Maternal Gestational Diabetes Mellitus Research Articles

Vitamin B12 in Pregnancy and its Relationship with Maternal BMI and Gestational Diabetes Mellitus

Objectives:To determine the levels of vitamin B12 in pregnant women and to explore the relationship of vitamin B12 with maternal BMI and gestational diabetes mellitus.Methods:This cross-sectional study was conducted at Department of Physiology, UHS, Lahore from February 2019 to March 2020. Ninety pregnant women in early third trimester of pregnancy were selected. Forty-five women had gestational diabetes and forty-five were healthy pregnant women. Serum vitamin B12 and fasting blood glucose (FBG) levels were determined by ELISA and glucose oxidase method respectively. 1st trimester BMI was also recorded. SPSS version 23 was used to analyze the data.Results:Serum vitamin B12 was significantly lower in GDM group (149.41±13.66) as compared to non-GDM group (357.49±42.07). BMI was significantly higher in GDM group (32.94±2.10) as compared to non-GDM group (23.52±1.83). Significant negative correlation (-0.78**) was observed between 1st trimester BMI and vitamin B12 in late pregnancy. Regression analysis revealed that high BMI was associated with decrease in vitamin B12 and increased risk of gestational diabetes mellitus (3.26***). Moreover, vitamin B12 was partially mediating the relationship between BMI and FBG.Conclusion:Low vitamin B12 levels have an association with maternal BMI and gestational diabetes mellitus.

Breastfeeding and Gestational Diabetes: Overview in México

Gestational diabetes mellitus is defined as glucose intolerance first detected during pregnancy. Maternal obesity and gestational diabetes mellitus have been associated with more difficulties in the establishment and duration of breastfeeding among mothers with gestational diabetes mellitus who have a body mass index above their healthy, normal weight counterparts; plus the large number of social and economic factors that prevent the establishment of satisfactory breastfeeding, makes it essential to provide systematic support, especially in the first days of life, remembering that breastfeeding in turn reduces the risk of diabetes in women. Mexico is a middle-high income Latin American country; studies conducted in metropolitan areas with larger populations indicate that exclusive breastfeeding is often initiated, but it is difficult to continue it; together with the increase in the prevalence of obesity and diabetes mellitus in the population, it is of great importance to integrate maternal and child nutrition policies focused on the prevention of obesity and chronic diseases, as well as practices that contribute to the promotion and support to mothers to achieve successful breastfeeding, at least during the first 6 months of life.

Smokeless Tobacco Exposure and Fetal Iron Status: An Analytical Study.

Objectives:To compare the cord serum ferritin and fetal iron status in newborns with and without maternal occupational smokeless tobacco exposure and determine the influencing factors.Methods:This cross-sectional study included mother–infant dyads with occupational tobacco exposure (exposed) and an unexposed group. Umbilical cord serum ferritin was compared in both groups. Fetal nicotine absorption was established by cord cotinine.Results:A total of 140 newborns each were analyzed in each group. There was no significant mean difference (MD) (P = 0.900) between the cord serum ferritin in the tobacco exposed and unexposed group. Fetal nicotine absorption was seen in 43.6% of the exposed group. Cord serum ferritin was 14.1 μg/L (95% confidence interval [(95% CI:-43.1, 14.9); P=0.338] lower in this group compared with the group without fetal nicotine absorption. A higher adjusted MD for ferritin was present for maternal hypertension (12.5 [95% CI: −75.5, 100.5]; P = 0.777) and gestational diabetes mellitus (21.4 [95% CI: −54.0, 96.9]; P = 0.571) in the group with fetal nicotine absorption. Fetal nicotine absorption exaggerated fetal iron depletion in maternal anemia [aOR 4.8 (95%CI: 1.2, 19.0); P=0.025].Conclusion:Cord serum ferritin and fetal iron status were comparable in tobacco exposed and unexposed groups. In those with fetal nicotine absorption, cord ferritin levels reflect the fetal inflammatory state.

