The Rising Concern: Gestational DiabetesGestational diabetes mellitus (GDM) is a growing public health concern, especially in Asia, with prevalence rates nearing 15%. This metabolic complication during pregnancy not only increases the risk of birth complications but also raises the long-term risk of diabetes, obesity, and cardiovascular disease for both mother and child. Early prediction and prevention are vital, but which biomarkers can really provide the answers?IGF-I and Osteocalcin: More Than Just HormonesInsulin-like growth factor-I (IGF-I) and osteocalcin (OC)—particularly its undercarboxylated form (ucOC)—have recently gained attention for their roles in glucose metabolism. IGF-I is known to affect insulin sensitivity and glucose homeostasis, while ucOC, a bone-derived hormone, is implicated in regulating pancreatic β-cell function and insulin secretion. Yet, their precise relationship with GDM has remained unclear.The Study: Putting the Link to the TestIn a recently published research, Cui et al. conducted a case-control study involving 125 Chinese women with GDM and 153 healthy pregnant controls, all in their second trimester. By measuring serum levels of IGF-I, OC, and ucOC, and using advanced statistical modeling, the researchers assessed how these markers relate to GDM risk. The analysis also explored whether ucOC acts as a mediator in the IGF-I–GDM association.Key Findings: • Both higher IGF-I and ucOC levels were significantly associated with increased GDM risk. • The association between IGF-I and GDM was non-linear, with risk rising sharply at IGF-I concentrations above 3.83 ng/mL. • Mediation analysis revealed that nearly half (48.6%) of IGF-I’s impact on GDM risk may be explained by ucOC. • A predictive model combining IGF-I, ucOC, and OC improved the accuracy of GDM risk prediction, with an area under the ROC curve (AUC) of 76.2%.Clinical Implications: Toward Better Prediction and PreventionThe study’s findings suggest that monitoring IGF-I and ucOC levels in mid-pregnancy could offer a new dimension for early GDM screening and risk stratification. Since ucOC mediates a substantial part of IGF-I’s effect on GDM risk, both markers could potentially become targets for clinical interventions or future therapeutic strategies.Key Takeaways: • Elevated IGF-I and ucOC levels are strong predictors of gestational diabetes risk. • The relationship between IGF-I and GDM is non-linear and mediated by ucOC. • Combining IGF-I, OC, and ucOC measurements enhances predictive accuracy for GDM. • Early biochemical screening could transform management and prevention of GDM.Citation: Cui L., Gao Y., Sun R., Li Z., Zhang Z., Ji L., Wang Y., Ye H., Qin L. (2025). Mediating effect of osteocalcin underlying the link between insulin-like growth factor-I and gestational diabetes mellitus. BMC Pregnancy and Childbirth, 25:579. https://doi.org/10.1186/s12884-025-07689-8