1. Division of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, Madigan Army Medical Center, 9040 Fitzsimmons Drive, Tacoma, WA 98431, USA.
Background: Gestational diabetes mellitus (GDM) complicates 5-6% of pregnancies, placing affected individuals at higher risk for pregnancy-related complications and persistent metabolic and cardiovascular disorders later in life. In this study, we evaluated the association between apolipoproteins and plasma cholesterol levels in patients with gestational diabetes compared to uncomplicated controls over the course of pregnancy.
Methods: Plasma was prospectively collected from 311 nulligravid women during 3 time periods during pregnancy (4-12, 16-22 and 24-28 weeks gestation). Mass spectrometry and enzyme-linked immunosorbant assays (ELISA) were used to measure the relative and absolute changes in apolipoprotein abundance. High density lipoprotein (HDL) and very low/low density lipoprotein (LDL/VLDL) cholesterol levels were quantified by enzymatic assay. Mann Whitney U tests were used to determine statistical significance (p<0.05).
Results: Five cases of GDM were identified (mean 1-hour blood glucose concentration = 163.2 ± 7.3 mg/dL). In the control subjects, plasma concentrations of Apo A-II measured by ELISA marginally increased from 4-12 weeks to 24-28 weeks, while concentrations did not significantly increase in GDM subjects. Likewise, VLDL/LDL cholesterol levels increased in the controls but not in the GDM cohort (p=0.005). HDL cholesterol was not significantly different between cohorts. Mass spectrometry spectral patterns identified Apo A-II dimers, Apo A-II monomers and 3 forms of Apo C-III (asialylated Apo C-III0, monosialylated Apo C-III1 and disialylated Apo C-III2) in patient plasma. In GDM cases, Apo A-II dimers were significantly lower than controls in the second trimester (p<0.05). While both Apo A-II monomer and asialylated Apo C-III0 increased steadily over gestational time in the control subjects (p<0.05), GDM cases showed no statistical change in either protein between trimesters 1, 2 and 3.
Conclusions: The rate of change over gestational time for the apolipoproteins and VLDL/LDL cholesterol was significantly lower in GDM cases than uncomplicated controls, indicating that the normal hyperlipidemia of pregnancy is disrupted in GDM. Our results support a role for impaired lipid transport and homeostasis in GDM and may suggest a potential diagnostic and therapeutic target.
Keywords: Gestational diabetes mellitus, apolipoproteins, cholesterol, lipid, diagnostic