Placental lipid transport and content in response to maternal overweight and gestational diabetes mellitus in human term placenta

Background and aimsPlacental lipid transport is altered in women with high prepregnancy body mass index (pre-BMI) or gestational diabetes (GDM), which consequently affects foetal growth. However, the interaction of maternal overweight (OW) and GDM on placental lipid metabolism and possible adaptations are less studied. We aimed to examine whether maternal OW or GDM is the main factor disrupting placental lipid processing in human term placenta. Methods and resultsA total of 152 lean (18.5 ≤ pre-BMI ≤ 23.9 kg/m2) and OW (24 ≤ pre-BMI ≤ 27.9 kg/m2) pregnant women with or without GDM with a scheduled delivery by caesarean section were recruited. Maternal venous blood samples were used to measure metabolic parameters during pregnancy. Term placentas and cord blood were collected at delivery to determine placental lipid metabolism and foetal circulating lipid levels. Maternal OW significantly increased the placental mRNA expression of genes involved in lipid metabolism (FAT/CD36, FATP1, FATP4, FATP6, and PPAR-α), elevated placental lipid content (triglyceride, cholesterol), enhanced placental mTORC1-rpS6 and ERK1/2 signalling, increased cord blood insulin levels and birth weight. Neonatal birth weight was positively correlated with maternal pre-BMI, placental ERK1/2 signalling and cord blood insulin. There was an interaction between OW and GDM in regulating key placental fuel transport and storage gene expression (LPL, FATP6, FABP7, PPAR-α, PPAR-β, PPAR-γ, IR-β, GLUT1, SNAT2, SNAT4, and LAT1). ConclusionMaternal OW mainly affects placental lipid metabolism, which may contribute to foetal overgrowth and may impact long-term offspring health. GDM plays a less significant role in affecting placental lipid transfer and other mechanisms may be involved.

Associations between endocrine-disrupting heavy metals in maternal hair and gestational diabetes mellitus: A nested case-control study in China.

Exposure to environmental endocrine disruptors (EDCs) may lead to abnormal glucose metabolism and, potentially, gestational diabetes mellitus (GDM). We investigated the association between five endocrine-disrupting heavy metals (EDHMs), i.e., arsenic (As), cadmium (Cd), lead (Pb), mercury (Hg), and tin (Sn), in maternal hair and the risk of GDM. We conducted a nested case-control study including 335 GDM cases and 343 controls without GDM based on a prospective birth cohort established in Beijing, China. Concentrations of EDHMs were analyzed in maternal hair. Log-binomial regression and multiple linear regression were used to estimate the associations between the hair concentrations of single metals and the risk of GDM, while weighted quantile sum (WQS) regression for their mixed effects. The median concentrations of Hg (0.442 vs. 0.403μg/g) and Sn (0.171 vs. 0.140μg/g) in the case group were significantly higher than those in the control group. No differences were found between the two groups for the other three metals. After adjusting for confounders, the prevalence ratio (PR; highest vs. lowest tertile) of GDM risk for Hg was 1.27 (95% confidence interval [CI]: 1.05-1.54), while that for Sn was 1.26 (95% CI: 1.04-1.53). Among women with a body mass index<24kg/m2, the PR (highest vs. lowest tertile) of GDM for Sn was 1.38 (95% CI: 1.09-1.75). The effect of exposure to the five EDHMs on the risk of GDM was estimated by WQS regression: Sn and Hg made the largest contributions to the WQS index (40.9% and 40.3%, respectively). High maternal levels of EDHMs, particularly Sn and Hg, may promote the development of GDM.

