Maternal Gestational Diabetes Mellitus Status Research Articles

Epigenetics of the non-coding RNA nc886 across blood, adipose tissue and skeletal muscle in offspring exposed to diabetes in pregnancy

BackgroundDiabetes in pregnancy is associated with increased risk of long-term metabolic disease in the offspring, potentially mediated by in utero epigenetic variation. Previously, we identified multiple differentially methylated single CpG sites in offspring of women with gestational diabetes mellitus (GDM), but whether stretches of differentially methylated regions (DMRs) can also be identified in adolescent GDM offspring is unknown. Here, we investigate which DNA regions in adolescent offspring are differentially methylated in blood by exposure to diabetes in pregnancy. The secondary aim was to characterize the RNA expression of the identified DMR, which contained the nc886 non-coding RNA.MethodsTo identify DMRs, we employed the bump hunter method in samples from young (9–16 yr, n = 92) offspring of women with GDM (O-GDM) and control offspring (n = 94). Validation by pyrosequencing was performed in an adult offspring cohort (age 28–33 years) consisting of O-GDM (n = 82), offspring exposed to maternal type 1 diabetes (O-T1D, n = 67) and control offspring (O-BP, n = 57). RNA-expression was measured using RT-qPCR in subcutaneous adipose tissue and skeletal muscle.ResultsOne significant DMR represented by 10 CpGs with a bimodal methylation pattern was identified, located in the nc886/VTRNA2-1 non-coding RNA gene. Low methylation status across all CpGs of the nc886 in the young offspring was associated with maternal GDM. While low methylation degree in adult offspring in blood, adipose tissue, and skeletal muscle was not associated with maternal GDM, adipose tissue nc886 expression was increased in O-GDM compared to O-BP, but not in O-T1D. In addition, adipose tissue nc886 expression levels were positively associated with maternal pre-pregnancy BMI (p = 0.006), but not with the offspring’s own adiposity.ConclusionsOur results highlight that nc886 is a metastable epiallele, whose methylation in young offspring is negatively correlated with maternal obesity and GDM status. The physiological effect of nc886 may be more important in adipose tissue than in skeletal muscle. Further research should aim to investigate how nc886 regulation in adipose tissue by exposure to GDM may contribute to development of metabolic disease.

Role of one-carbon nutrient intake and diabetes during pregnancy in children's growth and neurodevelopment: A 2-year follow-up study of a prospective cohort

Background & AimsBoth maternal metabolic dysregulation, e.g., gestational diabetes mellitus (GDM), and maternal supply of nutrients that participate in one-carbon (1C) metabolism, e.g., folate, choline, betaine, and vitamin B12, have been demonstrated to influence epigenetic modification such as DNA methylation, thereby exerting long-lasting impacts on growth and development of offspring. This study aimed to determine how maternal 1C nutrient intake was associated with DNA methylation and further, development of children, as well as whether maternal GDM status modified the association in a prospective cohort. MethodsIn this study, women with (n = 18) and without (n = 20) GDM were recruited at 25-33 weeks gestation. Detailed dietary intake data was collected by 3-day 24-hour dietary recall and nutrient levels in maternal blood were also assessed at enrollment. The maternal-child dyads were invited to participate in a 2-year follow-up during which anthropometric measurement and the Bayley Scales of Infant and Toddler Development™ Screening Test (Third Edition) were conducted on children. The association between maternal 1C nutrients and children’s developmental outcomes was analyzed with a generalized linear model controlling for maternal GDM status. ResultsWe found that children born to mothers with GDM had lower scores in the language domain of the Bayley test (p = 0.049). Higher maternal food folate and choline intakes were associated with better language scores in children (p = 0.01 and 0.025, respectively). Higher maternal food folate intakes were also associated with better cognitive scores in children (p = 0.002). Higher 1C nutrient intakes during pregnancy were associated with lower body weight of children at 2 years of age (p < 0.05). However, global DNA methylation of children’s buccal cells was not associated with any maternal 1C nutrients. ConclusionsIn conclusion, higher 1C nutrient intake during pregnancy was associated with lower body weight and better neurodevelopmental outcomes of children. This may help overcome the lower language scores seen in GDM-affected children in this cohort. Studies in larger cohorts and with a longer follow-up duration are needed to further delineate the relationship between prenatal 1C nutrient exposure, especially in GDM-affected pregnancies, and offspring health outcomes.

