Glypican-4 trajectory predicts the risk of gestational diabetes mellitus and the requirement for insulin therapy during pregnancy

• Published in: Frontiers in endocrinology (Lausanne) Vol. 16; p. 1483567
• Main Authors: Tang, Lei, Li, Ping, Li, Ling
• Format: Journal Article
• Language: English
• Published: Switzerland Frontiers Media S.A 21.03.2025
• Subjects: Adult; Biomarkers - blood; Blood Glucose - analysis; Blood Glucose - metabolism; Diabetes, Gestational - blood; Diabetes, Gestational - diagnosis; Diabetes, Gestational - drug therapy; Female; gestational diabetes mellitus; Glucose Tolerance Test; glypican-4; Glypicans - blood; Humans; Hypoglycemic Agents - therapeutic use; Insulin - therapeutic use; insulin therapy; oral glucose tolerance test; postpartum glucose metabolism; Pregnancy; Risk Factors; oral glucose tolerance test; gestational diabetes mellitus; glypican-4; insulin therapy; postpartum glucose metabolism
• ISSN: 1664-2392; 1664-2392
• DOI: 10.3389/fendo.2025.1483567

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. 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 NGT after delivery (NGTd, n = 138) and abnormal glucose tolerance (AGT, n = 20) groups. Glypican-4 level was significantly higher in GDM than NGT subjects during pregnancy ( < 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. 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.