Differential analysis of the bacterial community in colostrum samples from women with gestational diabetes mellitus and obesity

Gestational Diabetes Mellitus (GDM) and obesity affect the functioning of multiple maternal systems and influence colonization of the newborn gastrointestinal through the breastmilk microbiota (BMM). It is currently unclear how GDM and obesity affect the human BMM composition. Here, we applied 16S-rRNA high-throughput sequencing to human colostrum milk to characterize BMM taxonomic changes in a cohort of 43 individuals classified in six subgroups according to mothers patho-physiological conditions (healthy control (n = 18), GDM (n = 13), or obesity (n = 12)) and newborn gender. Using various diversity indicators, including Shannon/Faith phylogenetic index and UniFrac/robust Aitchison distances, we evidenced that BMM composition was influenced by the infant gender in the obesity subgroup. In addition, the GDM group presented higher microbial diversity compared to the control group. Staphylococcus, Corynebacterium 1, Anaerococcus and Prevotella were overrepresented in colostrum from women with either obesity or GDM, compared to control samples. Finally, Rhodobacteraceae was distinct for GDM and 5 families (Bdellovibrionaceae, Halomonadaceae, Shewanellaceae, Saccharimonadales and Vibrionaceae) were distinct for obesity subgroups with an absolute effect size greater than 1 and a q-value ≤ 0.05. This study represents the first effort to describe the impact of maternal GDM and obesity on BMM.

Risks of overweight in the offspring of women with gestational diabetes at different developmental stages: A meta-analysis with more than half a million offspring.

We conducted a meta-analysis to evaluate the association of maternal gestational diabetes mellitus (GDM) and offspring overweight from birth to adulthood, and to assess the effects of lifestyle interventions in women with GDM on this risk of offspring overweight. We identified literature from PubMed and 12 other electronic databases and retrieved relevant literature published before October 20, 2020. Random-effects model analysis was used to calculate relative risks (RRs) of overweight and weighted mean differences of body mass index among children stratified into different developmental stages. Forty-nine cohort studies (n = 559,377) and four randomized controlled trials (n = 1277) were included. We found that offspring of women with GDM were at an increased risk for overweight with age, from 1.14 (95% confidence interval [CI]: 1.06-1.22) under 5 years, 1.37 (95% CI: 1.31-1.44) at 5 to <10 years, 2.00 (95% CI: 1.79-2.23) at 10 to <18 years, to 2.05 (95% CI: 1.65-2.55) over 18 years of age (p < 0.05 for differences among groups). However, it was not observed that lifestyle interventions for GDM decreased the elevated overweight risk (RR: 0.94, 95% CI: 0.80-1.11, I2 = 0.0%). These findings highlight the need for adopting an active and healthy lifestyle in this high-risk group.

The mediating role of gestational diabetes mellitus in the associations of maternal prepregnancy body mass index with neonatal birth weight.

BackgroundBoth prepregnancy obesity and gestational diabetes mellitus (GDM) have been linked to adverse neonatal birth weight. However, the mediating role of GDM between prepregnancy obesity and neonatal birth weight is unclear.MethodThe cohort study included 17 260 singleton pregnant women and their newborns. Participants' demographic characteristics, disease history, family history of the disease, and the perinatal outcomes were recorded. The association between maternal prepregnancy body mass index (BMI) status and small for gestational age (SGA) or large for gestational age (LGA) neonates was analyzed using logistic regressions, before and after adjusting for covariates and GDM. The potential mediation of GDM on the association between prepregnancy BMI and adverse birth weight was examined.ResultMultivariate logistic regression demonstrated that prepregnancy underweight women were more likely to deliver SGA neonates compared to those who had normal weights, whereas prepregnancy obese pregnant women were more likely to have LGA neonates. The RMediation analyses illustrated that the mediation effect of GDM on the maternal prepregnancy BMI (continuous variable) and the risk of SGA was not significant, whereas the association between prepregnancy BMI and LGA was statistically mediated by GDM (95%CI of a*b: 0.009‐0.051). The Iacobacci (2012) method indicated that the impact of maternal prepregnancy overweight (Zmediation = 2.418, P = .015) and obesity (Zmediation = 2.165, P = .030) on LGA was partially mediated by GDM, with an indirect effect of 16.3% and 13.1%, respectively.ConclusionPrepregnancy BMI was observed to be associated with SGA and LGA. The association of prepregnancy overweight and obesity with LGA was found to be partially mediated by GDM.

The epidemiology, clinical, biochemical, immunological and radiological features of youth onset type 2 diabetes mellitus in the state of Qatar.

