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

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 (P< 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.