Supplementation with milk enriched with complex lipids during pregnancy: A double-blind randomized controlled trial.

BACKGROUND: Gangliosides are a class of sphingolipids that are present in the cell membranes of vertebrates. Gangliosides influence a broad range of cellular processes through effects on signal transduction, being found abundantly in the brain, and having a role in neurodevelopment. OBJECTIVE: We aimed to assess the effects of maternal daily consumption of ganglioside-enriched milk vs non-enriched milk and a non-supplemented group of pregnant women on maternal ganglioside levels and pregnancy outcomes. DESIGN: Double-blind parallel randomized controlled trial. METHODS: 1,500 women aged 20-40 years were recruited in Chongqing (China) between 11 and 14 weeks of a singleton pregnancy, and randomized into three groups: Control-received standard powdered milk formulation (≥4 mg gangliosides/day); Complex milk lipid-enhanced (CML-E) group-same formulation enriched with complex milk lipids (≥8 mg gangliosides/day) from milk fat globule membrane; Reference-received no milk. Serum ganglioside levels were measured in a randomly selected subsample of 250 women per group. RESULTS: CML-E milk was associated with marginally greater total gangliosides levels in maternal serum compared to Control (13.02 vs 12.69 µg/ml; p = 0.034) but not to Reference group. CML-E milk did not affect cord blood ganglioside levels. Among the 1500 women, CML-E milk consumption was associated with a lower rate of gestational diabetes mellitus than control milk [relative risk 0.80 (95% CI 0.64, 0.99)], but which was not different to the Reference group. CML-E milk supplementation had no other effects on maternal or newborn health. CONCLUSIONS: Maternal supplementation with milk fat globule membrane, as a source of gangliosides, was not associated with any adverse health outcomes, and did not increase serum gangliosides compared with the non-supplemented reference group. TRIAL REGISTRATION: Chinese Clinical Trial Register (ChiCTR-IOR-16007700). CLINICAL TRIAL REGISTRATION: ChiCTR-IOR-16007700; www.chictr.org.cn/showprojen.aspx?proj=12972.

Complex patterns of circulating fatty acid levels in gestational diabetes mellitus subclasses across pregnancy.

BACKGROUND & AIMS: To investigate the relationship between maternal serum fatty acid levels and gestational diabetes mellitus (GDM) subtypes across pregnancy. METHODS: A total of 680 singleton mothers enrolled in the Complex Lipids in Mothers and Babies (CLIMB) study in Chongqing, China were included. Clinical information and serum samples were collected at gestational weeks (GWs) 11-14, 22-28, and 32-34. 75 g Oral Glucose Tolerance Test (OGTT) was conducted at GW 24-28 and GDM subtypes divided into three groups using International Association of Diabetes and Pregnancy Study Group (IADPSG) guidelines criteria: elevated fasting plasma glucose (FPG group; n = 59); 1-h and/or 2-h post-load glucose (1h/2h-PG group; n = 94); combined group (FPG&1h/2h-PG group; n = 42). Non-GDM pregnancies were included (n = 485) as controls. Twenty fatty acids were quantified in serum using gas chromatography-mass spectrometry (GC-MS) analysis. RESULTS: Overall, most serum fatty acid concentrations increased rapidly from the first to second trimester, followed by a plateauing or reduction in the third trimester (p < 0.001). In cross sectional analysis, fatty acid concentrations were significantly higher in the FPG group at GW 11-14 and decreased in the 1h/2h-PG group at GW 32-34, relative to controls. Moreover, higher α-linolenic acid (ALA; the second tertile: adjusted odds ratio [aOR] = 2.53, 95% CI: 1.17 to 5.47; the third tertile: aOR = 2.60, 95% CI: 1.20 to 5.65) and docosahexaenoic acid (DHA; the second tertile: aOR = 2.34, 95% CI: 1.10 to 4.97; the third tertile: aOR = 2.16, 95% CI: 1.00 to 4.63) were significantly associated with a higher risk of GDM in women with elevated fasting plasma glucose at GW 11-14 (first tertile as reference). CONCLUSIONS: Our findings highlight the importance of considering GDM subtypes for the individualised management of GDM in pregnancy. ALA and DHA in early pregnancy are associated with a higher risk of FPG-GDM subtype. This has widespread implications when recommending n-3 PUFAs supplementation for women with GDM.

Metformin administration during pregnancy attenuated the long-term maternal metabolic and cognitive impairments in a mouse model of gestational diabetes.