Interaction and Metabolic Pathways: Elucidating the Role of Gut Microbiota in Gestational Diabetes Mellitus Pathogenesis.

Gestational diabetes mellitus (GDM) is a complex metabolic condition during pregnancy with an intricate link to gut microbiota alterations. Throughout gestation, notable shifts in the gut microbial component occur. GDM is marked by significant dysbiosis, with a decline in beneficial taxa like Bifidobacterium and Lactobacillus and a surge in opportunistic taxa such as Enterococcus. These changes, detectable in the first trimester, hint as the potential early markers for GDM risk. Alongside these taxa shifts, microbial metabolic outputs, especially short-chain fatty acids and bile acids, are perturbed in GDM. These metabolites play pivotal roles in host glucose regulation, insulin responsiveness, and inflammation modulation, which are the key pathways disrupted in GDM. Moreover, maternal GDM status influences neonatal gut microbiota, indicating potential intergenerational health implications. With the advance of multi-omics approaches, a deeper understanding of the nuanced microbiota-host interactions via metabolites in GDM is emerging. The reviewed knowledge offers avenues for targeted microbiota-based interventions, holding promise for innovative strategies in GDM diagnosis, management, and prevention.

PsyNBIOsis: Investigating the Association between Maternal Gestational Diabetes, Mental Health, Diet and Childhood Obesity Risk: Protocol for a Prospective, Longitudinal, Observational Study.

Gestational diabetes mellitus (GDM) is associated with poorer maternal mental health (depression and anxiety). Maternal mental health and GDM are likely to influence diet, which in turn impacts the course of GDM. Maternal diet may also be directly or indirectly associated with changes in infant anthropometry. The aims of this study are to (1) examine the associations between maternal GDM, mental health and diet, and (2) evaluate the associations between these maternal factors, breastmilk composition and infant anthropometry. This prospective, observational, longitudinal cohort study compares a cohort of women with and without GDM. Maternal mental health and diet are assessed using validated questionnaires. Breastmilk composition is measured with the Human Milk Analyzer, and infant body composition is measured with air displacement plethysmography. Once data have been collected, PsyNBIOsis will provide evidence for the associations between maternal mental health, GDM status and diet, and their impact on breastmilk composition and early infant growth. The results may inform the Developmental Origins of Health and Disease framework and provide data on which to build cost-effective interventions to prevent both the development of mental health issues in mothers and adverse growth patterns in infants.

Maternal high body mass index, but not gestational diabetes, is associated with poorer educational attainment in mid-childhood

Previous studies suggest that gestational diabetes mellitus (GDM) is associated with poorer cognitive outcomes in children, however confounding factors especially maternal BMI have been poorly accounted for. This study aimed to examine the independent associations between maternal BMI, GDM status and educational outcomes. Antenatal data from a prospective birth cohort (Pregnancy Outcome Prediction Study; POPS, 2008-2012, Cambridge, UK) was linked to mid-childhood educational outcomes (Department for Education, UK). 3249 children born at term were stratified by maternal GDM status and BMI at booking (<25 kg/m2 vs. ≥25 kg/m2). Regression models adjusted for relevant maternal, child, and socioeconomic factors were used to determine associations with academic outcomes at ages 5-7. No differences in educational attainment found between children exposed to GDM vs. non-exposed children. Neither maternal glucose levels measured at 11-14 weeks, 24-28 weeks, or acceleration of the fetal abdominal circumference growth velocity were related to educational attainment between ages 5-7. Children of mothers with booking BMI ≥25kg/m2 vs. <25kg/m2 were ∼50% more likely not to meet expected educational standards regardless of GDM status (Age 5: aOR 1.44; 95%CI 1.19-1.74, p<0.001; Age 6: aOR 1.61; 95%CI 1.28-2.02, p<0.001). The association between maternal BMI and offspring educational attainment is dose-dependent and robust to stratification by GDM status and adjustment for socio-economic factors. Mid-childhood educational attainment is not associated with maternal glucose status and this may provide important reassurance for pregnant women and clinicians. However maternal BMI is associated with lower childhood educational attainment and may be modifiable with intervention before or during pregnancy.

Leptin resistance in children with in utero exposure to maternal obesity and gestational diabetes.

