Maternal body mass index, birthweight, and placental glucose metabolism: evidence for a role of placental hexokinase

Abstract

BackgroundThe principal fetal energy source is glucose provided by placental transfer of maternal glucose. However, the placenta’s glucose consumption exhibits considerable variation. Hexokinase is the first and one of the rate-limiting enzymes of glycolysis that phosphorylates glucose to glucose 6-phosphate. The role of placental hexokinase activity in human placental glucose metabolism is unknown. ObjectivesTo test the hypothesis that placental hexokinase activity is related to maternal body mass index, placental glucose uptake and consumption, and birth weight. Study designSixty-seven healthy pregnant participants at term were included in this study at Oslo University Hospital, Norway. Placental hexokinase activity was measured by using a colorimetric assay. The mass of glucose taken up by the uteroplacental unit and the fetus was obtained by measuring arterio-venous glucose differences combined with Doppler assessment of uterine and umbilical blood flow. Blood samples were obtained from the maternal radial artery, uterine vein, and umbilical artery and vein. The uteroplacental glucose consumption constituted the difference between uteroplacental and fetal glucose uptake. Spearman’s rank correlation was performed for statistical analyses to study the correlation of placental hexokinase activity (mU/mg protein) with prepregnancy body mass index, maternal glucose and insulin, birth weight, uteroplacental glucose uptake and consumption, and fetal glucose uptake (μmol/min). Partial rank correlation analysis was performed when controlling for hours of fasting or placental weight. ResultsHexokinase activity was detectable in all placental tissue samples. Mean (SD) activity was 19.6 (4.64) mU/mg of protein. Placental hexokinase activity correlated positively with prepregnancy body mass index (Spearman’s rho (ρ)=0.33; P=0.006). Upon controlling for hours of fasting, hexokinase activity showed positive correlations with both maternal glucose (r=0.30; P=0.01) and insulin (r=0.28; P=0.02). Hexokinase activity was positively correlated with uteroplacental glucose uptake (ρ=0.31; P=0.01) and consumption (ρ=0.28; P=0.02). Hexokinase activity did not correlate with fetal glucose uptake. Upon controlling for placental weight, hexokinase activity showed a positive correlation with birth weight (r=0.31; P=0.01). ConclusionOur findings suggest that placental hexokinase, being crucial for uteroplacental retention of glucose for own disposition, is related to both maternal body mass index and birth weight independent of placental weight. Placental hexokinase may play a central role in the relationship between maternal glucose dysregulation and fetal growth. Thus, the current study supports the need to develop clinically useful tools to assess the metabolic properties of the placenta.