Dataset Information

Complex Interactions Between Circulating Fatty Acid Levels, Desaturase Activities, and the Risk of Gestational Diabetes Mellitus: A Prospective Cohort Study.

ABSTRACT:

Objective

Maternal abnormal fatty acid desaturation has previously been linked to gestational diabetes mellitus (GDM). However, few studies have investigated this relationship longitudinally throughout pregnancy. In this study, we investigated the relationship between GDM and desaturase activities across the pregnancy trimesters.

Methods

A total of 661 women (GDM = 189, non-GDM = 472) were selected from the Complex Lipids in Mothers and Babies (CLIMB) cohort study. Clinical information and maternal serum were collected at 11-14, 22-28, and 32-34 weeks of gestation. Totally, 20 serum fatty acids were quantified using gas chromatography-mass spectrometry (GC-MS) analysis at each timepoint. Polyunsaturated fatty acid (PUFA) product-to-precursor ratios were used to estimate desaturase and elongase activities including delta-5 desaturase, delta-6 desaturase, stearoyl-CoA desaturase, and elongase.

Results

After adjusting for major potential confounders including maternal age, BMI, primiparity, smoking, and alcohol consumption, we observed a significant increase in the levels of γ-linolenic acid (GLA) and eicosatrienoic acid (DGLA) in the first trimester of women with GDM, whereas GLA and DGLA were reduced in the third trimester, when compared to the non-GDM group. Arachidonic acid (AA) showed an upward trend in the GDM group throughout pregnancy. Estimated delta-6 desaturase and delta-5 desaturase activity were elevated in the first trimester (OR = 1.40, 95% CI 1.03-1.91; OR = 0.56, 95% CI 0.32-0.96) but attenuated in the third trimester (OR = 0.78, 95% CI 0.58-1.07; OR = 2.64, 95% CI 1.46-4.78) in GDM pregnancies, respective to controls. Estimated delta-9-18 desaturase activity (OR = 3.70, 95% CI 1.49-9.19) was increased in women with GDM in later pregnancy.

Conclusions

Our study highlights the potential importance of fatty acid desaturase activities, particularly estimated delta-5 desaturase and delta-9-18 desaturase in the pathophysiology of GDM. These findings may have applications for the early diagnosis and management of GDM.

SUBMITTER: Liu Y

PROVIDER: S-EPMC9313599 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Similar Datasets

Project description:BackgroundPrevious studies have analyzed the associations between the circulating saturated fatty acids (SFAs) and gestational diabetes mellitus (GDM), but no consistent conclusions have been reached. The aim of this study was to evaluate whether plasma SFAs were in correlation with GDM risks in our in-house women cross-sectional study and to better define their associations on the clinical evidence available to date by a dose-response meta-analysis.MethodsWe carried out a cross-sectional study of 807 pregnant women in 2018-2019 (Shanghai, China). GDM was defined according to the criteria of the International Association of Diabetes and Pregnancy Study Groups (IADPSG). Gas chromatography was used to determine the plasma fatty acids (FAs) in the 24-28 gestational weeks. The SFAs levels of non-GDM and GDM participants were compared by Mann-Whitney test, and the association between SFAs and GDM was explored by multivariate logistic models. Further, the potential diagnostic value of plasma SFAs was evaluated using the method of receiver operating characteristic (ROC) analysis. For meta-analysis, five databases were systematically searched from inception to March 2022, and we included 25 relevant studies for calculating pooled standard mean differences (SMDs) and 95% CI to describe the differences in SFAs profiles between non-GDM and GDM women. Study-specific, multivariable-adjusted ORs and 95% CI were also pooled using a fixed-effect model or random-effects model according to the heterogeneity to evaluate the associations between circulating SFAs and GDM prevalence.ResultsIn our cross-sectional study, we found plasma proportion of palmitic acid (C16:0) was positively associated (aOR: 1.10 per 1% increase; 95% CI: 1.04, 1.17), while plasma stearic acid (C18:0) (aOR: 0.76 per 1% increase; 95% CI: 0.66, 0.89), arachidic acid (C20:0) (aOR: 0.92 per 0.1% increase; 95% CI: 0.87, 0.97), behenic acid (C22:0) (aOR: 0.94 per 0.1% increase; 95% CI: 0.92, 0.97), and lignoceric acid (C24:0) (aOR: 0.94 per 0.1% increase; 95% CI: 0.92, 0.97) were inversely associated with GDM. The area under the receiver operative characteristic curve increased from 0.7503 (the basic diagnostic model) to 0.8178 (p = 0.002) after adding total very-long-chain SFAs (VLcSFAs). A meta-analysis from 25 studies showed the circulating levels of three individual SFAs of GDM women were different from those of normal pregnant women. The summarized ORs for GDM was 1.593 (95% CI: 1.125, 2.255, p = 0.009), 0.652 (95% CI: 0.472, 0.901, p = 0.010) and 0.613 (95% CI: 0.449, 0.838, p = 0.002), respectively, comparing the highest vs. lowest quantile of the concentrations of C16:0, C22:0, and C24:0.ConclusionOur results, combined with the findings from meta-analysis, showed that women with GDM had a particular circulating SFA profile, characterized by higher levels of palmitic acid, and lower levels of VLcSFAs. Alterations in the chain lengths of blood SFA profile were shown to be associated with the occurrence of GDM.

Project description:Aims/introductionMilk fat globule-epidermal growth factor 8 (MFG-E8) is the key mediator in anti-inflammatory responses that facilitate phagocytosis of apoptotic cells, and play an essential role in type 2 diabetes and pregnancy, both of which are under a low-grade inflammatory state. However, the action of MFG-E8 in gestational diabetes mellitus (GDM) is unclear. We measured plasma MFG-E8 levels in pregnancy and GDM for the first time, and elucidated possible relationships between its plasma levels and various metabolic parameters.Materials and methodsPlasma MFG-E8 levels were quantified by enzyme-linked immunosorbent assay in 66 women with GDM, 70 with normal pregnancy (p-NGT) and 44 healthy non-pregnant controls (CON), who were matched for age and body mass index. Inflammatory factors tumor necrosis factor-? (TNF-?) and C-reactive protein levels were measured, oral glucose tolerance test was carried out and ?-cell function was evaluated.ResultsPlasma MFG-E8 levels were remarkably higher in p-NGT than in CON (P = 0.024), and were further elevated in GDM vs p-NGT (P = 0.016). MFG-E8 concentrations correlated positively with hemoglobin A1c, glucose levels and insulin resistance (homeostasis model assessment for insulin resistance), and correlated inversely with TNF-? and insulin secretion evaluated by disposition indices in pregnancies. Fasting glucose levels, disposition index of first phase insulin secretion and TNF-? were independent predictors of MFG-E8 levels in pregnancies. Logistic regression analyses showed that women in the third tertile of MFG-E8 levels had a markedly elevated risk of GDM.ConclusionsCirculating MFG-E8 levels are dramatically elevated in pregnancy, and are significantly higher in GDM vs p-NGT. MFG-E8 concentrations are significantly associated with TNF-?, fasting glucose levels, homeostasis model assessment for insulin resistance and disposition indices. However, further studies are required to elucidate the regulation mechanism of MFG-E8 during pregnancy and GDM.