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Dichotomy in the Impact of Elevated Maternal Glucose Levels on Neonatal Epigenome.
Lim, IY, Lin, X, Teh, AL, Wu, Y, Chen, L, He, M, Chan, SY, MacIsaac, JL, Chan, JKY, Tan, KH, et al
The Journal of clinical endocrinology and metabolism. 2022;(3):e1277-e1292
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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 Growing Up in Singapore Towards Healthy Outcomes cohort. The fetal epigenome of umbilical cord tissue was profiled using Illumina HumanMethylation450 arrays. Associations of maternal mid-pregnancy fasting (fasting plasma glucose [FPG]) and 2-hour plasma glucose (2hPG) after a 75-g oral glucose challenge with both maternal clinical phenotypes and offspring epigenome at delivery were investigated separately. RESULTS Maternal age, prepregnancy body mass index, and blood pressure measures were associated with both FPG and 2hPG, whereas Chinese ethnicity (P = 1.9 × 10-4), maternal height (P = 1.1 × 10-4), pregnancy weight gain (P = 2.2 × 10-3), prepregnancy alcohol consumption (P = 4.6 × 10-4), and tobacco exposure (P = 1.9 × 10-3) showed significantly opposite associations between the 2 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 2 measures also reflected differences in gene ontologies and had different associations with offspring birthweight. CONCLUSIONS Our findings suggest that 2 traditionally used glycemic indices for diagnosing gestational diabetes may reflect distinctive pathophysiologies in pregnancy, and have differential impacts on the offspring's DNA methylome.
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Pilot Randomized Controlled Trial of Diabetes Group Prenatal Care.
Carter, EB, Barbier, K, Hill, PK, Cahill, AG, Colditz, GA, Macones, GA, Tuuli, MG, Mazzoni, SE
American journal of perinatology. 2022;(1):45-53
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Abstract
OBJECTIVE This study aimed to determine the feasibility and effectiveness of Diabetes Group Prenatal Care to increase patient engagement in diabetes self-care activities. STUDY DESIGN A pilot randomized controlled trial was conducted at two sites. Inclusion criteria were English or Spanish speaking, type 2 or gestational diabetes, 22 to 34 weeks of gestational age at first study visit, ability to attend group care at specified times, and willingness to be randomized. Exclusion criteria included type 1 diabetes, multiple gestation, major fetal anomaly, serious medical comorbidity, and serious psychiatric illness. Women were randomized to Diabetes Group Prenatal Care or individual prenatal care. The primary outcome was completion of diabetes self-care activities, including diet, exercise, blood sugar testing, and medication adherence. Secondary outcomes included antenatal care characteristics, and maternal, neonatal, and diabetes management outcomes. Analysis followed the intention-to-treat principle. RESULTS Of 159 eligible women, 84 (53%) consented to participate in the study and were randomized to group (n = 42) or individual (n = 42) prenatal care. Demographic characteristics were similar between study arms. Completion of diabetes self-care activities was similar overall, but women in group care ate the recommended amount of fruits and vegetables on more days per week (5.1 days/week ± 2.0 standard deviation [SD] in group care vs. 3.4 days ± 2.6 SD in individual care; p < 0.01) and gained less weight per week during the study period (0.2 lbs/week [interquartile range: 0-0.7] vs. 0.5 lbs/week [interquartile range: 0.2-0.9]; p = 0.03) than women in individual care. Women with gestational diabetes randomized to group care were 3.5 times more likely to have postpartum glucose tolerance testing than those in individual care (70 vs. 21%; relative risk: 3.5; 95% confidence interval: 1.4-8.8). Other maternal, neonatal, and pregnancy outcomes were similar between study arms. CONCLUSION Diabetes group care is feasible and shows promise for decreasing gestational weight gain, improving diet, and increasing postpartum diabetes testing among women with pregnancies complicated by diabetes. KEY POINTS · Women with gestational diabetes in group care were 3.5 times more likely to return for postpartum glucose tolerance testing.. · Women with gestational diabetes in group care had less gestational weight gain during the study period.. · Diabetes Group Prenatal Care is a promising intervention to improve outcomes for women with diabetes in pregnancy..
