Increased glucose and placental GLUT-1 in large infants of obese nondiabetic mothers

Abstract

Obese women are at increased risk to deliver a large infant, however, the underlying mechanisms are poorly understood. Fetal glucose availability is critically dependent on placental transfer and is linked to fetal growth by regulating the release of fetal growth hormones such as insulin. We hypothesized that (1) umbilical vein glucose and insulin levels and (2) placental glucose transporter (GLUT) expression and activity are positively correlated with early pregnancy maternal body mass index and infant birthweight. Subjects in this prospective observational cohort study were nondiabetic predominantly Hispanic women delivered at term. Fasting maternal and umbilical vein glucose and insulin concentrations were determined in 29 women with varying early pregnancy body mass index (range, 18.0-54.3) who delivered infants with birthweights ranging from 2800-4402 g. We isolated syncytiotrophoblast microvillous and basal plasma membranes from 33 placentas and determined the expression of GLUT-1 and -9 (Western blot) and glucose uptake (radiolabeled glucose). Birthweight was positively correlated with umbilical vein glucose and insulin and maternal body mass index. Umbilical vein glucose levels were positively correlated with placental weight and maternal body mass index, but not with maternal fasting glucose. Basal plasma membranes GLUT-1 expression was positively correlated with birthweight. In contrast, syncytiotrophoblast microvillous GLUT-1 and -9, basal plasma membranes GLUT-9 expression and syncytiotrophoblast microvillous and basal plasma membranes glucose transport activity were not correlated with birthweight. Because maternal fasting glucose levels and placental glucose transport capacity were not increased in obese women delivering larger infants, we speculate that increased placental size promotes glucose delivery to these fetuses.