To describe the epidemiology, clinical, biochemical, immunological and radiological aspects of youth with type 2 diabetes. Patients under 18year of age with type 2 diabetes were recruited from 2018 to 2020, clinical data collected, autoantibodies (GAD65, IAA, IA2 and ZnT8), insulin, ALT and c-peptide were measured. Hepatic ultrasound was performed for assessment of non-alcoholic fatty liver disease (NAFLD). 104 patients were identified. The incidence in 2020 and prevalence per 100,000 was 2.51 and 23.7, respectively. The age of onset was between 8.5 and 18years with 74% of the patients being of Qatari nationality. Males were more affected than females (1.5/1). Overweight/obesity was present in 98% of all the patients, a positive family history (either both parents or a single parent) in 71% and maternal gestational diabetes mellitus (GDM) in 60% of patients. More than 90% of the patients had acanthosis nigricans. 5 patients had 1 autoantibody positivity and hepatic ultrasound detected evidence of NAFLD in majority of patients. Obesity, maternal GDM and family history of diabetes were the key risk factors for the development of type 2 diabetes. Autoantibody positivity may be present in youth type 2 diabetes. As youth type 2 diabetes is associated with early onset microvascular and macrovascular complications, these findings have important social and health budget implications for Qatar. Tackling the burden of maternal GDM and childhood obesity and building programmes for early detection and intervention, are therefore, essential to reduce the risk of future complications.

Maternal but not fetoplacental health can be improved by metformin in a murine diet-induced model of maternal obesity and glucose intolerance.

Maternal obesity is a global problem that increases the risk of short- and long-term adverse outcomes for mother and child, many of which are linked to gestational diabetes mellitus. Effective treatments are essential to prevent the transmission of poor metabolic health from mother to child. Metformin is an effective glucose lowering drug commonly used to treat gestational diabetes mellitus; however, its wider effects on maternal and fetal health are poorly explored. In this study we used a mouse (C57Bl6/J) model of diet-induced (high sugar/high fat) maternal obesity to explore the impact of metformin on maternal and feto-placental health. Metformin (300 mg/kg/day) was given to obese females via the diet and was shown to achieve clinically relevant concentrations in maternal serum (1669±568 nM in late pregnancy). Obese dams developed glucose intolerance during pregnancy and had reduced uterine artery compliance. Metformin treatment of obese dams improved maternal glucose tolerance, reduced maternal fat mass, and restored uterine artery function. Placental efficiency was reduced in obese dams, with increased calcification and reduced labyrinthine area. Consequently, fetuses from obese dams weighed less (p<0.001) at the end of gestation. Despite normalisation of maternal parameters, metformin did not correct placental structure or fetal growth restriction. Metformin levels were substantial in the placenta and fetal circulation (109.7±125.4 nmol/g in the placenta and 2063±2327 nM in fetal plasma). These findings reveal the distinct effects of metformin administration during pregnancy on mother and fetus and highlight the complex balance of risk versus benefits that are weighed in obstetric medical treatments.

A prospective population-based multicentre study on the impact of maternal body mass index on adverse pregnancy outcomes: Focus on normal weight.

