scholarly journals Dichotomy in the Impact of Elevated Maternal Glucose Levels on Neonatal Epigenome

Author(s):  
Ives Yubin Lim ◽  
Xinyi Lin ◽  
Ai Ling Teh ◽  
Yonghui Wu ◽  
Li Chen ◽  
...  

Abstract CONTEXT Antenatal hyperglycemia is associated with increased risk of future adverse health outcomes in both mother and child. Variations in offspring’s epigenome can reflect the impact and response to in utero glycemic exposure, and may have different consequences for the child. OBJECTIVE We examined possible differences in associations of basal glucose status and glucose handling during pregnancy with both clinical covariates and offspring cord tissue DNA methylation. RESEARCH DESIGN AND METHODS This study included 830 mother-offspring dyads from the GUSTO cohort. The fetal epigenome of umbilical cord tissue was profiled using Illumina HumanMethylation450 arrays. Associations of maternal mid-pregnancy fasting (FPG) and 2h plasma glucose (2hPG) post-75g oral glucose challenge (OGTT) with both maternal clinical phenotypes and offspring epigenome at delivery were investigated separately. RESULTS Maternal age, pre-pregnancy BMI and blood pressure measures were associated with both FPG and 2hPG; while Chinese ethnicity (p=1.9×10 -4), maternal height (p=1.1×10 -4), pregnancy weight gain (p=2.2×10 -3), pre-pregnancy alcohol consumption (p=4.6×10 -4), and tobacco exposure (p=1.9×10 -3) showed significantly opposite associations between the two glucose measures. Most importantly, we observed a dichotomy in the effects of these glycemic indices on the offspring epigenome. Offspring born to mothers with elevated 2hPG showed global hypomethylation. CpGs most associated with the two glucose measures also reflected differences in gene ontologies and had different associations with offspring birthweight. CONCLUSIONS Our findings suggest that two traditionally used glycemic indices for diagnosing gestational diabetes may reflect distinctive pathophysiologies in pregnancy, and have differential impacts on the offspring’s DNA methylome.

Nutrients ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 2711
Author(s):  
Fiona S. Atkinson ◽  
Jouhrah Hussain Khan ◽  
Jennie C. Brand-Miller ◽  
Joerg Eberhard

Sugary carbohydrate foods have long been associated with increased risk of dental caries formation, but the dental health impact of starchy carbohydrates, particularly those with a high glycemic index (GI), has not been well examined. Aim: To investigate the effect of different starchy foods varying in their GI, on acute changes in dental plaque pH. Methods: In a series of sub-studies in healthy adults, common starchy carbohydrate foods, including white bread, instant mashed potatoes, canned chickpeas, pasta, breakfast cereals, white rice, and an oral glucose solution were consumed in fixed 25 g available carbohydrate portions. The change in dental plaque pH was assessed postprandially over 1 h and capillary plasma glucose was measured at regular intervals over 2 h. Results: Higher GI starchy foods produced greater acute plaque pH decreases and larger overall postprandial glucose responses compared to lower GI starchy foods (white bread compared with canned chickpeas: −1.5 vs. −0.7 pH units, p = 0.001, and 99 ± 8 mmol/L min vs. 47 ± 7 mmol/L min, p = 0.026). Controlling for other food factors (food form and nutritional composition), lower GI versions of matched food pairs produced smaller plaque pH excursions compared to higher GI versions of the same food. Using linear regression analysis, the GI value of starchy carbohydrate foods explained 60% of the variation in maximum plaque pH nadir and 64% of the variation in overall acute dental plaque pH excursion (p < 0.01). Conclusion: The findings imply that starchy foods, in particular those with a higher GI, may play a role in increasing the risk of dental caries.


