Effects of Gestational Diabetes Mellitus on Cholesterol Metabolism in Women with High-Risk Pregnancies: Possible Implications for Neonatal Outcome

Abstract

Metabolic disorders in pregnancy, particularly gestational diabetes mellitus (GDM), are associated with an increased risk for adverse pregnancy outcome and long-term cardiometabolic health of mother and child. This study analyzed changes of serum cholesterol synthesis and absorption markers during the course of high-risk pregnancies, with respect to the development of GDM. Possible associations of maternal lipid biomarkers with neonatal characteristics were also investigated. The study included 63 women with high risk for development of pregnancy complications. Size and proportions of small low-density (LDL) and high-density lipoprotein (HDL) particles were assessed across trimesters (T1–T3), as well as concentrations of cholesterol synthesis (lathosterol, desmosterol) and absorption markers (campesterol, β-sitosterol). During the study, 15 women developed GDM, while 48 had no complications (non-GDM). As compared to the non-GDM group, women with GDM had significantly higher triglycerides in each trimester, while having a lower HDL-C level in T3. In addition, they had significantly lower levels of β-sitosterol in T3 (p < 0.05). Cholesterol synthesis markers increased across trimesters in both groups. A decrease in serum β-sitosterol levels during the course of pregnancies affected by GDM was observed. The prevalence of small-sized HDL decreased in non-GDM, while in the GDM group remained unchanged across trimesters. Newborn’s size in the non-GDM group was significantly higher (p < 0.01) and inversely associated with proportions of both small, dense LDL and HDL particles (p < 0.05) in maternal plasma in T1. In conclusion, high-risk pregnancies affected by GDM are characterized by altered cholesterol absorption and HDL maturation. Advanced lipid testing may indicate disturbed lipid homeostasis in GDM.

Oxidative Stress, Atherogenic Dyslipidemia, and Cardiovascular Risk

“…Circulatory endogenous precursors of cholesterol can be used as markers of cholesterol synthesis, while phytosterols, which use the same absorption route as cholesterol, are proposed as cholesterol absorption markers (Figure 4) [122]. Cholesterol synthesis and absorption are reciprocally regulated in healthy individuals, but it has been demonstrated that various pathological states are characterized by the disturbance of the balance between these processes [123][124][125][126][127][128][129][130]. Accordingly, non-cholesterol sterols could be used, not only as indicators of altered cholesterol homeostasis, but also as markers of several diseases, including CVD, and predictors of therapeutic response.…”

The relevance of cholesterol and triglycerides in pregnancy

“…Dyslipidemia in pregnancy is associated with gestational diabetes mellitus (GDM), preeclampsia, macrosomia, preterm birth, and other pregnancy complications. Women with a rich-in-cholesterol diet have a higher incidence of developing gestational diabetes (15). A low level of HDL-C and an elevated BMI have a particular impact on the development of GDM (13).…”