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Synbiotic supplementation for glycemic status in pregnant women: a meta-analysis of randomized clinical trials.
Luo, C, Wan, J, Rao, Z, Zhang, Y
Gynecological endocrinology : the official journal of the International Society of Gynecological Endocrinology. 2021;(2):146-151
Abstract
BACKGROUND The effect of synbiotic supplementation on glycemic status in pregnant women remained controversial and this meta-analysis aimed to explore the efficacy of synbiotic supplementation on glycemic status in pregnant women. METHODS We have searched PubMed, EMbase, Web of science, EBSCO, and Cochrane library databases and randomized controlled trials (RCTs) assessing the effect of synbiotic on glycemic status in pregnant women were included. The meta-analysis was performed using the random-effect model. RESULTS Four RCTs were included in the meta-analysis. Overall, compared with control intervention in pregnant women, synbiotic supplementation was associated with significantly reduced serum insulin (SMD = -0.69; 95%CI = -1.06 to -0.32; p = .0002) and homoeostasis model assessment of insulin resistance (HOMA-IR, SMD = -0.53; 95%CI = -0.87 to -0.18; p = .003), but had no significant effect on fasting plasma glucose (FPG, SMD = -0.16; 95%CI = -0.43 to 0.11; p = .24), quantitative insulin sensitivity check index (QUICKI, SMD = 0.54; 95%CI = -0.10 to 1.18; p = .10) or CRP (SMD = -0.29; 95%CI = -1.23 to 0.64; p = .54). CONCLUSIONS Synbiotic supplementation was beneficial to glycemic control in pregnant women.
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WeChat-assisted dietary and exercise intervention for prevention of gestational diabetes mellitus in overweight/obese pregnant women: a two-arm randomized clinical trial.
Ding, B, Gou, B, Guan, H, Wang, J, Bi, Y, Hong, Z
Archives of gynecology and obstetrics. 2021;(3):609-618
Abstract
PURPOSE This study aimed to examine the influence of a WeChat-based dietary and exercise intervention on gestational diabetes mellitus (GDM) prevention in overweight/obese pregnant women in Beijing. METHODS Overweight/obese pregnant women were recruited in the early stages of pregnancy. After screening by include and exclude standards, eligible women were randomly divided into two groups, intervention and control groups. The control group received a general advice session about pregnancy nutrition and weight management. The intervention group received three face-to-face sessions about personalized dietary and exercise intervention, with the help of WeChat as a monitoring tool to promote treatment plan adherence. At 24-28 weeks of pregnancy, GDM was diagnosed according to the International Association of Diabetes and Pregnancy Study Groups (IADPSG) criteria. Gestational weight gain (GWG), maternal and neonatal outcomes were also collected. RESULTS This study analyzed 215 participants. At the mid-trimester, 42 (37.8%) women in the control group were diagnosed with GDM (n = 111) versus 25 (24.5%) in the intervention group (n = 104; p < 0.05). The intervention group gained 11.2 ± 4.9 kg during the whole gestation period, with 4.9 ± 3.1 kg-weight increment in the first 25 weeks of pregnancy, versus 13.4 ± 5.0 kg and 6.9 ± 3.2 kg in the first 25 weeks in the control group (between groups: p < 0.001/p = 0.002). Incidence of macrosomia was not significantly lower in the intervention group than in the control group (8/7.9% vs 11/9.9%) (p > 0.05). No significant difference was found in the rate of natural labor and occurrence of perinatal complications (e.g., preterm birth, gestational hypertension, and preeclampsia) between the groups (p > 0.05). CONCLUSIONS The WeChat-assisted dietary and exercise intervention was effective in reducing the occurrence of GDM and excessive weight gain in overweight/obese pregnant women. Disseminating knowledge of pregnancy and childbirth through social media platforms like WeChat could be an important part of antenatal care.
