Abstract Background Gestational diabetes mellitus (GDM) is a growing global epidemic. Our study aims to confirm the association between circulatory coiled-coil domain-containing 80 (CCDC80) in pregnant women with GDM, to investigate the discriminatory power of CCDC80 on GDM, and to explore the relationships between this molecular level and clinical cardiometabolic parameters. Methods A 1:2 matched case-control study with 61 GDM patients and 122 controls was conducted using a propensity score matching protocol. All participants were screened from a multicenter prospective pre-birth cohort: Born in Shenyang Cohort Study (BISCS). During 24 and 28 weeks of gestation, follow-up individuals underwent an oral glucose tolerance test (OGTT) and blood sampling for cardiometabolic characterization. Results Following propensity score matching adjustment for clinical variables, including maternal age, gestational age, body mass index, SBP and DBP, plasma CCDC80 levels were significantly decreased in patients with GDM when...