Leptin resistance occurs with obesity, but it is unknown if individuals at risk for obesity develop leptin resistance prior to obesity. Investigate whether leptin resistance is independent of weight status in children at risk for obesity due to intrauterine exposure to maternal obesity or gestational diabetes mellitus (GDM). Mother-child dyads (N = 179) were grouped by maternal pregnancy weight and GDM status: (1) normal weight, no GDM; (2) overweight/obesity, no GDM; (3) overweight/obesity with GDM. Children (4-10 years) were further stratified by current body mass index (BMI) <85th or ≥85th percentile. Leptin resistance of children and mothers was calculated as fasting leptin/fat mass index. Two-way ANOVA was used to assess whether leptin concentrations and leptin resistance differed by current weight status or in utero exposure group, after adjusting for race, sex and Tanner stage. Children with a BMI ≥85th percentile had more leptin resistance than those with a BMI <85th percentile (p < 0.001), but leptin resistance did not differ by in utero exposure. Similarly, leptin resistance in women was associated with weight status and not prior GDM. Results suggest that leptin concentrations are associated with obesity but not risk for obesity based on in utero exposure to maternal obesity or GDM.

A nutritional supplement taken during preconception and pregnancy influences human milk macronutrients in women with overweight/obesity and gestational diabetes mellitus.

Maternal overweight/obesity and gestational diabetes mellitus (GDM) are associated with an increased risk of their offspring developing overweight/obesity or type 2 diabetes later in life. However, the impacts of maternal overweight/obesity and dysglycemia on human milk (HM) macronutrient composition are not well understood. Through a double-blind randomised controlled trial, we investigated the effects of maternal supplementation from preconception throughout pregnancy until birth on HM macronutrient concentrations, in association with maternal and infant factors including maternal pre-pregnancy body mass index (BMI) and GDM status. In addition, we aimed to characterise longitudinal changes in HM macronutrients. The control supplement contained calcium, iodine, iron, β-carotene, and folic acid. The intervention supplement additionally contained zinc, vitamins B2, B6, B12, and D3, probiotics, and myo-inositol. HM samples were collected across seven time points from 1 week to 12 months from Singapore and/or New Zealand. HM macronutrient concentrations were measured using a MIRIS Human Milk Analyser. Potential differences in HM macronutrient concentrations were assessed using linear mixed models with a repeated measures design. Overall, HM macronutrient concentrations were similar between control and intervention groups. Among the control group, overweight/obesity and GDM were associated with higher HM fat and energy concentrations over the first 3 months. Such associations were not observed among the intervention group. Of note, mothers with GDM in the intervention group had lower HM fat by 10% (p = 0.049) and energy by 6% (p = 0.029) than mothers with GDM in the control group. Longitudinal changes in HM macronutrient concentrations over 12 months of lactation in New Zealand showed that HM fat and energy decreased in the first 6 months then increased until 12 months. HM lactose gradually decreased from 1 week to 12 months while crude protein decreased from 1 week to 6 months then remained relatively constant until 12 months of lactation. Maternal overweight/obesity or GDM were associated with increased HM fat and energy levels. We speculate the intervention taken during preconception and pregnancy altered the impact of maternal BMI or GDM status on HM macronutrient composition. Further studies are required to identify the mechanisms underlying altered HM macronutrient concentration in the intervention group and to determine any long-term effects on offspring health. ClinicalTrials.gov, NCT02509988, Universal Trial Number U1111-1171-8056. Registered on 16 July 2015. This is an academic-led study by the EpiGen Global Research Consortium.

Maternal Gestational Diabetes Is Associated with High Risk of Childhood Overweight and Obesity: A Cross-Sectional Study in Pre-School Children Aged 2–5 Years

Background and Objectives: Childhood obesity is a global public health concern with long-term and serious health implications. An important factor for childhood obesity is maternal gestational diabetes mellitus (GDM), which in turn impacts maternal and offspring long-term health. This study aimed to investigate the associations between maternal GDM and childhood weight status and multiple anthropometric and sociodemographic factors and perinatal outcomes. Materials and Methods: A total of 5348 children aged 2-5 years old and their paired mothers took part in the study. Questionnaires were utilized to evaluate the sociodemographic factors and perinatal outcomes as well as smoking habits, educational level, economic status, age, and parity status. Children's anthropometric parameters were measured, and maternal medical history, preterm birth records, and anthropometric measures during pregnancy were retrieved by their medical records. Results: Overall, 16.4% of the children aged at 2-5 years were overweight, and 8.2% of them were affected by obesity, leading to a total 24.6% of children with overweight/obesity. Further, 5.5% of the enrolled mothers were diagnosed with gestational diabetes mellitus. GDM doubles the probability of childhood overweight/obesity at ages 2-5 years old independently of multiple confounding factors. Pre-pregnancy overweight and obesity, older maternal age, and smoking are risk factors for GDM, while GDM additionally increases the risk of preterm birth. Children of mothers that developed GDM were at greater risk of overweight or obesity, with the association between GDM and offspring's weight status being independent of confounding factors. Conclusions: GDM is a severe public health issue with prolonged complications for both the mother and their children. Public health approaches and programs need to promote the negative role of pre-pregnancy weight and smoking status as well as the significance of a good glycemic control throughout gestation in women of childbearing age.