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Dietary Blueberry and Soluble Fiber Supplementation Reduces Risk of Gestational Diabetes in Women with Obesity in a Randomized Controlled Trial.
Basu, A, Feng, D, Planinic, P, Ebersole, JL, Lyons, TJ, Alexander, JM
The Journal of nutrition. 2021;(5):1128-1138
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BACKGROUND Gestational diabetes mellitus (GDM) is a growing public health concern and maternal obesity and poor dietary intakes could be implicated. Dietary polyphenols and fiber mitigate the risk of diabetes and its complications, but little is known about their efficacy in preventing GDM. OBJECTIVES We examined the effects of whole blueberry and soluble fiber supplementation on primary outcomes of cardiometabolic profiles in women at high risk of developing GDM. METHODS Women (n = 34; mean ± SD age: 27 ± 5 y; BMI: 35.5 ± 4.0 kg/m2; previous history of GDM ∼56%; Hispanic ∼79%) were recruited in early pregnancy (<20 weeks of gestation) and randomly assigned to 1 of the following 2 groups for 18 wk: intervention (280 g whole blueberries and 12 g soluble fiber per day) and standard prenatal care (control). Both groups received nutrition education and maintained 24-h food recalls throughout the study. Data on anthropometrics, blood pressure, and blood samples for biochemical analyses were collected at baseline (<20 weeks), midpoint (24-28 weeks), and end (32-36 weeks) of gestation. Diagnosis of GDM was based on a 2-step glucose challenge test (GCT). Data were analyzed using a mixed-model ANOVA. RESULTS Maternal weight gain was significantly lower in the dietary intervention than in the control group at the end of the trial (mean ± SD: 6.8 ± 3.2 kg compared with 12.0 ± 4.1 kg, P = 0.001). C-reactive protein was also lower in the intervention than in the control group (baseline: 6.1 ± 4.0 compared with 6.8 ± 7.2 mg/L; midpoint: 6.1 ± 3.7 compared with 7.5 ± 7.3 mg/L; end: 5.5 ± 2.2 compared with 9.5 ± 6.6 mg/L, respectively, P = 0.002). Blood glucose based on GCT was lower in the intervention than in the control (100 ± 33 mg/dL compared with 131 ± 40 mg/dL, P < 0.05). Conventional lipids (total, LDL, and HDL cholesterol and triglycerides) did not differ between groups over time. No differences were noted in infant birth weight. CONCLUSIONS Whole blueberry and soluble fiber supplementation may prevent excess gestational weight gain and improve glycemic control and inflammation in women with obesity.This trial was registered at clinicaltrials.gov as NCT03467503.
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Observations of the Effects of Maternal Fasting Plasma Glucose Changes in Early Pregnancy on Fetal Growth Profiles and Birth Outcomes.
Guo, F, Liu, Y, Ding, Z, Zhang, Y, Zhang, C, Fan, J
Frontiers in endocrinology. 2021;:666194
Abstract
INTRODUCTION Although the role of maternal hyperglycemia on birth outcomes is clear, literature regarding fetal growth is scarce. We examined the possible associations between maternal fasting plasma glucose (FPG) and fetal growth. MATERIALS AND METHODS A total of 35,981 singleton-pregnant women with FPG in the first trimester were included. Fetal growth parameters were measured during pregnancy by ultrasound at mid and late pregnancy. Information on birth characteristics was retrieved from medical records. We used multivariable linear and logistic regression to determine the associations between FPG and z-scores of fetal parameters and risks of birth outcomes and to assess effect modification by maternal characteristics. RESULTS A per-unit increase in FPG levels was negatively associated with fetal parameters in mid pregnancy but positively correlated with those in late pregnancy and with birth characteristics. The effect estimates in late pregnancy were attenuated by maternal pre-pregnancy body mass index (BMI). A significant relationship between FPG and abdominal circumference (AC), an indicator of fetal adiposity, was sustained in subgroups of women with advanced age, positive family history of diabetes, and multiparity in fully adjusted models. After stratification by BMI, high FPG was associated with accelerated AC only in normal controls (0.044 SD; 95% CI: 0.010, 0.079) and overweight/obese women (0.069 SD; 95% CI: -0.002, 0.140) but not in underweight women. High FPG was an independent risk factor for large-for-gestational age in the whole group and stratified subgroups. CONCLUSIONS Increased FPG in early pregnancy is closely related to fetal growth. Maternal characteristics may modify the associations between FPG and fetal adiposity in late pregnancy.