Author(s):  
Cécile Bétry ◽  
Aline V. Nixon ◽  
Paul L. Greenhaff ◽  
Elizabeth J. Simpson

Abstract Introduction Skeletal muscle is a major site for whole-body glucose disposal, and determination of skeletal muscle glucose uptake is an important metabolic measurement, particularly in research focussed on interventions that impact muscle insulin sensitivity. Calculating arterial-venous difference in blood glucose can be used as an indirect measure for assessing glucose uptake. However, the possibility of multiple tissues contributing to the composition of venous blood, and the differential in glucose uptake kinetics between tissue types, suggests that sampling from different vein sites could influence the estimation of glucose uptake. This study aimed to determine the impact of venous cannula position on calculated forearm glucose uptake following an oral glucose challenge in resting and post-exercise states. Materials and Methods In 9 young, lean, males, the impact of sampling blood from two antecubital vein positions; the perforating vein (‘perforating’ visit) and, at the bifurcation of superficial and perforating veins (‘bifurcation’ visit), was assessed. Brachial artery blood flow and arterialised-venous and venous blood glucose concentrations were measured in 3 physiological states; resting-fasted, resting-fed, and fed following intermittent forearm muscle contraction (fed-exercise). Results Following glucose ingestion, forearm glucose uptake area under the curve was greater for the ‘perforating’ than for the ‘bifurcation’ visit in the resting-fed (5.92±1.56 vs. 3.69±1.35 mmol/60 min, P<0.01) and fed-exercise (17.38±7.73 vs. 11.40±7.31 mmol/75 min, P<0.05) states. Discussion Antecubital vein cannula position impacts calculated postprandial forearm glucose uptake. These findings have implications for longitudinal intervention studies where serial determination of forearm glucose uptake is required.


2022 ◽  
Vol 22 (1) ◽  
Author(s):  
Chadakarn Phaloprakarn ◽  
Siriwan Tangjitgamol

Abstract Background Blood glucose levels during pregnancy may reflect the severity of insulin secretory defects and/or insulin resistance during gestational diabetes mellitus (GDM) pregnancy. We hypothesized that suboptimal glycemic control in women with GDM could increase the risk of postpartum type 2 diabetes mellitus (T2DM) or prediabetes. Our objective was to evaluate the impact of plasma glucose levels throughout GDM pregnancy on the risk of postpartum T2DM or prediabetes. Methods The medical records of 706 women with GDM who underwent a postpartum 75-g, 2-hour oral glucose tolerance test at our institution between January 2011 and December 2018 were reviewed. These women were classified into 2 groups according to glycemic control during pregnancy: ≤ 1 occasion of either fasting glucose ≥ 95 mg/dL or 2-hour postprandial glucose ≥ 120 mg/dL was defined as optimal glycemic control or else was classified as suboptimal glycemic control. Rates of postpartum T2DM and prediabetes were compared between women with optimal (n = 505) and suboptimal (n = 201) glycemic control. Results The rates of postpartum T2DM and prediabetes were significantly higher in the suboptimal glycemic control group than in the optimal glycemic control group: 22.4% vs. 3.0%, P < 0.001 for T2DM and 45.3% vs. 23.5%, P < 0.001 for prediabetes. In a multivariate analysis, suboptimal glucose control during pregnancy was an independent risk factor for developing either postpartum T2DM or prediabetes. The adjusted odds ratios were 8.4 (95% confidence interval, 3.5–20.3) for T2DM and 3.9 (95% confidence interval, 2.5–6.1) for prediabetes. Conclusion Our findings suggest that blood glucose levels during GDM pregnancy have an impact on the risk of postpartum T2DM and prediabetes.


Author(s):  
Jason S. Au ◽  
Kayleigh M Beaudry ◽  
Kristian Pancevski ◽  
Richard L. Hughson ◽  
Michaela C. Devries