BACKGROUND: Gestational diabetes mellitus (GDM) is a metabolic disease that can have long-term adverse effects on the cognitive function of mothers. In our study, we explored the changes in metabolic health and cognitive function in mice of middle- and old- age after exposure to GDM, and whether metformin therapy during pregnancy provided long-term benefits. RESULTS: Mice with GDM demonstrated significant cognitive impairment in old age, which was associated with insulin resistance. Gestational metformin therapy was shown to increase insulin sensitivity and improve cognition. The ovarian aging rate was also accelerated in mice exposed to GDM during pregnancy, which may be related to fatty acid metabolism in the ovaries. CONCLUSION: Treatment with metformin during pregnancy was shown to improve fatty acid metabolism in ovarian tissues. METHOD: During pregnancy, mice were fed with a high-fat diet (GDM group) or a low-fat diet (Control group), and a third group received metformin while receiving a high-fat diet (Treatment group). At 12 months old, the mice completed an oral glucose tolerance test, insulin tolerance test, Morris water maze test, female sex hormones were measured, and metabolite profiles of tissue from the ovaries, hypothalamus, and pituitary glands were analysed using gas chromatography-mass spectrometry.

Gestational Diabetes Mellitus Changes the Metabolomes of Human Colostrum, Transition Milk and Mature Milk.

BACKGROUND Gestational diabetes mellitus (GDM) is a pregnancy complication that is diagnosed by the novel onset of abnormal glucose intolerance. Our study aimed to investigate the changes in human breast milk metabolome over the first month of lactation and how GDM affects milk metabolome. MATERIAL AND METHODS Colostrum, transition milk, and mature milk samples from women with normal uncomplicated pregnancies (n=94) and women with GDM-complicated pregnancies (n=90) were subjected to metabolomic profiling by the use of gas chromatography-mass spectrometry (GC-MS). RESULTS For the uncomplicated pregnancies, there were 59 metabolites that significantly differed among colostrum, transition milk, and mature milk samples, while 58 metabolites differed in colostrum, transition milk, and mature milk samples from the GDM pregnancies. There were 28 metabolites that were found to be significantly different between women with normal pregnancies and women with GDM pregnancies among colostrum, transition milk, and mature milk samples. CONCLUSIONS The metabolic profile of human milk is dynamic throughout the first months of lactation. High levels of amino acids in colostrum and high levels of saturated fatty acids and unsaturated fatty acids in mature milk, which may be critical for neonatal development in the first month of life, were features of both normal and GDM pregnancies.

6-gingerol ameliorates age-related hepatic steatosis: Association with regulating lipogenesis, fatty acid oxidation, oxidative stress and mitochondrial dysfunction.

The prevalence of NAFLD increases with age. As the main active ingredient of ginger, 6-gingerol significantly improves lipid metabolism abnormalities in adult rodents. However, few studies have reported its effect on age-related NAFLD. This study was to investigate the effects of 6-gingerol on age-related hepatic steatosis and its potential targets. As expected, 6-gingerol dramatically normalized the hepatic triglyceride content, plasma insulin and HOMA-IR index of ageing rats. Mechanistically, 6-gingerol affected lipid metabolism by increasing ß-oxidation and decreasing lipogenesis through activation of PPARα and CPT1α and inhibition of DGAT-2. Furthermore, 6-gingerol reversed the decreases in citrate, Cs and ATP, lessened the damage caused by ROS, and upregulated mitochondrial marker enzymes NOX, SDH, and SIRT3 in the ageing liver, indicating its ability to strengthen mitochondrial function. Our results showed 6-gingerol exerted a positive effect on insulin sensitivity by regulating Akt. In conclusion, the hepatic anti-steatotic effect of 6-gingerol is associated with inhibition of de novo lipogenesis, upregulation of fatty acid oxidation, reduction in oxidative stress and synergistic enhancement of mitochondrial function.

The CLIMB (Complex Lipids In Mothers and Babies) study: protocol for a multicentre, three-group, parallel randomised controlled trial to investigate the effect of supplementation of complex lipids in pregnancy, on maternal ganglioside status and subsequent cognitive outcomes in the offspring.

INTRODUCTION: Complex lipids are important constituents of the central nervous system. Studies have shown that supplementation with complex milk lipids (CML) in pregnancy may increase the level of fetal gangliosides (GA), with the potential to improve cognitive outcomes. METHODS AND ANALYSIS: We aim to recruit approximately 1500 pregnant women in the first trimester (11-14 weeks) and randomise them into one of the three treatment groups: standard maternal milk formulation, CML-enhanced maternal milk formulation or no maternal milk intervention with standard pregnancy advice (ie, the standard care). Maternal lifestyle and demographic data will be collected throughout the pregnancy, as well as biological samples (eg, blood, hair, urine, buccal smear, cord blood, cord and placenta samples). Data from standard obstetric care recorded in hospital maternity notes (eg, ultrasound reports, results of oral glucose tolerance test and pregnancy outcome data) will also be extracted. Postnatal follow-up will be at 6 weeks and 12 months of age, at which point infant cognitive development will be assessed (Bayley Scales of Infant Development I). ETHICS AND DISSEMINATION: This project was approved by the Ethics Committee of Chongqing Medical University. Dissemination of findings will take the form of publications in peer-reviewed journals and presentations at national and international conferences. TRIAL REGISTRATION NUMBER: ChiCTR-IOR-16007700; Pre-results.