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The relationship between plasma taurine levels in early pregnancy and later gestational diabetes mellitus risk in Chinese pregnant women.
Liu, PJ, Liu, Y, Ma, L, Liu, L, Hu, T, An, Z, Yao, AM, Xia, LY
Scientific reports. 2021;(1):7993
Abstract
Taurine is a sulfur-containing amino acid that plays an important role in glucose homeostasis. However, it remains unknown whether the plasma concentration of taurine affects the risk of later gestational diabetes mellitus (GDM) development. We recruited 398 singleton-pregnancy women and followed up them during the course of pregnancy. We measured the plasma concentrations of taurine based on blood samples collected at nine-week gestation on average and obtained the data regarding both mothers and their infants from medical records. There was a significant increment in the mean value of HOMA-β across the tertiles of plasma taurine in multiparous women rather than in primiparous women. After adjustment for confounders, an increase of plasma taurine was nominally and significantly associated with a decrease risk of GDM; moreover, women with plasma taurine concentrations in the lowest tertile and in the second tertile had a higher risk of GDM than did those with plasma taurine in the top tertile in multiparous women other than primiparous women. Plasma taurine level seems to be associated with insulin secretion in early pregnancy and be more closely associated with β-cell function and the risk of GDM development in multiparas in comparison to primiparas.
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A core outcome set for the treatment of pregnant women with pregestational diabetes: an international consensus study.
Kgosidialwa, O, Bogdanet, D, Egan, AM, O'Shea, PM, Newman, C, Griffin, TP, McDonagh, C, O'Shea, C, Carmody, L, Cooray, SD, et al
BJOG : an international journal of obstetrics and gynaecology. 2021;(11):1855-1868
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OBJECTIVE To develop a core outcome set (COS) for randomised controlled trials (RCTs) evaluating the effectiveness of interventions for the treatment of pregnant women with pregestational diabetes mellitus (PGDM). DESIGN A consensus developmental study. SETTING International. POPULATION Two hundred and five stakeholders completed the first round. METHODS The study consisted of three components. (1) A systematic review of the literature to produce a list of outcomes reported in RCTs assessing the effectiveness of interventions for the treatment of pregnant women with PGDM. (2) A three-round, online eDelphi survey to prioritise these outcomes by international stakeholders (including healthcare professionals, researchers and women with PGDM). (3) A consensus meeting where stakeholders from each group decided on the final COS. MAIN OUTCOME MEASURES All outcomes were extracted from the literature. RESULTS We extracted 131 unique outcomes from 67 records meeting the full inclusion criteria. Of the 205 stakeholders who completed the first round, 174/205 (85%) and 165/174 (95%) completed rounds 2 and 3, respectively. Participants at the subsequent consensus meeting chose 19 outcomes for inclusion into the COS: trimester-specific haemoglobin A1c, maternal weight gain during pregnancy, severe maternal hypoglycaemia, diabetic ketoacidosis, miscarriage, pregnancy-induced hypertension, pre-eclampsia, maternal death, birthweight, large for gestational age, small for gestational age, gestational age at birth, preterm birth, mode of birth, shoulder dystocia, neonatal hypoglycaemia, congenital malformations, stillbirth and neonatal death. CONCLUSIONS This COS will enable better comparison between RCTs to produce robust evidence synthesis, improve trial reporting and optimise research efficiency in studies assessing treatment of pregnant women with PGDM. TWEETABLE ABSTRACT 165 key stakeholders have developed #Treatment #CoreOutcomes in pregnant women with #diabetes existing before pregnancy.
