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Influence of gestational diabetes mellitus on lipid signatures in breast milk and association with fetal physical development.

ABSTRACT: Gestational diabetes mellitus (GDM) commonly leads to adverse pregnancy outcomes and long-term metabolic complications in offspring. Breastfeeding has been shown to rewrite the fetal "metabolic programming" resulting from maternal diabetes and finally lead to a lower risk of future metabolic disease. Lipids in breast milk act like hormones to promote infant growth and development, but there is minimal information invested thus far in constitution changes of lipids in breast milk, especially in the context of GDM. In the present study, we performed a lipidomics analysis to compare the lipid composition in breast milk collected from women with or without GDM. We further revealed the correlations of dysregulated lipids in breast milk with maternal glucose and infant physical development. A total of 833 lipid species from 15 classes were identified, 60 of which were found to be significantly altered in response to the high glucose, suggesting a remarkable lipid profiling change in breast milk induced by GDM. Our results showed significant associations between dysregulated lipids (e.g., neutral lipids, phospholipids, sphingolipids) and maternal glucose. Furthermore, correction analysis demonstrated that GDM related lipids were also associated with indicators of infant physical development, including body weight, length, and head circumference. These findings may help to understand the protective effects of breastfeeding especially during GDM pregnancy.

SUBMITTER: Zhong H

PROVIDER: S-EPMC9402091 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature

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Influence of gestational diabetes mellitus on lipid signatures in breast milk and association with fetal physical development.

Zhong Hong H Zhang Jiahua J Xia Jiaai J Zhu Yuting Y Chen Chen C Shan Chunjian C Cui Xianwei X

Frontiers in nutrition 20220810

Gestational diabetes mellitus (GDM) commonly leads to adverse pregnancy outcomes and long-term metabolic complications in offspring. Breastfeeding has been shown to rewrite the fetal "metabolic programming" resulting from maternal diabetes and finally lead to a lower risk of future metabolic disease. Lipids in breast milk act like hormones to promote infant growth and development, but there is minimal information invested thus far in constitution changes of lipids in breast milk, especially in t ...[more]

PMID: 36034909

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Project description: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.

Project description:BackgroundThird trimester fetal anthropometric parameters are known to predict neonatal complications. A better understanding of predictors of adverse fetal parameters might help to personalize the use and frequency of fetal ultrasound. The objectives of this study were: (a) to evaluate the utility of maternal sociodemographic, anthropometric and metabolic predictors to predict 3rd trimester fetal anthropometric parameters in women with gestational diabetes mellitus (GDM), (b) to assess whether the impact of these maternal predictors is fetal sex-dependent, and (c) to provide a risk stratification for markers of fetal overgrowth (fetal weight centile (FWC) and fetal abdominal circumference centile (FACC) depending on prepregnancy BMI and gestational weight gain (GWG) until the 1st GDM visit.MethodsThis prospective study included 189 women with GDM. Maternal predictors were age, ethnicity, prepregnancy BMI, GWG and excessive weight gain until the 1st GDM visit, fasting, 1-hour and 2-hour blood glucose oral glucose tolerance test values, HbA1c at the 1st visit and medical treatment requirement. Fetal outcomes included FWC, FWC >90% and <10%, FACC, FACC >90% and <10%, at 29 0/7 to 35 6/7 weeks of gestational age. We performed univariate and multivariate regression analyses and probability analyses.ResultsIn multivariate analyses, prepregnancy BMI was associated with FWC, FWC > 90% and FACC. GWG until the 1st GDM visit was associated with FWC, FACC and FACC > 90% (all p ≤ 0.045). Other maternal parameters were not significantly associated with fetal anthropometry in multivariate analyses (all p ≥ 0.054). In female fetuses, only GWG was associated with FACC (p= 0.044). However, in male fetuses, prepregnancy BMI was associated with FWC, FWC > 90% and FACC and GWG with FWC in multivariate analyses (all p ≤ 0.030). In women with a prepregnancy BMI of ≥ 25 kg/m2 and a GWG until the 1st GDM visit ≥ 10.3 kg (mean GWG), the risk for FWC > 90% and FACC > 90% was 5.3 and 4 times higher than in their counterparts.ConclusionsA personalized fetal ultrasound surveillance guided by fetal sex, prepregnancy BMI and GWG may be beneficial in reducing adverse fetal and neonatal outcomes.

Project description:BackgroundGestational diabetes mellitus (GDM) has been associated with several fetal complications, such as macrosomia and fetal growth restriction (FGR). Infants from GDM associated FGR are at increased risk for adult-onset obesity and associated metabolic disorders. However, the underlying mechanisms of GDM associated FGR remain to be explored.MethodsWe analyzed placentas from GDM patients with FGR for ferroptosis markers and GLUT1 expression. High glucose conditions were established by adding different concentrations of D-Glucose to the 1640 cell culture medium. RSL3 were used to test ferroptosis sensitivity in trophoblast cells. GLUT1 was inhibited using siRNA or its inhibitor WZB117 to assess its impact on ferroptosis inhibition in HTR8/SVneo cell line. Mechanistic studies explored the effects of GLUT1 on AMPK and ACC phosphorylation, which in turn impacted lipid metabolism and ferroptosis. In mouse models, streptozotocin (STZ)-induced GDM was treated with WZB117 and the ferroptosis inhibitor liproxstatin-1 (Lip-1). Finally, AMPK and ACC phosphorylation levels were evaluated in GDM patient samples.ResultsIn this study, placentas from GDM patients with FGR showed signs of ferroptosis and upregulation of GLUT1. In cell models, high glucose conditions sensitized trophoblast cells to ferroptosis and induced GLUT1 expression. Interestingly, GLUT1 inhibition significantly suppressed ferroptosis in trophoblast cells under high glucose conditions. Mechanistically, elevated GLUT1 inhibited AMPK phosphorylation and reduced ACC phosphorylation, thereby promoting lipid synthesis and facilitating ferroptosis. In pregnant mice, STZ-induced hyperglycemia led to FGR, and treatment with either the GLUT1 inhibitor WZB117 or the ferroptosis inhibitor Lip-1 alleviated the FGR phenotype. Moreover, in vivo elevation of GLUT1 increased ferroptosis markers, decreased AMPK/ACC phosphorylation, and resulted in altered lipid metabolism, which likely contributed to the observed phenotype. Finally, placental samples from GDM patients showed reduced AMPK and ACC phosphorylation.ConclusionsOur findings suggest a potential role of ferroptosis in GDM associated FGR and indicate that the dysregulated GLUT1-AMPK-ACC axis may be involved in the pathogenesis of GDM associated FGR in clinicals.

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Influence of gestational diabetes mellitus on lipid signatures in breast milk and association with fetal physical development.

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Influence of gestational diabetes mellitus on lipid signatures in breast milk and association with fetal physical development.

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