Prolactin in relation to gestational diabetes and metabolic risk in pregnancy and postpartum: A systematic review and meta-analysis.

Pre-clinical evidence suggests that prolactin has important metabolic functions in pregnancy and postpartum, in addition to lactogenic actions. To explore the relationship between prolactin and maternal metabolic outcomes in human pregnancy and postpartum, particularly in relation to gestational diabetes mellitus (GDM). MEDLINE via OVID, CINAHL plus, Embase. Eligible studies included women who were pregnant or up to 12 months postpartum, reporting at least one maternal serum prolactin level in relation to key metabolic outcomes including GDM, glycaemic parameters, obesity, and gestational weight gain. Two independent reviewers extracted data. Twenty-six articles were included. Meta-analysis showed no relationship between maternal prolactin levels and GDM status, with a weighted mean difference of -2.14 ng/mL (95% CI -12.54 to 8.27 ng/mL, p=0.7) between GDM and controls in early pregnancy (n=3 studies) and -3.89 ng/mL (95% CI, -15.20 to 7.41 ng/mL, p=0.5) in late pregnancy (n=11 studies). In narrative synthesis of other outcomes (due to study heterogeneity and/or lack of data), prolactin levels were not associated with maternal glycaemic or weight-related parameters during pregnancy, but in the postpartum period (particularly with lactation) a high-prolactin environment was associated with low circulating insulin and beta-cell function, and increased insulin sensitivity. Current evidence from human studies does not clearly support a relationship between prolactin and metabolic parameters during pregnancy, including with GDM status. Elevated prolactin was associated with lower insulin and beta-cell function and higher insulin sensitivity in the post-partum period, but the direction of causality remains unclear. https://www.crd.york.ac.uk/prospero/, identifier [CRD42021262771].

Influences of gestational diabetes mellitus on the oral microbiota in offspring from birth to 1 month old

BackgroundMaternal gestational diabetes mellitus (GDM) had long-term influences on the health of their children. However, the influences of GDM on the oral microbiota, which was closely related to oral and systemic health in offspring, were less documented. The present study aimed to explore the oral microbiota of neonates born to mothers with GDM is differentially colonized compared with those born to mothers without GDM, and whether any such differences persist to 1 month of age.MethodsOral samples were collected from children of mothers with (n = 20) and without GDM (n = 34) at birth and again at an average age of 1 month. The oral microbiota was characterized by 16S rRNA sequencing (V3-V4). Differences in diversity and composition according to maternal GDM status were assessed, and different metabolic functional pathways and microbial ecological networks were also analyzed.ResultsAlthough no significant differences were observed in diversity metrics between GDM and non-GDM groups (P > 0.05), we found significant differences in the taxonomic composition of oral microbiota from phylum to genus level between the two groups, with the GDM group exhibiting less abundance of Veillonella in both “Day 1” (P < 0.001) and “Day 30” (P < 0.05) phases. Metabolic pathways analysis showed that 5-aminoimidazole ribonucleotide biosynthesis and inosine-5'-phosphate biosynthesis were enriched in GDM subjects in the “Day 30” phase. Moreover, ecological network analysis revealed apparent differences between GDM and control groups, with the non-GDM group containing more high-degree nodes and microbial interactions compared with the GDM group.ConclusionMaternal GDM was associated with an altered oral microbial composition in neonates, although the distinct difference between GDM and non-GDM groups diminished in infancy. The oral microbiota functions and ecological networks differed dramatically between the two groups, highlighting the importance of maternal GDM status on initial oral microbiota in offspring.

Selective morphological and volumetric alterations in the hippocampus of children exposed in utero to gestational diabetes mellitus.

