Maternal Glucose Concentrations in Early Pregnancy and Cardiometabolic Risk Factors in Childhood

Wahab, Rama J.; Voerman, Ellis; Jansen, Pauline W.; Oei, Edwin H.G.; Steegers, Eric A.P.; Jaddoe, Vincent W V; Gaillard, Romy

doi:10.1002/oby.22771

Cited by 17 publications

(22 citation statements)

References 45 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Maternal glucose concentrations were not associated with DNA methylation levels at the two identified CpGs in peripheral blood of 10-year-old children (p values > 0.1) (Additional file 7: Table S8). In exploratory analyses, the two identified CpGs were not associated with birth weight or childhood glucose concentrations, which both were previously found to be associated with maternal early-pregnancy glucose concentrations in our data (p values > 0.1) [9,13].…”

Section: Associations Of Maternal Early-pregnancy Glucose and Insulinsupporting

confidence: 45%

“…It has been suggested that women who develop gestational diabetes or hyperglycemia later in pregnancy already have suboptimal glucose metabolism before or in early pregnancy [43,44]. Maternal glycemic measures in early pregnancy have been described to be associated with altered fetal growth and glucose metabolism in childhood, but not with child adiposity, lipid levels, and blood pressure after adjustment for maternal pre-pregnancy BMI [9,12,13]. Thus, early pregnancy may already be a critical period for the effects of maternal glucose concentrations on offspring birth outcomes and glycemic health in childhood.…”

Section: Interpretation Of Main Findingsmentioning

confidence: 99%

“…Exploratory analyses were performed in the relevant strata of maternal BMI to examine associations of identified CpGs with offspring birth weight and childhood glucose concentrations measured at age 10 years. We chose these outcomes because we have previously found them to be associated with maternal early-pregnancy glucose concentrations [9,13]. We ran linear regression models using gestational age and sex-adjusted birth weight standard deviation scores (SDS) and childhood glucose concentrations as outcomes.…”

Section: Associations Of Identified Cpgs With Offspring Health Outcomesmentioning

confidence: 99%

“…As such, impaired maternal glucose metabolism may already exert negative effects in that early stage. Early-pregnancy glucose metabolism has been shown to be associated with altered fetal growth, adverse birth outcomes, and childhood glucose metabolism, but not with other childhood cardiometabolic outcomes after adjusting for maternal pre-pregnancy BMI [ 9 , 12 , 13 ]. Thus, early pregnancy may be an important time window for the effects of suboptimal maternal glycemic measures and as such an influential period for future interventions.…”

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Associations of maternal early-pregnancy blood glucose and insulin concentrations with DNA methylation in newborns

et al. 2020

Self Cite

View full text Add to dashboard Cite

Background Intrauterine exposure to a disturbed maternal glucose metabolism is associated with adverse offspring outcomes. DNA methylation is a potential mechanism underlying these associations. We examined whether maternal early-pregnancy glucose and insulin concentrations are associated with newborn DNA methylation. In a population-based prospective cohort study among 935 pregnant women, maternal plasma concentrations of non-fasting glucose and insulin were measured at a median of 13.1 weeks of gestation (95% range 9.4–17.4). DNA methylation was measured using the Infinium HumanMethylation450 BeadChip (Ilumina). We analyzed associations of maternal early-pregnancy glucose and insulin concentrations with single-CpG DNA methylation using robust linear regression models. Differentially methylated regions were analyzed using the dmrff package in R. We stratified the analyses on normal weight versus overweight or obese women. We also performed a look-up of CpGs and differently methylated regions from previous studies to be associated with maternal gestational diabetes, hyperglycemia or hyperinsulinemia, or with type 2 diabetes in adults. Results Maternal early-pregnancy glucose and insulin concentrations were not associated with DNA methylation at single CpGs nor with differentially methylated regions in the total group. In analyses stratified on maternal BMI, maternal early-pregnancy glucose concentrations were associated with DNA methylation at one CpG (cg03617420, XKR6) among normal weight women and at another (cg12081946, IL17D) among overweight or obese women. No stratum-specific associations were found for maternal early-pregnancy insulin concentrations. The two CpGs were not associated with birth weight or childhood glycemic measures (p values > 0.1). Maternal early-pregnancy insulin concentrations were associated with one CpG known to be related to adult type 2 diabetes. Enrichment among nominally significant findings in our maternal early-pregnancy glucose concentrations was found for CpGs identified in a previous study on adult type 2 diabetes. Conclusions Maternal early-pregnancy glucose concentrations, but not insulin concentrations, were associated with DNA methylation at one CpG each in the subgroups of normal weight and of overweight or obese women. No associations were present in the full group. The role of these CpGs in mechanisms underlying offspring health outcomes needs further study. Future studies should replicate our results in larger samples with early-pregnancy information on maternal fasting glucose metabolism.

