Lipoprotein metabolism in gestational diabetes mellitus

The objectives of this dissertation research were to assess the magnitude, potential causes and fetal consequences of alterations in maternal plasma and lipoprotein lipids in GDM. Maternal and cord plasma, very-low density lipoprotein (VLDL), low-density lipoprotein (LDL), high-density lipoprotein (HDL), HDL2 and HDL3 triglyceride (TG), cholesterol (CL), $\alpha$ = tocopherol, retinol, carotenoids, and plasma free fatty acids (FFA), hemoglobin (Hb) A1c and gestational hormones were determined and dietary intake data collected in women with GDM and controls in a longitudinal design. Subjects (n = 25/group) were matched for age, race and body mass index (BMI). Statistical analyses included paired t-tests, repeated measures ANOVA and ANCOVA, and bivariate regression analyses.^ Total energy, fat, CL, vitamins A and E intake were similar between groups. There were no differences between groups or trends over time for plasma or lipoprotein CL, $\alpha$- or $\beta$-carotene, $\alpha$-tocopherol or retinol. Plasma FFA and VLDL, LDL, HDL, HDL2 and HDL3 TG increased with advancing gestation, whereas plasma and HDL lycopene and the hydroxycarotenoids ($\beta$-cryptoxanthin and lutein/zeaxanthin) and LDL lycopene decreased over the third trimester. Subjects with GDM had a higher mean plasma, VLDL, LDL, HDL, HDL2 and HDL3 TG and a lower plasma, VLDL and HDL lycopene and hydroxycarotenoid concentration than controls. There were no significant differences between groups for cord plasma and lipoprotein lipids. Cord plasma retinol, plasma and HDL lutein/zeaxanthin and HDL $\beta$-cryptoxanthin were lower in GDM than controls. HbA1c, plasma progesterone and prolactin were higher throughout the third trimester in GDM and correlated with VLDL, LDL and HDL TG. $\beta$-estradiol was higher in GDM at 37-38 weeks gestation and was correlated with HDL TG. In controls, significant correlations were observed between maternal plasma TG and cord FFA; maternal HDL2 CL and cord plasma CL; and maternal plasma TG, HDL2 CL and infant birth weight. In GDM, maternal plasma CL and cord VLDL + LDL CL were correlated. There were no correlations between maternal or cord lipids and infant birth weight in GDM.^ Thus, maternal hypertriglyceridemia rather than hypercholesterolemia was a feature of GDM. Perturbations in glucose control and gestational hormones in GDM may have contributed to the observed increase in plasma and lipoprotein TG. While exaggerated hyperlipidemia did not contribute to increased lipid transfer to the fetus or macrosomia in women with GDM, lipid perturbations may have contributed to alterations in the antioxidant status (lycopene and the hydroxycarotenoids) of both mother and fetus.