Prior epidemiological studies have found that in utero exposure to gestational diabetes mellitus (GDM) is associated with increased risk for neurodevelopmental disorders. However, brain alterations associated with GDM are not known. The hippocampus is pivotal for cognition and emotional regulation. Therefore, we assessed relationships between in utero exposure to GDM and hippocampal morphology and subfield structure during childhood. One hundred seventeen children aged 7–11 years (57% girls, 57% exposed to GDM), born at Kaiser Permanente Southern California, participated in the BrainChild Study. Maternal GDM status was determined from electronic medical records. Children underwent brain magnetic resonance imaging. Freesurfer 6.0 was used to measure hippocampal and individual hippocampal subfield gray matter volume (mm3). Morphological analyses on the hippocampal surface were carried out using shape analysis. GDM‐exposed children exhibited reduced radial thickness in a small, spatially‐restricted portion of the left inferior body of the hippocampus that corresponds to the CA1 subfield. There was a significant interaction between GDM‐exposure and sex on the right hippocampal CA1 subfield. GDM‐exposed boys had reduced right CA1 volume compared to unexposed boys, but this association was no longer significant after controlling for age. No significant group differences were observed in girls. Our results suggest that GDM‐exposure impacts shape of the left hippocampal CA1 subfield in both boys and girls and may reduce volume of right hippocampal CA1 only in boys. These in‐depth findings illuminate the unique properties of the hippocampus impacted by prenatal GDM‐exposure and could have important implications for hippocampal‐related functions.

Association of gestational diabetes mellitus with offspring weight status across infancy: a prospective birth cohort study in China

BackgroundThe association between gestational diabetes mellitus (GDM) and childhood body weight remains controversial, and additional study is needed, especially in Asian populations.MethodsThis prospective study investigated the association between maternal glucose concentration, and GDM status and infant body weight from birth to 12 months of age. Linear mixed effects (LME) models and multiple linear regression were used to assess the longitudinal association of GDM with infant growth measured by weight-for-length z-scores (WFLZ), weight-for-age z-scores (WFAZ), and length-for-age z-scores (LFAZ) at birth, 1, 3, 6, 8, and 12 months of age.ResultsOffspring born to mothers with GDM had higher WFLZ [β: 0.26 SD units (95% CI: 0.13–0.40)] across infancy than those of mothers without GDM. When stratified analysis by maternal pre-pregnancy body mass index (BMI) status, the association was pronounced in normal-weight [β:0.28 SD units (95% CI: 0.11–0.45)] and overweight/obese women [β: 0.34 SD units (95% CI: 0.09–0.58)] but not in underweight women (P for interaction < 0.05). Multiple linear regression found that the effect estimate of GDM on infant WFLZ was highest at birth [β: 0.36 SD units (95% CI: 0.11–0.61)], remained significant at 1 [β: 0.22 SD units (95% CI: 0.03–0.41)] and 3 [β:0.19 SD units (95% CI: 0.01–0.37)] months of age and decreased across infancy. Maternal GDM status was not associated with infant WFAZ or LFAZ.ConclusionsMaternal GDM status was associated with infant WFLZ, but not WFAZ or LFAZ. The association between GDM status and offspring WFLZ was more pronounced in early infancy or in normal-weight and overweight/obese women. Increased public health efforts to prevent GDM in normal-weight and overweight/obese pre-pregnancy mothers are recommended to control offspring overweight or obesity.

Placental maternally expressed gene3 differentially methylated region methylation profile is associated with maternal glucose concentration and newborn birthweight.

Aims/IntroductionEmerging evidence shows that epigenetic modifications occurring during fetal development in response to intrauterine exposures could be one of the mechanisms involved in the early determinants of adult metabolic disorders. This study aimed to investigate whether the placental maternally expressed gene 3 (MEG3) deoxyribonucleic acid (DNA) methylation profile is associated with maternal gestational diabetes mellitus status and newborn birthweight.Materials and MethodsSamples for measurement were collected from 23 women with gestational diabetes mellitus and 23 healthy controls. MEG3 gene expression and DNA methylation levels were assessed using quantitative real‐time polymerase chain reaction and MethylTargetTM, respectively. Pearson correlation analyses were used to examine associations between placental DNA methylation levels and clinical variables of interest. The associated results were adjusted by multivariate linear regression for maternal age, body mass index, height, gestational age and newborn sex as confounders.ResultsWe found that the DNA methylation levels in the MEG3 differentially methylated region were significantly different between the gestational diabetes mellitus and control groups on the maternal side of the placenta (40.64 ± 2.15 vs 38.33 ± 2.92; P = 0.004). Furthermore, the mean MEG3 DNA methylation levels were correlated positively with maternal fasting glucose concentrations (R = 0.603, P < 0.001) and newborn birthweight (R = 0.568, P < 0.001).ConclusionsThe placental DNA methylation status in the MEG3 differentially methylated region was correlated with maternal glucose concentrations and newborn birthweight. These epigenetic adaptations might contribute to late‐onset obesity, underlining the adverse intrauterine environment.