Exercise elicits direct benefits to insulin sensitivity but may also indirectly improve glucose uptake by hemodynamic conditioning of the vasculature. The purpose of this study was to examine the modifying effect of three different types of exercise on the vascular response to an oral glucose challenge. Twenty healthy adults (9 women, 11 men; 23±3 years old) completed a standard oral glucose tolerance test (OGTT) at rest, as well as 1.5 hours after moderate continuous cycling exercise (30 min; 65% V̇O2peak), high intensity interval cycling exercise (10x1 min at 90% heart rate peak), and lower-load higher-repetition resistance exercise (25-35 repetitions/set, 3 sets). Brachial and superficial femoral artery blood flow, conductance, and oscillatory shear index were measured throughout the OGTT. Regardless of rested state or exercise preconditioning, the OGTT induced reductions in brachial artery blood flow and conductance (p<0.001), and transient increases in brachial and superficial femoral artery oscillatory shear index and retrograde blood flow (p<0.01). Continuous cycling and resistance exercise were followed with a small degree of protection against prolonged periods of oscillatory flow. Our findings imply transient peripheral vasoconstriction and decreased limb blood flow during a standard OGTT, for which prior exercise was unable to prevent in healthy adults. NOVELTY BULLETS • We investigated the impact of continuous, interval, and resistance exercise on the hemodynamic response to an oral glucose tolerance test (OGTT). • Our findings suggest decreased upper-limb blood flow during an OGTT is not prevented by prior exercise in healthy adults.


2004 ◽  
Vol 107 (2) ◽  
pp. 191-196 ◽  
Author(s):  
Aris SIAFARIKAS ◽  
Katie WATTS ◽  
Petra BEYE ◽  
Timothy W. JONES ◽  
Elizabeth A. DAVIS ◽  
...  

The aim of the present study was to investigate the impact of an oral glucose load on circulating insulin and glucose levels and arterial function in healthy non-diabetic subjects. Thirty-nine non-obese, healthy subjects (24 female, 15 male), aged 21.0±1.8 years of age, were randomly assigned to undergo either an OGTT (oral glucose tolerance test; 75 g of glucose) or administration of a placebo. Analyses of lipids, liver function and HbA1c (glycated haemoglobin) at baseline revealed results which were within the standard reference range. Insulin and glucose levels as well as vascular function [FMD (flow-mediated dilation)] were measured at 0, 60 and 120 min. Compared with baseline, the control subjects did not exhibit any significant changes in glucose or insulin levels, whereas, in the OGTT group, blood glucose levels at both 60 (5.4±1.7 mmol/l) and 120 (5.0±1.1 mmol/l) min increased significantly relative to baseline (4.1±0.4 mmol/l; both P<0.001) and, similarly, insulin levels were higher at both 60 (30.1±21.3 m-units/l) and 120 (34.9±23.6 m-units/l) min compared with baseline (4.7±4.3 m-units/l; both P<0.001). Although blood glucose and insulin levels changed, FMD did not significantly differ between time-points or between groups. In summary, despite significantly elevated glucose and insulin concentrations in these subjects, we observed no change in vascular function, suggesting that acute elevations of glucose and insulin within the clinically normal range are not associated with impaired vascular function in vivo.


2019 ◽  
Vol 9 (2) ◽  
pp. 1545-1549
Author(s):  
Neha Homagai ◽  
Nirajan Mainali ◽  
Sikha Rijal

Background: Gestational diabetes mellitus is defined as any degree of glucose intolerance which is first recognized during pregnancy and is associated with a number of adverse perinatal outcomes, such as neonatal hypoglycemia, macrosomia with an increased risk of shoulder dystocia and the need for neonatal intensive care. Maternal complications include pre-eclampsia and an increased risk of caesarean delivery. The objective of this study was to compare maternal and perinatal outcomes in pregnant women with positive and negative oral glucose tolerance test following positive glucose challenge test. Materials and Methods: This is a prospective observational hospital based study of 120 patients admitted in Nobel Medical College Teaching Hospital, Biratnagar with glucose challenge test positive pregnancy for delivery. Oral glucose tolerance test was performed in all the glucose challenge test positive pregnant and compared with various maternal parameters and newborn’s conditions. Results: Among 120 patients included in the study, 28 (30.4%) cases were oral glucose tolerance test. Pregnancy induced hypertension was present in 12 cases. Hyperbilirubinemia was present in 42, hypoglycemia in 32, respiratory distress in 44, birth asphyxia in 15 and macrosomia in 6 cases. Conclusions: Pregnancy induced hypertension and hyperbilirubinemia were found to be significantly higher in OGTT positive cases so early detection of GDM screening via is advisable


2014 ◽  
Vol 33 (3) ◽  
pp. 237-244
Author(s):  
Şerif Ercan ◽  
Nihal Yücel ◽  
Asuman Orçun

