{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,27]],"date-time":"2026-03-27T17:16:12Z","timestamp":1774631772047,"version":"3.50.1"},"reference-count":32,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,3,21]],"date-time":"2025-03-21T00:00:00Z","timestamp":1742515200000},"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>Background<\/jats:title><jats:p>Gestational diabetes mellitus (GDM), characterized by the onset of glucose intolerance during pregnancy, results in a series of complications for maternal and fetal health. Oral glucose tolerance test (OGTT) for screening glucose metabolism is performed in mid-to-late pregnancy, which remains less time to optimize glycemic control. Glypican-4, an insulin-sensitive adipose hormone, exhibits correlations with metabolic indicators. This study aims to investigate the association between glypican-4 and the risk of developing GDM, as well as the effects on insulin therapy and postpartum glucose metabolism.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Based on pregnancy 75-g OGTT results, 718 subjects were grouped into normal glucose tolerance (NGT, n = 345) and GDM (n = 373) groups. 373 GDM patients were divided into the diet (n = 237) and insulin (n = 136) groups according to the treatment of hyperglycemia in pregnancy. Based on postpartum 75-g OGTT results, 158 of the 373 GDM patients were further divided into the\u00a0NGT after delivery (NGTd, n = 138) and abnormal glucose tolerance (AGT, n = 20) groups.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Glypican-4 level was significantly higher in GDM than NGT subjects during pregnancy (<jats:italic>P<\/jats:italic>&amp;lt; 0.001). Glypican-4 was an independent predictor of GDM with the cut-offs were 0.40 ng\/mL (5-12 weeks of gestation) and 0.79 ng\/mL (13-23 weeks of gestation). Furthermore, glypican-4 level in the insulin group was higher than the diet group, which was a potential predictor of insulin therapy.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Glypican-4 during pregnancy is associated with GDM risk, with higher levels indicating increased risk. Glypican-4 was also related to insulin therapy in GDM.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fendo.2025.1483567","type":"journal-article","created":{"date-parts":[[2025,3,21]],"date-time":"2025-03-21T05:30:42Z","timestamp":1742535042000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Glypican-4 trajectory predicts the risk of gestational diabetes mellitus and the requirement for insulin therapy during pregnancy"],"prefix":"10.3389","volume":"16","author":[{"given":"Lei","family":"Tang","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ping","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ling","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2025,3,21]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1016\/j.diabres.2021.109050","article-title":"IDF diabetes atlas: estimation of global and regional gestational diabetes mellitus prevalence for 2021 by international association of diabetes in pregnancy study group\u2019s criteria","volume":"183","author":"Wang","year":"2022","journal-title":"Diabetes Res Clin Pract"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1001\/jama.286.20.2516","article-title":"Gestational diabetes mellitus","volume":"286","author":"Jovanovic","year":"2001","journal-title":"JAMA."},{"key":"B3","doi-asserted-by":"publisher","first-page":"1991","DOI":"10.1056\/NEJMoa0707943","article-title":"Hyperglycemia and adverse pregnancy outcomes","volume":"358","author":"Metzger","year":"2008","journal-title":"N Engl J Med"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.2337\/dc18-1646","article-title":"Hyperglycemia and adverse pregnancy outcome follow-up study (HAPO FUS): maternal gestational diabetes mellitus and childhood glucose metabolism","volume":"42","author":"Lowe","year":"2019","journal-title":"Diabetes Care"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2022.3189","article-title":"Risk of adverse pregnancy outcomes among pregnant individuals with gestational diabetes by race and ethnicity in the United States, 2014-2020","volume":"327","author":"Venkatesh","year":"2022","journal-title":"JAMA."},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.2337\/dc22-S015","article-title":"15. 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