Plasma Ceramide Concentrations in Full-Term Pregnancies Complicated with Gestational Diabetes Mellitus: A Case-Control Study

Abstract

Ceramides, a sphingolipid group that acts as a messenger in cellular differentiation, proliferation, apoptosis and senescence, have been associated with cardiovascular disease and type 2 diabetes. The evidence for an association between ceramides and gestational diabetes mellitus (GDM) is scarce. This case-control study aimed to compare women with GDM with healthy, pregnant women in terms of plasma ceramide concentrations at the time of delivery. Ninety-two pregnant women were included in this case-control study, 29 in the GDM group and 63 in the control group. All women were admitted to a tertiary academic hospital for a full-term delivery. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) was applied for the quantification of four molecular ceramides, namely Cer d18:1/16:0 (Cer16:0), Cer d18:1/18:0 (Cer18:0), Cer d18:1/24:0 (Cer24:0) and Cer d18:1/24:1 (Cer24:1) in plasma samples. The raw chromatographic data obtained from the LC-MS/MS analysis were processed using Analyst SCIEX (AB Sciex Pte. Ltd., USA). In a univariate statistical analysis, Cer24:0 concentration was significantly lower in the GDM group compared with the control group (p = 0.01). The present study demonstrated lower Cer24:0 concentrations in pregnancies complicated by GDM. Further prospective studies are required to enhance the results of this study.

Ceramides during Pregnancy and Obstetrical Adverse Outcomes

“…Changes in specific ceramide concentrations (increased 18:0, 18:1 and decreased ceramide 24:0) in early pregnancy increase the risk of GDM [77]. Decreased ceramide 24:0 concentrations were reported in the only study in full-term pregnancies complicated by GDM [26]. Although epidemiological studies have suggested that lipid metabolic profiles differ between women with and without GDM [78], most suffer from reverse causation bias and rarely study the first trimester of pregnancy, which is crucial for the development of GDM.…”

“…These responses render them relevant to many diseases. Ceramides potentially contribute to the pathogenesis of various autoimmune conditions, including rheumatic diseases and psoriasis, and cardiovascular and metabolic disorders, such as insulin resistance, diabetes, and gestational diabetes [2,6,[19][20][21][22][23][24][25][26]. Emerging evidence suggests an association with cancer through epigenetic mechanisms and psychiatric disorders [27,28].…”

Human Milk Composition Is Associated with Maternal Body Mass Index in a Cross-Sectional, Untargeted Metabolomics Analysis of Human Milk from Guatemalan Mothers

“…Similarly, we observed a positive association between maternal BMI and a lipid biomarker, Cer(D18:1/16:0), which is one of the most well-studied and validated lipid biomarkers predictive of morbidity and mortality, including GDM [ 59 ]. A nested case-control study from a prospective cohort of pregnant females identified that high Cer18:1 was associated with higher GDM risk [ 60 ]. Another study demonstrated that Cer18:1 concentration was higher among females who eventually developed GDM, compared with females with normal glucose tolerance [ 61 ].…”

Effects of Pregnancy on Plasma Sphingolipids Using a Metabolomic and Quantitative Analysis Approach

“…The impact of sphingosine 1-phosphate and ceramides on endothelial function and vasodilation have been evaluated and found to be critical for a healthy pregnancy [ 20 , 21 ]. Lipids, such as S1P mediate the endothelial effects of high-density lipoprotein (HDL).…”