show abstract

Section: Associations Of Maternal Early-pregnancy Glucose and Insulinsupporting

confidence: 45%

Section: Interpretation Of Main Findingsmentioning

confidence: 99%

Section: Associations Of Identified Cpgs With Offspring Health Outcomesmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Associations of maternal early-pregnancy blood glucose and insulin concentrations with DNA methylation in newborns

et al. 2020

Self Cite

View full text Add to dashboard Cite

show abstract

“…118 This is also reflected in a recent human study in the Generation R birth cohort that reported high maternal insulin concentration in early gestation is associated with increased systolic blood pressure in offspring, although these associations attenuated to non-significance after adjustment for maternal BMI, suggesting that hypertension is programmed by other factors related to maternal weight than hyperinsulinaemia. 119 Future studies in animal models may help to delineate the contribution of maternal circulating factors independent of each other and of maternal BMI.…”

Section: Interventions During Ob E S E/g Dm Preg Nan Cie Smentioning

confidence: 99%

Nutritional and developmental programming effects of insulin

Dearden

Bouret

Ozanne

2021

J Neuroendocrinology

View full text Add to dashboard Cite

The discovery of insulin in 1921 was a major breakthrough in medicine and for therapy in patients with diabetes. The dramatic rise in the prevalence of overweight and obesity has been tightly linked to an increased prevalence of gestational diabetes mellitus (GDM), which poses major health concerns. Babies born to GDM mothers are more likely to develop obesity, type 2 diabetes and cardiovascular disease later in life. Evidence accumulated during the past two decades has revealed that high levels insulin, such as those observed during GDM, can have a widespread effect on the development and function of a variety of organs. This review summarises our current knowledge on the role of insulin in the placenta, cardiovascular system and brain during critical periods of development, as well as how it can contribute to lifelong metabolic regulation. We also discuss possible intervention strategies to ameliorate and hopefully reverse the developmental defects associated with obesity and GDM.

show abstract

Maternal Early‐Pregnancy Glucose Concentrations and Liver Fat Among School‐Age Children

et al. 2021

Self Cite

View full text Add to dashboard Cite

BaCKgRoUND aND aIMS: Gestational diabetes seems to be associated with offspring NAFLD. We hypothesized that maternal glucose concentrations across the full range may have persistent effects on offspring liver fat accumulation.appRoaCH aND ReSUltS: In a multiethnic, populationbased, prospective cohort study among 2,168 women and their offspring, maternal early-pregnancy glucose concentrations were measured at a median of 13.1 weeks' gestation (95% CI, 9.6-17.2). Liver fat fraction was measured at 10 years by MRI. NAFLD was defined as liver fat fraction ≥5.0%. We performed analyses among all mothers with different ethnic backgrounds and those of European ancestry only. The multiethnic group had a median maternal early-pregnancy glucose concentration of 4.3 mmol/L (interquartile range, 3.9-4.9) and a 2.8% (n = 60) prevalence of NAFLD. The models adjusted for child age and sex only showed that in the multiethnic group, higher maternal early-pregnancy glucose concentrations were associated with higher liver fat accumulation and higher odds of NAFLD, but these associations attenuated into nonsignificance after adjustment for potential confounders. Among mothers of European ancestry only, maternal early-pregnancy glucose concentrations were associated with increased odds of NAFLD (OR, 1.95; 95% CI, 1.32; 2.88, after adjustment for confounders) per 1-mmol/L increase in maternal earlypregnancy glucose concentration. These associations were not explained by maternal prepregnancy and childhood body mass index, visceral fat, and metabolic markers. CoNClUSIoNS:In this study, maternal early-pregnancy glucose concentrations were only among mothers of European ancestry associated with offspring NAFLD. The associations of higher maternal early-pregnancy glucose concentrations with offspring NAFLD may differ between ethnic groups. (Hepatology 2021;0:1-12). P re-existing diabetes and gestational diabetes are complicating up to 25% of pregnancies. (1)(2)(3) Recent studies suggest that gestational diabetes leads to impaired offspring cardiovascular and metabolic health in childhood and adulthood. (4)(5)(6)(7) The observed associations seem not to be restricted to the clinical diagnosis of gestational diabetes, but are also present across the full range of maternal glucose concentrations. (8)(9)(10) Previous studies suggest that gestational diabetes is also associated with offspring markers of liver pathology. (11)(12)(13)(14)(15)(16) Results from animal studies suggest that offspring of maternal pregnancy hyperglycemia are predisposed to develop liver steatosis. (13)(14)(15)(16) In humans, a case-control study among 25 mothers showed that intrahepatocellular lipid content, as measured by MR spectroscopy, was increased in neonates of mothers with both obesity and gestational diabetes compared to neonates of mothers with both normal Abbreviations: BMI, body mass index; IDEAL IQ, iterative decomposition of water and fat with echo asymmetry and least squares estimation; SDS, standard deviation score.

show abstract

Maternal Glucose Concentrations in Early Pregnancy and Cardiometabolic Risk Factors in Childhood

Cited by 17 publications

References 45 publications

Associations of maternal early-pregnancy blood glucose and insulin concentrations with DNA methylation in newborns

Associations of maternal early-pregnancy blood glucose and insulin concentrations with DNA methylation in newborns

Nutritional and developmental programming effects of insulin

Maternal Early‐Pregnancy Glucose Concentrations and Liver Fat Among School‐Age Children

Contact Info

Product

Resources

About