a higher internally derived AUC in this cohort. These findings support further investigation of WISP-1 and CTRP1 as exploratory metabolic biomarkers associated with GDM but do not establish diagnostic or predictive utility. Independent external validation is required before any potential clinical application.