Kilby M D, Neary R H, Mackness M I, Durrington P N
Department of Fetal Medicine, Birmingham Womens Hospital, University of Birmingham, United Kingdom.
J Clin Endocrinol Metab. 1998 May;83(5):1736-41. doi: 10.1210/jcem.83.5.4783.
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.
对10例单胎足月妊娠且孕前患有胰岛素依赖型糖尿病（I型糖尿病）的孕妇及22例非糖尿病孕妇，在择期剖宫产分娩时测定其母血和脐静脉血中的血脂、载脂蛋白浓度及脂蛋白组成。本研究的目的是确定母亲I型糖尿病的影响，以及由此产生的潜在胎儿营养过剩对胎儿脂质代谢的影响。I型糖尿病组与非糖尿病妊娠组在孕周、胎儿体重或胎儿血清胰岛素浓度方面无显著差异，尽管胎儿脐静脉血糖分别为3.4 mmol/L（3.0 - 4.5 mmol/L）（中位数和第25 - 75百分位数）和2.9 mmol/L（2.0 - 3.4 mmol/L），且母亲糖化血红蛋白A1c分别为[9.6%（8.2 - 10.7%）和6.8%（6.3 - 7.8%）]，I型糖尿病患者显著更高（分别为P < 0.02和0.002）。I型糖尿病母亲的血浆非酯化脂肪酸（NEFA）浓度较低[0.85 mmol/L（0.56 - 2.31 mmol/L），而在非糖尿病妊娠中为1.14 mmol/L（0.88 - 1.24 mmol/L）；P < 0.0001]。I型糖尿病母亲的血清高密度脂蛋白磷脂（HDL - PL）因HDL2磷脂升高而增加[分别为0.39 mmol/L（0.27 - 0.48 mmol/L）和0.12 mmol/L（0.06 - 0.21 mmol/L），P < 0.01]。在未合并症和I型糖尿病妊娠中，母亲的HDL胆固醇（C）浓度无显著差异。然而，在脐静脉血中，NEFA的血清水平[I型糖尿病中为0.49 mmol/L（0.33 - 1.29 mmol/L），非糖尿病患者为0.13 mmol/L（0.06 - 0.33 mmol/L）；P < 0.02]、总胆固醇（TC）[I型糖尿病中为2.87 mmol/L（1.65 - 4.86 mmol/L），非糖尿病患者为1.65 mmol/L（1.46 - 1.87 mmol/L）；P < 0.02]、游离胆固醇（FC）[I型糖尿病中为0.97 mmol/L（0.60 - 1.26 mmol/L），非糖尿病患者为0.62 mmol/L（0.37 - 0.75 mmol/L）；P < 0.05]、胆固醇酯（CE）[I型糖尿病中为1.90 mmol/L（1.44 - 3.33 mmol/L），非糖尿病患者为1.01 mmol/L（0.83 - 1.24 mmol/L）；P < 0.02]、甘油三酯（TG）[I型糖尿病中为1.06 [0.50 - 1.91] mmol/L，非糖尿病患者为0.29 [0.25 - 0.36] mmol/L；P < 0.001]、磷脂（PL）[I型糖尿病中为2.52 [1.73 - 3.03] mmol/L，非糖尿病患者为1.34 [1.27 - 1.48] mmol/L；P < 0.01]，以及载脂蛋白A - I和B在I型糖尿病中的浓度显著更高。在脐静脉血中，当母亲孕期患有I型糖尿病时，反映HDL脂质含量的HDL - TC和HDL - PL与载脂蛋白AI的比值降低（分别为P < 0.02和P < 0.0001）。这些结果表明，母亲I型糖尿病可能导致胎儿血清脂蛋白组成更类似于成人。在I型糖尿病中，母亲的TG和PL以及胎儿的TC、TG、PL、CE和FC与NEFA水平相关（P < 0.05），但与葡萄糖、胰岛素分泌或母亲I型糖尿病的控制无关。这些数据表明，I型糖尿病妊娠中胎儿NEFA供应的增加可能驱动胆固醇以及TG和PL的合成。
