Placental and maternal sFlt1/PlGF expression in gestational diabetes mellitus

Abstract

Gestational diabetes mellitus (GDM) and preeclampsia (PE) are both characterized by endothelial dysfunction and GDM women have higher incidence of PE. The placenta plays a key role in PE pathogenesis but its contribution to PE during GDM remains unclear. Herein, we compared placental and maternal blood anti-angiogenic soluble fms-like tyrosine kinase-1 (sFlt1) and pro-angiogenic Placental Growth Factor (PlGF) expressions in GDM and GDM-PE pregnancies compared to controls (CTRL) and PE cases. Electrochemiluminescence immunoassays showed a significantly higher maternal blood sFlt1/PlGF values in GDM-PE relative to CTRL and GDM pregnancies. We reported that placental PlGF gene expression was significantly decreased in GDM, PE and GDM-PE relative to CTRL. However, PlGF protein levels were significantly increased in GDM and GDM-PE relative to CTRL and PE placentae. Finally, sFlt1 gene expression was significantly increased in PE relative to CTRL, GDM and GDM-PE placentae. In contrast, sFlt1 protein expression was significantly decreased in GDM-PE relative to CTRL, GDM and PE placentae. Finally, higher sFlt1/PlGF ratio in GDM-PE maternal blood suggest that sFlt1 overproduction is related to PE onset also in GDM pregnancies even though characterized by a less severe endothelial dysfunction in terms of angiogenic biomarkers.

Early markers of gestational diabetes mellitus

“…A more recent study involving PIGF is by Gorkem et al and, although it included 158 pregnant women and showed elevated serum PIGF values in pregnant women with GDM, study was done between 24 and 28 week of gestation and does not provide information whether PIGF is reliable early marker ( 97 ). Recently published small clinical study by Nuzzo et al showed no difference between PIGF, soluble fms-like tyrosine kinase 1 (sFlt1) and sFlt1/PIGF ratio between GDM pregnant women and healthy ones ( 98 ).…”

Placental Glucose Transporters and Response to Bisphenol A in Pregnancies from of Normal and Overweight Mothers

“…GDM diagnosis was performed as previously described by Nuzzo et al [ 52 ]. Briefly, the oral glucose tolerance test (OGTT) was performed by administrating 75 g of glucose between 16 and 18 weeks of gestation in women with at least one high-risk factor.…”

“…In the case of normal OGTT results, the test was repeated at 24–28 weeks of gestation. Women with one or more plasma glucose values above the established thresholds (≥92 mg/dL at baseline, ≥180 mg/dL after 1 h from load, ≥153 mg/Dl after 2 h from load) were diagnosed as GDM [ 52 ]. In our cohort, all the GDM patients routinely received dietary counseling and nutritional recommendations in line with guidelines [ 53 ].…”

Periodontitis and Gestational Diabetes Mellitus: A Potential Inflammatory Vicious Cycle

“…Other placental hormones contribute to physiologic insulin resistance during normal pregnancies, but when the pancreatic compensatory insulin production is altered, as it is in GDM, they may end up contributing to GDM development. For instance, hPL in normal pregnancies enhances pancreatic insulin production when it binds its receptor in pancreatic beta cells through pancreatic and duodenal homeobox 1(PDX1) expression [54], although it has also been reported to act as an insulin antagonist [55,56], and mouse models lack the early expression of receptors for hPL generate obesity, hyperleptinemia and glucose intolerance [57]. Likewise, PLGF overexpression generates fasting and postprandial hyperinsulinemia with low glycemia reduction after insulin injection in transgenic mice [56].…”

“…Likewise, PLGF overexpression generates fasting and postprandial hyperinsulinemia with low glycemia reduction after insulin injection in transgenic mice [56]. That aside, PLGF protein expression is significantly higher in GDM placentas when compared with healthy controls [55].…”