Gestational diabetes mellitus-induced adipokine dysregulation and links to metabolic programming risks

Gestational diabetes mellitus (GDM) is a pregnancy-related hyperglycemic disorder with highly variable global prevalence, largely driven by differences in diagnostic criteria, maternal characteristics, and lifestyle factors, which complicates efforts to standardize screening and prevention. GDM disrupts maternal-fetal glucose homeostasis, leading to fetal exposure to hyperglycemia and hyperinsulinemia, and is associated not only with immediate obstetric complications but also with long-term metabolic risk in both mothers and offspring.

This study evaluated the impact of maternal hyperglycemia, classified as diet-controlled (GDM-diet) or insulin-treated (GDM-insulin), on leptin, adiponectin, soluble leptin receptor (sLeptinR), and the derived indices leptin-to-adiponectin ratio (LAR) and free leptin index (FLI) across the maternal-fetal axis.

This study was a retrospective observational cohort study targeting patients with gestational diabetes mellitus. Maternal and cord blood plasma from 30 hyperglycemic and 23 normoglycemic mothers were analyzed for leptin, adiponectin, and soluble leptin receptor concentrations using immunoenzymatic assays.

Maternal plasma leptin concentrations were significantly higher in the GDM-insulin group (10.05 ng/mL) than in non-GDM pregnancies (4.44 ng/mL; p = 0.033). The leptin-to-adiponectin ratio was also elevated in GDM-insulin (4.99) compared to GDM-diet (2.18; p = 0.043). No significant between-group differences were observed for adiponectin, soluble leptin receptor, or the free leptin index. In cord blood, adiponectin concentrations were higher in GDM-diet neonates (9.05 μg/mL) than in GDM-insulin (5.70 μg/mL; p = 0.010). Maternal leptin and its derived indices (LAR, FLI) were associated with maternal overweight/obesity, whereas maternal adiponectin and cord blood leptin were related to neonatal birth weight.

These findings point to leptin, adiponectin, FLI, and LAR as possible metabolic indicators of GDM-linked insulin resistance, and low-grade inflammation. Higher maternal leptin, LAR, and FLI, alongside stable sLeptinR, signal leptin resistance, which disrupts placental nutrient transport and links maternal metabolic stress to fetal anthropometric measures. Tracking these markers could guide postnatal steps to cut long-term metabolic risks across the next generations.