Maternal body mass index (BMI) below or above the reference interval (18.5-24.9 kg/m2) is associated with adverse pregnancy outcomes. Whether BMI exerts an effect within the reference interval is unclear. Therefore, we assessed the association between adverse pregnancy outcomes and BMI, in particular within the reference interval, in a general unselected pregnant population. Data was extracted from a prospective population-based multicentre cohort (Risk Estimation for PrEgnancy Complications to provide Tailored care (RESPECT) study) conducted between December 2012 to January 2014. BMI was studied in categories (I: <18.5, II: 18.5-19.9, III: 20.0-22.9, IV: 23.0-24.9, V: 25.0-27.4, VI: 27.5-29.9, VII: >30.0 kg/m2) and as a continuous variable within the reference interval. Adverse pregnancy outcomes were defined as composite endpoints for maternal, neonatal or any pregnancy complication, and for adverse pregnancy outcomes individually. Linear trends were assessed using linear-by-linear association analysis and (adjusted) relative risks by regression analysis. The median BMI of the 3671 included women was 23.2 kg/m2 (IQR 21.1-26.2). Adverse pregnancy outcomes were reported in 1256 (34.2%). Linear associations were observed between BMI categories and all three composite endpoints, and individually for pregnancy-induced hypertension (PIH), preeclampsia, gestational diabetes mellitus (GDM), large-for-gestational-age (LGA) neonates; but not for small-for-gestational-age neonates and preterm birth. Within the reference interval, BMI was associated with the composite maternal endpoint, PIH, GDM and LGA, with adjusted relative risks of 1.15 (95%CI 1.06-1.26), 1.12 (95%CI 1.00-1.26), 1.31 (95%CI 1.11-1.55) and 1.09 (95%CI 1.01-1.17). Graded increase in maternal BMI appears to be an indicator of risk for adverse pregnancy outcomes even among women with a BMI within the reference interval. The extent to which BMI directly contributes to the increased risk in this group should be evaluated in order to determine strategies most valuable for promoting safety and long-term health for mothers and their offspring.

Prenatal exercise in fetal development: a placental perspective.

Maternal obesity (MO) and gestational diabetes mellitus (GDM) are common in Western societies, which impair fetal development and predispose offspring to metabolic dysfunction. Placenta is the organ linking the mother to her fetus, and MO suppresses the development of vascular system and expression of nutrient transporters in placenta, thereby affecting fetal development. For maintaining its proper physiological function, placenta is energy demanding, which is met through extensive oxidative phosphorylation. However, the oxidative capacity of placenta is suppressed due to MO and GDM. Recently, several studies showed that physical activity during pregnancy enhances oxidative metabolism and improves placental function, which might be partially mediated by exerkines, referring to cytokines elicited by exercise. In addition, as an endocrine organ, placenta secretes cytokines, termed placentokines, including apelin, superoxide dismutase 3, irisin, and adiponectin, which mediate fetal development and maternal metabolism. Possible molecular mechanisms linking maternal exercise and placentokines to placental and fetal development are further discussed. As an emerging field, up to now, available studies are limited, mostly conducted in rodents. Given the epidemics of obesity and metabolic disorders, as well as the prevalence of maternal sedentary lifestyle, the effects of exercise of pregnant women on placental function and placentokine secretion, as well as their impacts on fetal development, need to be further examined.

Boys but Not Girls Exposed to Maternal Gestational Diabetes Mellitus Have Unfavorable Fat Distribution

Background: Maternal gestational diabetes mellitus (GDM) and overweight are associated with an increased risk of obesity and the metabolic syndrome in the adult offspring. We studied the influence of maternal GDM on prepubertal children’s body composition and bone mineral biochemistry. Methods: A total of 134 prepubertal Caucasian children (age range 4.4–9.7 years) were studied in a controlled cross-sectional study. Seventy-six children had been exposed to maternal GDM and 58 children born after a normal pregnancy served as controls. The outcome variables were body fat %, android fat %, gynoid fat %, android/gynoid fat ratio, bone mineral density (BMD), bone mineral content (BMC), muscle mass, lean mass (LM) and serum 25-hydroxyvitamin D, ionized calcium, phosphate, and alkaline phosphatase concentrations. Results: There were no differences in body fat %, android fat %, BMD, BMC, muscle mass, or LM between the study groups. Gynoid fat % was higher in the GDM than control children (p = 0.03). Android fat %, gynoid fat %, and android/gynoid fat ratio were higher in the GDM boys than control boys (p = 0.046, 0.037, and 0.038) respectively, but no differences were found between the GDM and control girls. Conclusions: Boys exposed to maternal GDM presented with more unfavorable fat distribution than their controls, whereas no difference was found between the girls. Otherwise, the differences in body composition were minimal between prepubertal GDM and control children.

Novel epigenetic link between gestational diabetes mellitus and macrosomia.

