Impaired lipid transport in gestational diabetes mellitus

Abstract

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-III 0 , monosialylated Apo C-III 1 and disialylated Apo C-III 2 ) 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-III 0 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.

Identification of candidate biomarkers for the prediction of gestational diabetes mellitus in the early stages of pregnancy using iTRAQ quantitative proteomics

“…Apolipoprotein CIII was identified as candidate biomarkers in the maternal circulation at 16 to 20 wk in women with subsequently developed GDM . Plasma concentrations of Apo A‐II were observed to be increased from 4–12 wk to 24–28 wk in GDM patients . Two apolipoproteins (apos), APOA5 and APOE, were found to be increased in women with subsequently developed GDM in this study, supporting the view that impaired lipid transport and homeostasis play a role in GDM.…”

“…Most of them include blood coagulation, inflammatory response, immune response, complement activation, oxidative stress, etc. Interestingly, these processes have previously been linked to the pathophysiology of GDM , and thus the proteins can be considered as candidate biomarkers for screening and diagnosis of GDM.…”

Comparative Proteomics Analysis of Serum Proteins in Gestational Diabetes during Early and Middle Stages of Pregnancy

“…Moreover, the levels of three proteins, that is, APOA5, APOE, and PON1 and the other three proteins (APOC3, APOE, and PON1) associated with cholesterol efflux were found to be significantly higher in the serum of pregnant women who subsequently developed GDM and pregnant women with GDM, respectively. Previous studies showed that APO A‐II, APOC3, APOA5, APOE, and PON1 might serve as candidate biomarkers of GDM. These results support a role for impaired lipid transport in GDM and suggest a potential prediction and diagnosis of GDM.…”

Proteomics Analysis of Serum Proteins in Gestational Diabetes

“…Studies have shown that in patients with poorly controlled GDM, higher concentrations of high-density lipoproteins and higher triglyceride levels were detected in the third trimester, and the second and third trimesters, respectively. Another study suggested that APOA-II, APOC3 [19], APOE and PON1 [9] might be candidate biomarkers for GDM. Consistent with the above studies, we observed signi cantly higher levels of apolipoproteins APOE and APOC3 in the serum of GDM pregnant women.…”