Exploring Lactoferrin as a novel marker for disease pathology and ferroptosis regulation in gestational diabetes

Abstract

Iron overload is linked to heightened susceptibility to ferroptosis, a process increasingly implicated in diabetes pathogenesis. This present study aims to assess the utility of Lactoferrin in predicting different stages of GDM and explore its association with disease pathology and ferroptosis. In this observational study, 72 pregnant women were recruited and categorized into three groups: healthy pregnant women without diabetes (NGDM, n = 24), early gestational diabetes (eGDM, n = 24), and established gestational diabetes (GDM, n = 24), all receiving standard antenatal care at 12 weeks of gestation. Circulating levels of ferritin, soluble transferrin receptor (sTFR), and Lactoferrin using multiplexed bead-based cytokine immunoassay. Gene expression analysis focused on analyzing crucial ferroptosis regulators, SLC7A11 and GPX4, in isolated peripheral blood mononuclear cells (PBMCs). A significant elevation in ferritin levels and a decrease in the sTFR: Ferritin ratio supported iron overload and disrupted iron homeostasis in GDM subjects. Notably, Lactoferrin levels were significantly lower in women with GDM than in the control group and those with eGDM. This decline in Lactoferrin correlated with increased hyperglycemia indicators and reduced expression of ferroptosis regulators among GDM patients. Furthermore ROC curve analysis demonstrated that Lactoferrin shows promise as a valuable marker for distinguishing individuals with GDM from those with eGDM. Lactoferrin shows promise as a biomarker for detecting GDM. These findings indicate its role as a potential biomarker and highlight Lactoferrin as a critical regulator of hyperglycemia and ferroptosis in women with GDM.

Keywords: Ferritin; Ferroptosis; Gestational diabetes; Lactoferrin; Pregnancy.