Background & objectives: Examine maternal gestational diabetes mellitus (GDM), macrosomiaand DNA methylation in candidate genes IGF1, IGF2, H19, ARHGRF11, MEST, NR3C1, ADIPOQand RETN. Materials & methods: A total of 1145children(572 GDM cases and 573 controls) from the Tianjin GDM study, including 177 with macrosomia, had blood DNA collection at median age 5.9 (range: 3.1-10.0). We used logistic regression to screen for associations with GDM and model macrosomia on 37 CpGs, and performed mediation analysis. Results: One CpG was associated with macrosomia at false discovery rate (FDR) <0.05 (cg14428359 in MEST); two (cg19466922 in MEST and cg26263166 in IGF2) were associated at p<0.05 but mediated 26and 13%, respectively. Conclusion:MEST and IGF2 were previously identified for potential involvement in fetal growth and development (Trial Registration number: NCT01554358 [ClinicalTrials.gov]).

Differential Effects of Gestational Diabetes Mellitus on Preterm Birth between Nullipara and Multipara: A Population-Based Cohort Study

Background: The differential effect of gestational diabetes mellitus (GDM) on preterm birth according to parity has not been fully addressed. Herein we conducted a city-wide population-based cohort study aiming to determine the association between maternal GDM and offspring prematurity stratified by parity. Methods: We conducted a cohort study of all pregnant women in Qingdao during August 1, 2018, to June 30, 2020. Multivariate logistic regression analysis and propensity score (PS) matching analyses were performed to balance confounding bias in estimation of the GDM effect on premature birth. Odds ratio (OR) of matched samples was calculated from conditional logistic regression. Association between maternal GDM and premature birth was examined using stratified analyses based on parity status. Findings: A total of 105768 mother-child pairs were included in our analysis. Overall, more than 98.72% of the women with GDM during pregnancy were successfully matched, resulting in 16613 equal-sized cohort pairs. In the PS adjusted analysis, multiparous mothers with current and previous GDM were at a significantly higher risk of giving a premature birth than those without GDM (OR= 1.78, 95% confidence interval [CI]: 1.19-2.71). However, such association did not hold true for PS matched samples of nullipara (OR= 1.14, 95%CI: 0.90-1.44). The risk estimates for maternal GDM on moderate preterm birth were similar to that of preterm birth. There was an inverse association between GDM and very preterm birth among nullipara in PS matched models (OR= 0.29, 95% CI: 0.08-0.83). While no association between GDM and very preterm birth was observed in multipara (all P >0.05). Interpretation: The effect of maternal GDM on offspring prematurity differed with parity status. For nulliparous mothers, there was no association between GDM and premature birth , while among multiparous mothers with current and previous GDM, an increased risk for prematurity was observed. There was even a protective effect of GDM against very preterm birth among nulliparous mothers. Pregnancy care should consider parity and GDM for better prediction and intervention of preterm. Funding: The National Natural Science Foundation of China (NSFC), [Grant No.81903335] &China Postdoctoral Science Foundation Funded Project [Grant No.2019M662307]. Declaration of Interest: We declare no competing interests. Ethical Approval: The study was approved by the Institutional Review Board of Qingdao Women and Children’s Hospital Ethics (No. 002-2018-FEKY).

Epigenetic Changes in Neonates Born to Mothers With Gestational Diabetes Mellitus May Be Associated With Neonatal Hypoglycaemia.

