FETAL AND MATERNAL LIPOPROTEIN METABOLISM IN HUMAN-PREGNANCY COMPLICATED BY TYPE-I DIABETES-MELLITUS

Serum lipid, apolipoprotein concentration, and lipoprotein composition were determined in maternal and umbilical venous cord blood at delive ry by elective Cesarean section (CS) in 10 singleton, full-term pregna ncies with maternal insulin-dependent diabetes mellitus (type I DM), w hich predated pregnancy, and in 22 nondiabetic pregnancies. The object ives of the study were to determine the influence of maternal type I D M, 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 percenti les) and 2.9 mmol/L (2.0-3.4 mmol/L), respectively, and maternal Hemog lobin Alc [9.6% (8.2-10.7%) and 6.8% (6.3-7.8%), respectively], was si gnificantly greater in the type I DM subjects (P < 0.02 and 0.002 resp ectively). Plasma nonesterified fatty acid (NEFA) concentrations were lower in the type I DM mothers [0.85 mmol/L (0.56-2.31 mmol/L) compare d 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 in creased in type I DM mothers because of elevated HDL, 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) concent ration was not significantly different in the uncomplicated and type I DM pregnancies. However, in the umbilical venous cord blood, serum le vels of NEFA [0.49 mmol/L (0.33-1.29 mmol/L) in type I DM compared wit h 0.13 mmol/L (0.06-0.33 mmol/L) in nondiabetics; P < 0.02)],total cho lesterol(TC) [2.87 mmol/L (1.65-4.86 mmol/L) in type I DM compared wit h 1.65 mmol/L (1.46-1.87 mmol/L) in nondiabetics; P < 0.02], free chol esterol (FC) [0.97 mmol/L (0.60-1.26 mmol/L) in type I DM compared wit h 0.62 mmol/L (0.37-0.75 mmol/L) in nondiabetics; P < 0.05), and chole steryl ester (CE) [1.90 mmol/L (1.44-3.33 mmol/L) in type I DM compare d with 1.01 mmol/L (0.83-1.24 mmol/L) in nondiabetics; P < 0.02), trig lyceride (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 s ignificantly higher concentrations in type I DM. In umbilical venous c ord 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 pre gnancy (P < 0.02 and P < 0.0001, respectively). These results indicate that maternal type I DM may lead to a fetal serum lipoprotein composi tion more closely resembling that seen in the adult. In type I DM, mat ernal TG and PL and fetal TC, TG, PL CE, and FC were correlated to NEF A levels (P < 0.05), but not to glucose, insulin secretion, or materna l 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.