{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,2]],"date-time":"2026-03-02T12:48:24Z","timestamp":1772455704000,"version":"3.50.1"},"reference-count":30,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,9,2]],"date-time":"2025-09-02T00:00:00Z","timestamp":1756771200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Endocrinol."],"abstract":"<jats:sec><jats:title>Objectives<\/jats:title><jats:p>Gestational diabetes mellitus (GDM) is a metabolic disorder that increases the risk of premature rupture of membranes (PROM). The link between GDM-associated metabolic dysregulation and PROM remains unclear. This study investigates the underlying metabolic mechanisms to identify potential therapeutic targets for improving pregnancy outcomes.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>The study involved 354 mothers from the GDM Mother and Child Study (GMCS) at Wuxi People\u2019s Hospital, Nanjing Medical University. A regression model assessed the GDM-PROM relationship. Third-trimester serum metabolites were analyzed using ultra-high-performance liquid chromatography and high-resolution mass spectrometry.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>A higher percentage of women with PROM were diagnosed with GDM (15.7% vs. 32.3%, P=0.005). Although no significant differences were found in 1-h and 2-h glucose levels (P=0.216 and 0.129), fasting glucose was elevated in the PROM group (4.50 [0.43] vs. 4.73 [0.71], P=0.017). Both unadjusted and adjusted models confirmed GDM as a risk factor for PROM (OR: 2.548, 95% CI: 1.341\u20134.759; P=0.004). After adjusting for confounders, GDM remained positively associated with PROM risk (OR: 2.538, 95% CI: 1.223\u20135.224; P=0.012). Hydroxydesmethylpiperine sulfate levels were significantly elevated in all study groups.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>GDM elevates PROM risk by disrupting fetal membrane integrity through metabolic alterations. Elevated hydroxydesmethylpiperine sulfate levels in GDM-PROM cases indicate its potential as a PROM risk biomarker, underscoring the importance of early metabolic screening and glycemic control. Further research should explore this metabolite\u2019s mechanisms and therapeutic potential.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fendo.2025.1631638","type":"journal-article","created":{"date-parts":[[2025,9,2]],"date-time":"2025-09-02T04:11:13Z","timestamp":1756786273000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["Gestational diabetes increases preterm membrane rupture risk through elevated hydroxydesmethylpiperine sulfate 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