The detection of epigenetic changes associated with neonatal hypoglycaemia may reveal the pathophysiology and predict the onset of future diseases in offspring. We hypothesized that neonatal hypoglycaemia reflects the in utero environment associated with maternal gestational diabetes mellitus. The aim of this study was to identify epigenetic changes associated with neonatal hypoglycaemia. The association between DNA methylation using Infinium HumanMethylation EPIC BeadChip and neonatal plasma glucose (PG) level at 1 h after birth in 128 offspring born at term to mothers with well-controlled gestational diabetes mellitus was investigated by robust linear regression analysis. Cord blood DNA methylation at 12 CpG sites was significantly associated with PG at 1 h after birth after adding infant sex, delivery method, gestational day, and blood cell compositions as covariates to the regression model. DNA methylation at two CpG sites near an alternative transcription start site of ZNF696 was significantly associated with the PG level at 1 h following birth (false discovery rate-adjusted P < 0.05). Methylation levels at these sites increased as neonatal PG levels at 1 h after birth decreased. In conclusion, gestational diabetes mellitus is associated with DNA methylation changes at the alternative transcription start site of ZNF696 in cord blood cells. This is the first report of DNA methylation changes associated with neonatal PG at 1 h after birth.

Detecting cord blood cell type-specific epigenetic associations with gestational diabetes mellitus and early childhood growth

BackgroundEpigenome-wide association studies (EWAS) have provided opportunities to understand the role of epigenetic mechanisms in development and pathophysiology of many chronic diseases. However, an important limitation of conventional EWAS is that profiles of epigenetic variability are often obtained in samples of mixed cell types. Here, we aim to assess whether changes in cord blood DNA methylation (DNAm) associated with gestational diabetes mellitus (GDM) exposure and early childhood growth markers occur in a cell type-specific manner.ResultsWe analyzed 275 cord blood samples collected at delivery from a prospective pre-birth cohort with genome-wide DNAm profiled by the Illumina MethylationEPIC array. We estimated proportions of seven common cell types in each sample using a cord blood-specific DNAm reference panel. Leveraging a recently developed approach named CellDMC, we performed cell type-specific EWAS to identify CpG loci significantly associated with GDM, or 3-year-old body mass index (BMI) z-score. A total of 1410 CpG loci displayed significant cell type-specific differences in methylation level between 23 GDM cases and 252 controls with a false discovery rate < 0.05. Gene Ontology enrichment analysis indicated that LDL transportation emerged from CpG specifically identified from B-cells DNAm analyses and the mitogen-activated protein kinase pathway emerged from CpG specifically identified from natural killer cells DNAm analyses. In addition, we identified four and six loci associated with 3-year-old BMI z-score that were specific to CD8+ T-cells and monocytes, respectively. By performing genome-wide permutation tests, we validated that most of our detected signals had low false positive rates.ConclusionCompared to conventional EWAS adjusting for the effects of cell type heterogeneity, the proposed approach based on cell type-specific EWAS could provide additional biologically meaningful associations between CpG methylation, prenatal maternal GDM or 3-year-old BMI. With careful validation, these findings may provide new insights into the pathogenesis, programming, and consequences of related childhood metabolic dysregulation. Therefore, we propose that cell type-specific analyses are worth cautious explorations.

Rodents on a High-Fat Diet Born to Mothers with Gestational Diabetes Exhibited Sex- Specific Lipidomic Changes in Reproductive Organs, Hormonal Imbalances and Insulin Resistance

Background: Maternal gestational diabetes mellitus (GDM) and offspring high-fat diet (HFD) have shown to have sex-specific detrimental effects on the health of offspring. Methods: A maternal GDM mice model was established by feeding maternal C57BL/6 mice HFD and then their offspring were exposed to either HFD or low-fat diet. Testes, ovaries, liver and gonadal adipose tissue were collected from offspring at 20 weeks, and their reproductive lipidomic profiles were characterized using gas chromatography-mass spectrometry. Findings: Male offspring following HFD had a substantially elevated body weight. In reproductive organs and hormones, male offspring from GDM mothers had decreased testes weights and testosterone levels, while female offspring from GDM mothers had increased ovary weights and estrogen levels. AKT pathway were increased in the offspring liver and gonadal adipose tissue of those fed with HFD. The fatty acid profiling showed that testes were prone to the effect of maternal GDM, whereas ovarian metabolite profiles were upregulated in maternal GDM and downregulated in offspring following HFD. Eicosapentaenoic acid were attenuated in both maternal serum and offspring testes under the impact of maternal GDM and in offspring following HFD. Interpretation: Maternal GDM and offspring HFD have different metabolic effects on offspring reproductive organs, and PUFAs may protect against detrimental outcomes in offspring such as obesity. Funding: the National Natural Science Foundation of China, The 111 Project, The National Key Research and Development Program of Reproductive Health & Major Birth Defects Control and Prevention, Chongqing Health Commission, Kuanren Talents Programs, and Chongqing Science & Technology Commission. Declaration of Interest: Andi Wang, Xinyang Yu, Zhu Chen, Yinyin Xia, Chang Chen, Hongbo Qi, Philip N. Baker, Richard Saffery, Ting-Li Han and Hua Zhang declare that they have no conflict of interest. Ethical Approval: All WT C57BL/6 mice in this study were purchased from the Model Animal Research Center of Nanjing University. All animal experiments complied with the ARRIVE guidelines and approved by the Ethics Committee of the First Affiliated Hospital of Chongqing Medical University (Batch number: 2020-41).

