OBJECTIVE: To investigate the significance and relationship of glucose and lipid metabolism, placental resistin, and human lipid carrier protein (LCN-2) expression in pregnant women with gestational diabetes mellitus (GDM) complicated by severe preeclampsia (SPE). METHODS: A total of 89 patients with GDM and SPE (G+S group) and 89 patients with GDM alone (GDM group) were included. Blood samples were collected to measure glucose and lipid metabolism indicators [fasting blood glucose (FBG), fasting insulin (FINS), glycosylated hemoglobin (HbA1c), total cholesterol (TC), triglycerides (TG), HDL-C, and LDL-C], and immunohistochemistry was used to assess placental resistin and LCN-2 levels. Delivery conditions and adverse maternal and neonatal outcomes were compared. Pearson correlation analysis was conducted to explore the relationship between placental resistin, LCN-2, and glucose and lipid metabolism indicators. RESULTS: FBG, FINS, HbA1c, TC, and TG levels were higher, and HDL-C was lower in the G+S group compared to the GDM group (P<
0.05). The positive expression rates of resistin and LCN-2 in placental tissue were also higher in the G+S group (P<
0.05). The G+S group had lower gestational weeks, neonatal birth weight, and higher postpartum hemorrhage than the GDM group (P<
0.05). The G+S group showed higher rates of adverse maternal outcomes (postpartum hemorrhage, intrauterine infection) and neonatal outcomes (preterm birth, fetal distress) (P<
0.05). Pearson analysis showed that placental resistin and LCN-2 expression were positively correlated with FBG, FINS, TC, and TG, and negatively correlated with HDL-C (P<
0.05). CONCLUSION: Pregnant women with GDM and SPE have higher risks of glucose and lipid metabolism disorders, placental resistin and LCN-2 expression, and adverse maternal and neonatal outcomes compared to GDM patients. Resistin and LCN-2 may influence glucose and lipid metabolism, affecting pregnancy outcomes.