Comparative Studies of the Gut Microbiota in the Offspring of Mothers With and Without Gestational Diabetes.

Background: Offspring of mothers with gestational diabetes mellitus (GDM) have increased risk of developing metabolic disorders as they grow up. Microbial colonization of the newborn gut and environmental exposures affecting the configuration of the gut microbiota during infancy have been linked to increased risk of developing disease during childhood and adulthood. In a convenience sample, we examined whether the intestinal tract of children born to mothers with GDM is differentially colonized in early life compared to offspring of mothers with normal gestational glucose regulation. Secondly, we examined whether any such difference persists during infancy, thus potentially conferring increased risk of developing metabolic disease later in life.Methods: Fecal samples were collected from children of mothers with (n = 43) and without GDM (n = 82) during the first week of life and again at an average age of 9 months. The gut microbiota was characterized by 16S rRNA gene amplicon sequencing (V1–V2). Differences in diversity and composition according to maternal GDM status were assessed, addressing potential confounding by mode of delivery, perinatal antibiotics treatment, feeding and infant sex.Results: Children of mothers with GDM were featured by a differential composition of the gut microbiota, both during the first week of life and at 9 months, at higher taxonomic and OTU levels. Sixteen and 15 OTUs were differentially abundant after correction for multiple testing during the first week of life and at 9 months, respectively. Two OTUs remained differentially abundant after adjustment for potential confounders both during the first week of life and at 9 months. Richness (OTU) was decreased in neonates born to mothers with GDM; however, at 9 months no difference in richness was observed. There was no difference in Shannon's diversity or Pielou's evenness at any timepoint. Longitudinally, we detected differential changes in the gut microbiota composition from birth to infancy according to GDM status.Conclusion: Differences in glycaemic regulation in late pregnancy is linked with relatively modest variation in the gut microbiota composition of the offspring during the first week of life and 9 months after birth.

Maternal Gestational Diabetes Mellitus Modifies the Relationship Between Genetically Determined Body Mass Index During Pregnancy and Childhood Obesity

ObjectiveTo analyze the interactions between maternal gestational diabetes mellitus (GDM) and genetically determined maternal body mass index (BMI) during pregnancy on offspring childhood obesity. Research Design and MethodsA total of 1114 Chinese mother-child pairs (560 GDM and 554 non-GDM) were included between August 2009 and July 2011. Maternal genetic risk score (GRS) of BMI during pregnancy was derived on the basis of 12 single nucleotide polymorphisms identified from a genome-wide association study. Offspring’s BMI, BMI-for-age z score, weight, weight-for-age z score, waist circumference, sum of skinfolds, and body fat percentage during childhood were measured or calculated. ResultsMaternal GRS of BMI during pregnancy significantly interacted with maternal GDM status on childhood risks of overweight and obesity (all P for interaction <.05). After multivariable adjustment, per unit of GRS was associated with a 24% (P<.001) and a 28% (P<.001) increased risk of overweight and obesity among children of GDM mothers, whereas no significant associations were observed among children of mothers without GDM. In addition, per unit GRS of BMI during pregnancy was significantly associated with 0.16 kg/m2 higher BMI (P=.002), 0.09 higher BMI-for-age z score (P=.002), 0.24 kg higher weight (P=.04), 0.06 higher weight-for-age z score (P=.02), 0.28 cm higher waist circumference (P=.03), 0.94 mm higher sum of skinfolds (P=.004), and 0.37% higher body fat percentage (P=.03) among children of GDM mothers. There were no significant associations between maternal GRS of BMI during pregnancy and offspring’s obesity-related outcomes among children of mothers without GDM. ConclusionOur findings for the first time indicate that maternal GDM status may modify the relation between genetically determined maternal BMI during pregnancy and offspring’s obesity risk during childhood.