Maternal gestational diabetes and childhood hyperlipidemia.

Aim of this study is to assess dyslipidemia risk between children exposed to maternal gestational diabetes mellitus (GDM) and those not exposed. We recruited 1144mother-child pairs (572 GDM and 572 non-GDM women matched by their offspring's age and sex). The age of offspring ranged from 3 to 9years old. We used general linear models to compare mean values of different lipid profiles among children born to mothers with and without GDM. Logistic regression models were used to assess associations of maternal GDM with abnormal lipid profiles in offspring. After adjustment for maternal and children's characteristics, children born to mothers with GDM had lower mean values of high-density-lipoprotein (HDL) cholesterol (1.40±0.01 vs. 1.50±0.01; p<0.001) and higher mean levels of triglycerides/HDL cholesterol ratio (0.37±0.01 vs. 0.35±0.01; p<0.05) in comparison with their counterparts born to mothers without GDM. Multivariate-adjusted odds ratios among children exposed to mothers with GDM compared with the counterparts were 2.11 (95% confidence interval [CI 1.15-3.88]) for low HDL cholesterol and 1.35 (95% CI 1.00-1.81) for high triglycerides/HDL cholesterol ratio, respectively. Maternal GDM was associated with an increased risk of hyperlipidemia in the offspring during early childhood aged from 3 to 9years old.

1079-P: Maternal Gestational Diabetes and Childhood Hyperlipidemia

Very few studies have assessed the impact of maternal gestational diabetes mellitus (GDM) on lipid profiles in the offspring in China. We aim to compare the lipid profile between children exposed to maternal GDM and those not exposed, and assess association between maternal GDM and offspring’s dyslipidemia risk. We recruited 1144 mother-child pairs (572 GDM and 572 non-GDM women matched by their offspring’s age and sex). We used general linear models to compare mean values of different lipid profiles among children born to mothers with and without GDM. Logistic regression models were used to assess associations of GDM with abnormal lipid profiles in offspring. After adjustment for maternal and children’s characteristics, children born to mothers with GDM had lower mean values of high-density-lipoprotein (HDL) cholesterol (1.40±0.01 vs. 1.50±0.01; P &amp;lt;0.05) and higher mean levels of triglycerides/HDL cholesterol ratio (0.37±0.01 vs. 0.35±0.01; P &amp;lt;0.05) in comparison with their counterparts born to mothers without GDM. Multivariate-adjusted odds ratios among children exposed to mothers with GDM compared with the counterparts were 2.07 (95% confidence interval [CI 1.13-3.79]) for low HDL cholesterol and 1.36 (95% CI 1.01-1.82) for high triglycerides/HDL cholesterol ratio, respectively. Exposure to GDM mothers was an independent risk factor for the abnormal lipid profile among children, which can emerge as early as in the preschool period. Disclosure G. Hu: None. Funding Tianjin Women’s and Children’s Health Center; Tianjin Public Health Bureau; European Foundation for the Study of Diabetes/Chinese Diabetes Society/Lilly Programme for Collaborative Research; National Institute of Diabetes and Digestive and Kidney Diseases