Dietary Regulation of Lipid Metabolism in Gestational Diabetes Mellitus: Implications for Fetal Macrosomia

Abstract

The primary therapeutic approach for managing hyperglycemia today is diet therapy. Lipids are not only a source of nutrients but also play a role in initiating adipocyte differentiation in the fetus, which may explain the development of fetal macrosomia and future metabolic disorders in children born to mothers with gestational diabetes mellitus (GDM). Alterations in the maternal blood lipid profile, influenced by adherence to a healthy diet in mothers with GDM and the occurrence of fetal macrosomia, represent a complex and not fully understood process. The aim of this study was to examine the characteristics of the blood plasma lipid profile in pregnant women with GDM across all trimesters based on adherence to diet therapy. The clinical part of the study followed a case-control design, including 110 women: 80 in the control group, 20 in a GDM group adhering to the diet, and 10 in a GDM group not adhering to the diet. The laboratory part was conducted as a longitudinal dynamic study, with venous blood samples collected at three time points: 11-13, 24-26, and 30-32 weeks of pregnancy. A significant impact of diet therapy on the composition of blood lipids throughout pregnancy was demonstrated, starting as early as the first trimester. ROC analysis indicated high effectiveness of the models developed, with an AUC of 0.98 for the 30- to 32-week model and sensitivity and specificity values of 1 and 0.9, respectively. An association was found between dietary habits, maternal blood lipid composition at 32 weeks, and newborn weight. The changes in lipid profiles during macrosomia development and under diet therapy were found to be diametrically opposed, confirming at the molecular level that diet therapy can normalize not only carbohydrate metabolism but also lipid metabolism in both the mother and fetus. Based on the data obtained, it is suggested that after further validation, the developed models could be used to improve the prognosis of macrosomia by analyzing blood plasma lipid profiles at various stages of pregnancy.

Keywords: diet therapy; gestational diabetes mellitus; lipidome; macrosomia; mass spectrometry; obesity.

Figure 1

Plots of scores based on the results of OPLS-DA of the lipidomic profile of blood plasma in patients at (A) 11–13, (B) 24–26, and (C) 30–32 weeks of pregnancy who were prescribed dietary therapy. Green dots correspond to patients following the diet, red dots to those not following the diet.

Figure 2

Results of the ROC analysis of OPLS-DA models that differentiate plasma samples from patients adhering to or not adhering to a diet. Samples were taken at 11–13, 24–26, and 30–32 weeks of pregnancy.

Figure 3

Box plot of lipid levels that were most significant for classifying patients who adhered to the diet and those who did not. The data are provided for the model based on the analysis of samples obtained at (A) 11–13 weeks, (B) 24–26 weeks, and (C) 30–32 weeks of pregnancy. * p-value ≤ 0.05; ** p-value ≤ 0.01; *** p-value ≤ 0.001.

Figure 4

The graph is based on the results of OPLS analysis of the lipidomic profile of plasma from patients at 30–32 weeks of pregnancy who were prescribed diet therapy. Green dots correspond to patients adhering to the diet, and red dots to those not adhering to the diet. N represents patients with normal fetal size, and M represents patients with fetal macrosomia.