Abstract Background: The subjects with impaired glucose tolerance have an increased risk for future type 2 diabetes (T2DM); however, a significant number of individuals who develop T2DM have normal glucose tolerance (NGT) at baseline. The study aims to compare glycated hemoglobin (HbA1C) and homeostasis model assessment (HOMA-IR) levels to 30, 60 and 90-min glucose levels in subjects with NGT. Methods: A 75-g oral glucose tolerance test (OGTT) at 0, 30, 60, 90 and 120-min was performed in 1118 subjects without known T2DM. Blood samples were also drawn for fasting insulin and HbA1C levels. Results: Forty percent of the subjects with NGT had increased post-challenge values above the determined optimal glucose levels (10.2, 10.3 and 8.9 mmol/L at 30, 60 and 90-min, respectively). Compared to the subjects with NGT whose glucose levels were below the determined optimal values at 30, 60 and 90-min, we found significantly elevated HbA1C and HOMA-IR levels in the subjects with NGT whose glucose levels were above the determined optimal values (p<0.001). Conclusions: We conclude that the subjects with NGT have different HbA1C and HOMA-IR levels considering glucose levels measured earlier than at 2-h during OGTT. Further well-designed prospective studies are needed to define the significance of 30-min, 60-min and 90-min glucose levels in the prediction of disease in subjects with T2DM.


2009 ◽  
Vol 160 (4) ◽  
pp. 579-584 ◽  
Author(s):  
Thomas Reinehr ◽  
Michaela Kleber ◽  
Andre Michael Toschke

ObjectiveSmall for gestational age (SGA) children are at risk of both later obesity and metabolic syndrome (MetS). However, it is unknown whether obesity or SGA status leads to MetS in these subjects. We hypothesized that overweight children with former SGA status had more present components of the MetS than overweight children with former appropriate for gestational age (AGA) status.MethodsWe analyzed 803 overweight children (4% SGA, mean age 11±0.1 years, body mass index (BMI) 27.3±0.2, SDS-BMI 2.32±0.02) concerning blood pressure, lipids, glucose, and insulin. Oral glucose tolerance tests (oGTT) were performed in all 35 former SGA children and 147 randomly chosen former non-SGA children.ResultsAfter adjustment for age, sex, pubertal stage, and BMI-SDS, former SGA status was significantly related to blood pressure, triglyceride, insulin, and 2 h glucose levels in oGTT. The MetS prevalence was more than doubled in overweight former SGA subjects (40% MetS) compared with overweight former AGA subjects (17% MetS). The corresponding adjusted odds ratio was 4.08 (95% confidence interval 1.48 to 11.22) for SGA compared with AGA children.ConclusionsOverweight former SGA children had an increased risk for the components of the MetS compared with overweight former AGA children. Therefore, SGA status seems to be a risk factor for the MetS independently of weight status. Particularly overweight children with former SGA status should be screened for the MetS.


Genes ◽  
2021 ◽  
Vol 12 (12) ◽  
pp. 1991
Author(s):  
Bachuki Shashikadze ◽  
Florian Flenkenthaler ◽  
Jan B. Stöckl ◽  
Libera Valla ◽  
Simone Renner ◽  
...  

Worldwide, gestational diabetes affects 2–25% of pregnancies. Due to related disturbances of the maternal metabolism during the periconceptional period and pregnancy, children bear an increased risk for future diseases. It is well known that an aberrant intrauterine environment caused by elevated maternal glucose levels is related to elevated risks for increased birth weights and metabolic disorders in later life, such as obesity or type 2 diabetes. The complexity of disturbances induced by maternal diabetes, with multiple underlying mechanisms, makes early diagnosis or prevention a challenging task. Omics technologies allowing holistic quantification of several classes of molecules from biological fluids, cells, or tissues are powerful tools to systematically investigate the effects of maternal diabetes on the offspring in an unbiased manner. Differentially abundant molecules or distinct molecular profiles may serve as diagnostic biomarkers, which may also support the development of preventive and therapeutic strategies. In this review, we summarize key findings from state-of-the-art Omics studies addressing the impact of maternal diabetes on offspring health.


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