Contributions of Prenatal Exposures and Child Lifestyle to Insulin Sensitivity.

Prenatal exposures and lifestyle factors are important for metabolic health. Determine how prenatal exposures to maternal obesity and/or gestational diabetes mellitus (GDM) and childhood lifestyle factors independently contribute to child insulin sensitivity. Ninety children aged 7 to 11 years (56% girls, 60% exposed to GDM), born at Kaiser-Permanente Southern California, completed an oral glucose tolerance test (OGTT) as part of the BrainChild Study. Matsuda insulin sensitivity index (ISI) was used to estimate insulin sensitivity. Participants completed two 24-hour dietary recalls, and daily energy intake (EI), dietary added sugar, and total sugar were calculated. The 3-day physical activity recall determined the average minutes per day of moderate to vigorous physical activity (MVPA) and the average minutes per day spent sedentary. Maternal prepregnancy body mass index (BMI) and GDM status were extracted from electronic medical records. Matsuda-ISI. Linear regression showed that children who spent more time in MVPA had better ISI (β = 0.33; P = 0.001), and results remained after adjustment for maternal prepregnancy BMI, GDM exposure, child age, sex, daily EI, dietary added sugar (β = 0.34; P = 0.001), and further adjustment for child adiposity (β = 0.29; P = 0.001). Time spent sedentary, maternal prepregnancy BMI, GDM exposure, dietary added sugar, total sugar, and EI were not associated with ISI. Physical activity was the only predictor of ISI at this age, suggesting that engaging in physical activity during childhood is beneficial for insulin sensitivity and may ameliorate future risk for metabolic disease.

Altered growth trajectory in children born to mothers with gestational diabetes mellitus and preeclampsia.

Gestational diabetes mellitus (GDM) and preeclampsia are leading causes of mortality and morbidity in mothers and children. High childhood body mass index (BMI) is among their myriad of negative outcomes. However, little is known about the trajectory of the child BMI exposed to GDM and co-occurring preeclampsia from early to mid-childhood. This study examined the independent and joint impact of GDM and preeclampsia on childhood BMI trajectory. A population-based sample of 356 mothers were recruited from OB/GYN clinics in New York. Their children were then followed annually from 18 to 72months. Maternal GDM and preeclampsia status were obtained from medical records. Child BMI was calculated based on their height and weight at annual visits. Hierarchical Linear Modeling was used to evaluate the trajectories of child BMI exposed to GDM and preeclampsia. BMI trajectory by GDM decreased (t ratio = - 2.24, [Formula: see text]0.45, 95% CI - 0.05-0.95, p = 0.07), but the trajectory by preeclampsia increased over time (t ratio = 3.153,[Formula: see text]0.65, 95% CI 0.11-1.18, p = 0.002). Moreover, there was a significant interaction between the two (t ratio = -2.24, [Formula: see text]- 1.244, 95% CI 0.15-2.33, p = 0.02), such that the BMI of children born to mothers with both GDM and preeclampsia showed consistent increases over time. GDM and preeclampsia could be used as a marker for childhood obesity risk and the identification of a high-risk group, providing potential early intervention. These findings highlight the importance of managing obstetric complications, as an effective method of child obesity prevention.

