The Clinical Diagnostic Value of Serum Exosomal Proteins PAPP-A and CAMK2β in Gestational Diabetes Mellitus

Abstract This study evaluates the potential of exosomal proteins pregnancy-associated plasma protein-A (PAPP-A) and calcium/calmodulin-dependent protein kinase 2β (CAMK2β) as early diagnostic biomarkers for gestational diabetes mellitus (GDM) and investigates their roles and associated signaling pathways in GDM. Serum exosomes from serum were analyzed for protein levels of PAPP-A and CAMK2β, correlating with metabolic indicators and pregnancy outcomes. Diagnostic accuracy was assessed using ROC curves, with AUC values of 0.843 for PAPP-A and 0.895 for CAMK2β, indicating high diagnostic potential. Despite distinct expression patterns in GDM patients compared to healthy pregnant women with PAPP-A linked to early pregnancy BMI and lipid levels, while CAMK2β showed an inverse trend, neither protein significantly correlated with delivery outcomes, suggesting the need for further exploration into their roles in GDM pathogenesis bioinformatics analysis revealed that PAPP-A is involved in insulin-like growth factors (IGFs), growth factor (GFs) signaling, glucose metabolic processes, and the MAPK pathway, while CAMK2β is associated with intracellular calcium signaling and ion transport. These findings highlight the multifaceted regulatory roles of PAPP-A and CAMK2β in metabolic diseases and biological processes relevant to GDM. Our results position these serum exosomal proteins as promising early GDM biomarkers, offering new insights for clinical diagnosis and potentially guiding prevention and treatment strategies.