Elevated serum squalene and cholesterol synthesis markers in pregnant obese women with gestational diabetes mellitus

Abstract

We examined serum cholesterol synthesis and absorption markers and their association with neonatal birth weight in obese pregnancies affected by gestational diabetes mellitus (GDM). Pregnant women at risk for GDM (BMI >30 kg/m²) were enrolled from maternity clinics in Finland. GDM was determined from the results of an oral glucose tolerance test. Serum samples were collected at six time-points, one in each trimester of pregnancy, and at 6 weeks, 6 months, and 12 months postpartum. Analysis of serum squalene and noncholesterol sterols by gas-liquid chromatography revealed that in subjects with GDM (n = 22), the serum Δ8-cholestenol concentration and lathosterol/sitosterol ratio were higher (P < 0.05) than in the controls (n = 30) in the first trimester, reflecting increased cholesterol synthesis. Also, subjects with GDM had an increased ratio of squalene to cholesterol (100 × μmol/mmol of cholesterol) in the second (11.5 ± 0.5 vs. 9.1 ± 0.5, P < 0.01) and third (12.1 ± 0.8 vs. 10.0 ± 0.7, P < 0.05) trimester. In GDM, the second trimester maternal serum squalene concentration correlated with neonatal birth weight (r = 0.70, P < 0.001). In conclusion, in obesity, GDM associated with elevated serum markers of cholesterol synthesis. Correlation of maternal serum squalene with neonatal birth weight suggests a potential contribution of maternal cholesterol synthesis to newborn weight in GDM.

Trial registration: ClinicalTrials.gov NCT01698385.

Keywords: cholestanol; cholesterol metabolism• fetal weight; glucose; insulin; lipoprotein; obesity; phospholipid.

Copyright © 2014 by the American Society for Biochemistry and Molecular Biology, Inc.

Figures

Fig. 1.

The ratios of serum squalene and noncholesterol sterols to cholesterol (100 × μmol/mmol of cholesterol) in I, II, and III trimester of pregnancy, and 6 weeks, 6 months, and 12 months postpartum (p.p.) in control subjects (open circles) and subjects with GDM (filled circles). Values are mean ± SE. *P < 0.05, controls versus GDM. GLM adjusted for BMI.

Fig. 2.

Correlation between neonatal birth weight (g) and maternal serum squalene concentration (μg/dl) in the second trimester of control pregnancies (n = 30) (A) and pregnancies affected by GDM (n = 22) (B).