196-LB: Prenatal and Lifestyle Contributions to Child Insulin Sensitivity

Background: Early life exposures play an important role in metabolic health throughout life. We examined how prenatal exposures to maternal obesity or gestational diabetes mellitus (GDM) and low levels of physical activity and increased food intake may contribute to reductions in insulin sensitivity in childhood. Methods: Participants were 7-10 year old children who were born at Kaiser Permanente Southern California. Maternal pre-pregnancy BMI and GDM status were extracted from electronic medical records. Child weight and height were measured, and oral glucose tolerance tests were performed. Insulin sensitivity was estimated using the Matsuda insulin sensitivity index (ISI). Diet was assessed using 24-hour dietary recalls and daily energy intake (EI) was calculated. Physical activity was assessed using a 3-day physical activity recall and average min/day of moderate to vigorous physical activity (MVPA) was calculated. Linear regression was used to assess ISI associations with the exposures. Results: 92 children (52 girls; 40 boys; 55 GDM-exposed; 37 unexposed) participated. Maternal pre-pregnancy BMI ranged from 19.0-50.4 kg/m2. Mean±SD child age was 8.3±0.9 years, BMI z-score: 0.60±1.1, ISI: 10.6±5.9, EI: 1790.7±444.2 kcal, and MVPA: 118.7±93.8 min/day. Children who spent more time in MVPA had better insulin sensitivity (β=0.82; P=.02). Adjusting for maternal pre-pregnancy BMI, GDM exposure, child age, sex, and EI, did not affect this relationship (β=0.87; P&amp;lt;.01), nor did further adjusting for BMI z-score (β=0.78; P=.01). Prenatal exposure to GDM and child ISI (β=0.19, P=.28) and maternal pre-pregnancy BMI were not significantly associated with child ISI (β=-0.01, P=0.40), nor was child’s EI associated with ISI (β=0.001; P=.59). Conclusions: Time spent in MVPA was the strongest predictor of child insulin sensitivity. Our findings suggest that engaging in MVPA during childhood is beneficial for insulin sensitivity and may help ameliorate future risk for metabolic disease. Disclosure J. Alves: None. T. Chow: None. J. Zink: None. S. Luo: None. M.P. Martinez: None. A. Romero: None. A. Xiang: None. K.A. Page: None. Funding American Diabetes Association (1-14-ACE-36 to K.A.P.); National Institutes of Health (1F31MH115640-01A1)

An Unbiased Lipidomics Approach Identifies Early Second Trimester Lipids Predictive of Maternal Glycemic Traits and Gestational Diabetes Mellitus.

To investigate the relationship between early second trimester serum lipidomic variation and maternal glycemic traits at 28 weeks and to identify predictive lipid biomarkers for gestational diabetes mellitus (GDM). Prospective study of 817 pregnant women (discovery cohort, n = 200; validation cohort, n = 617) who provided an early second trimester serum sample and underwent an oral glucose tolerance test (OGTT) at 28 weeks. In the discovery cohort, lipids were measured using direct infusion mass spectrometry and correlated with OGTT results. Variable importance in projection (VIP) scores were used to identify candidate lipid biomarkers. Candidate biomarkers were measured in the validation cohort using liquid chromatography-mass spectrometry and tested for associations with OGTT results and GDM status. Early second trimester lipidomic variation was associated with 1-h postload glucose levels but not with fasting plasma glucose levels. Of the 13 lipid species identified by VIP scores, 10 had nominally significant associations with postload glucose levels. In the validation cohort, 5 of these 10 lipids had significant associations with postload glucose levels that were independent of maternal age and BMI, i.e., TG(51.1), TG(48:1), PC(32:1), PCae(40:3), and PCae(40:4). All except the last were also associated with maternal GDM status. Together, these four lipid biomarkers had moderate ability to predict GDM (area under curve [AUC] = 0.71 ± 0.04, P = 4.85 × 10-7) and improved the prediction of GDM by age and BMI alone from AUC 0.69 to AUC 0.74. Specific early second trimester lipid biomarkers can predict maternal GDM status independent of maternal age and BMI, potentially enhancing risk factor-based screening.

Exposure to Gestational Diabetes Mellitus: Impact on the Development of Early-Onset Type 2 Diabetes in Canadian First Nations and Non-First Nations Offspring.

Type 2 diabetes is increasing in children worldwide, with Canadian First Nations (FN) children disproportionally affected. The prevalence of gestational diabetes mellitus (GDM) also is increasing. The objective of this study was to evaluate the impact of GDM exposure in utero and FN status on the subsequent risk of type 2 diabetes in offspring in the first 30 years of life. In this population-based historical prospective cohort study, we used administrative databases linked to a clinical database to explore the independent association and interaction between GDM and FN status on the subsequent development of type 2 diabetes in offspring. Among 321,008 births with a median follow-up of 15.1 years, both maternal GDM and FN status were independently associated with subsequent risk of type 2 diabetes in offspring in the first 30 years of life (hazard ratio 3.03 [95% CI 2.44-3.76; P < 0.0001] vs. 4.86 [95% CI 4.08-5.79; P < 0.0001], respectively). No interaction between GDM and FN status on type 2 diabetes risk was observed. FN status had a stronger impact on the development of type 2 diabetes in offspring than GDM. GDM is an important modifiable risk factor for type 2 diabetes, and its prevention may reduce the prevalence of subsequent type 2 diabetes in offspring. This study adds unique and rigorous evidence to the global public health debate about the impact of GDM on the long-term health of offspring.