Fetal and maternal lipoprotein metabolism in human pregnancy complicated by type I diabetes mellitus

Abstract

Serum lipid, apolipoprotein concentration, and lipoprotein composition were determined in maternal and umbilical venous cord blood at delivery by elective Cesarean section (CS) in 10 singleton, full-term pregnancies with maternal insulin-dependent diabetes mellitus (type I DM), which predated pregnancy, and in 22 nondiabetic pregnancies. The objectives of the study were to determine the influence of maternal type I DM, and hence potential fetal overnutrition on fetal lipid metabolism. There were no significant differences in gestational age, fetal weight, or fetal serum insulin concentration between the type I DM group and those with nondiabetic pregnancies, although fetal venous cord blood glucose was 3.4 mmol/L (3.0-4.5 mmol/L) (median and 25th-75th percentiles) and 2.9 mmol/L (2.0-3.4 mmol/L), respectively, and maternal Hemoglobin A1c [9.6% (8.2-10.7%) and 6.8% (6.3-7.8%), respectively], was significantly greater in the type I DM subjects (P < 0.02 and 0.002 respectively). Plasma nonesterified fatty acid (NEFA) concentrations were lower in the type I DM mothers [0.85 mmol/L (0.56-2.31 mmol/L) compared with 1.14 mmol/L (0.88-1.24 mmol/L] in nondiabetic pregnancies; P < 0.0001). Serum high-density lipoprotein phospholipids (HDL-PL) were increased in type I DM mothers because of elevated HDL2 phospholipid [0.39 mmol/L (0.27-0.48 mmol/L) compared with 0.12 mmol/L (0.06-0.21 mmol/L), respectively, P < 0.01). The maternal HDL cholesterol (C) concentration was not significantly different in the uncomplicated and type I DM pregnancies. However, in the umbilical venous cord blood, serum levels of NEFA [0.49 mmol/L (0.33-1.29 mmol/L) in type I DM compared with 0.13 mmol/L (0.06-0.33 mmol/L) in nondiabetics; P < 0.02)], total cholesterol (TC) [2.87 mmol/L (1.65-4.86 mmol/L) in type I DM compared with 1.65 mmol/L (1.46-1.87 mmol/L) in nondiabetics; P < 0.02]; free cholesterol (FC) [0.97 mmol/L (0.60-1.26 mmol/L) in type I DM compared with 0.62 mmol/L (0.37-0.75 mmol/L) in nondiabetics; P < 0.05), and cholesteryl ester (CE) [1.90 mmol/L (1.44-3.33 mmol/L) in type I DM compared with 1.01 mmol/L (0.83-1.24 mmol/L) in nondiabetics; P < 0.02), triglyceride (TG) (1.06 [0.50-1.91) mmol/L in type I DM compared with 0.29 [0.25-0.36] mmol/l in nondiabetics; P < 0.001), phospholipid (PL) (2.52 [1.73-3.03) mmol/L in type I DM compared with 1.34 [1.27-1.48] mmol/L in nondiabetics; P < 0.01], and the apolipoproteins A-I and B had significantly higher concentrations in type I DM. In umbilical venous cord blood, ratios of HDL-TC and HDL-PL to apo AI, reflecting the lipid content of HDL, were reduced when the mother had type I DM during pregnancy (P < 0.02 and P < 0.0001, respectively). These results indicate that maternal type I DM may lead to a fetal serum lipoprotein composition more closely resembling that seen in the adult. In type I DM, maternal TG and PL and fetal TC, TG, PL, CE, and FC were correlated to NEFA levels (P < 0.05), but not to glucose, insulin secretion, or maternal control of type I DM. These data suggest that the enhanced supply of NEFA to the fetus in type I DM pregnancies may drive the synthesis of cholesterol as well as TGs and PLs.