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Dietary supplementation for gestational diabetes prevention and management: a meta-analysis of randomized controlled trials.
Chan, KY, Wong, MMH, Pang, SSH, Lo, KKH
Archives of gynecology and obstetrics. 2021;(6):1381-1391
Abstract
PURPOSE The use of supplement to prevent and ease gestational diabetes (GDM) progression has been examined in various studies, but the results were inconclusive, and studies evaluated dietary supplements separately. The present review aimed to evaluate the efficacy of various dietary supplementation on GDM risk and the surrogate markers for cardiometabolic risk of pregnant women with GDM. METHODS A comprehensive search on multiple databases were performed to identify randomized controlled trials. Random-effects model was used to pool the results in relative risk (RR) or mean difference. RESULTS Fifty-three randomized controlled studies with 9443 pregnant women were included. Vitamin D (5 studies, RR 0.64; 95% CI 0.44, 0.94) and myo-inositol (4 studies, RR 0.34, 95% CI 0.20, 0.58) supplementation significantly reduced the risk of GDM. Myo-inositol, probiotics, and vitamin D showed significant intervention effect on surrogate markers related to glycemic control, lipid profile, inflammatory, and oxidative stress. However, the majority of included studies were clustered to Iran and Italy, which might convey a generalizability bias. CONCLUSION Dietary supplementation including vitamin D and myoinositol supplementation has the potential in primary prevention and management of GDM, whereas probiotics demonstrated its ability in GDM management by improving the levels of surrogate markers for cardiometabolic risk. The potential for dietary supplement in preventing GDM or managing cardiometabolic risk of pregnant women should receive more attentions.
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Associations between parity, pregnancy loss, and breastfeeding duration and risk of maternal type 2 diabetes: An observational cohort study.
Huo, Y, Cheng, L, Wang, C, Deng, Y, Hu, R, Shi, L, Wan, Q, Chen, L, Zeng, T, Yu, X, et al
Journal of diabetes. 2021;(11):857-867
Abstract
BACKGROUND Parity, pregnancy loss, and breastfeeding duration were found to be associated with diabetes. However, the results are inconsistent. Also, no epidemiological studies have examined the association of these reproductive factors with diabetes in the same large population. We aim to investigate the associations between parity, pregnancy loss, breastfeeding duration, and the risk of maternal diabetes in middle-aged and elderly Chinese females. METHODS We included 131 174 females aged ≥40 years from the REACTION study (Risk Evaluation of Cancers in Chinese Diabetic Individuals: A Longitudinal Study). Multivariable linear regression and logistic regression were used to assess the association between parity, pregnancy loss, and breastfeeding duration and type 2 diabetes. RESULTS The number of parities and breastfeeding duration were positively related to fasting plasma glucose, 2-hour postload glucose, glycosylated hemoglobin, and homeostatic model assessment of insulin resistance. Compared with those with one birth, nulliparous women or women with 2 or ≥3 births had a significantly increased risk of diabetes. The odds ratios (OR) and 95% confidence intervals (CI) were 1.27 (1.10-1.48), 1.17 (1.12-1.22), and 1.28 (1.21-1.35), respectively. Compared with women without pregnancy loss, those who underwent 2 (OR 1.09; 95% CI, 1.04-1.14) or ≥3 pregnancy losses (OR 1.11; 95% CI, 1.04-1.18) had an increased risk of diabetes. Moreover, women with a breastfeeding duration ≥0 to 6 months (OR 0.82; 95% CI, 0.75-0.90) and ≥6 to 12 months (OR 0.94; 95% CI, 0.89-0.99) had a significantly lower risk of diabetes. CONCLUSIONS Nulliparous women or women with multiparity or more than one pregnancy loss have an increased risk of diabetes in later life, while women who breastfeed more than 0 to 12 months have a lower risk of diabetes.