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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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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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Myoinositol plus α-lactalbumin supplementation, insulin resistance and birth outcomes in women with gestational diabetes mellitus: a randomized, controlled study.
D'Anna, R, Corrado, F, Loddo, S, Gullo, G, Giunta, L, Di Benedetto, A
Scientific reports. 2021;(1):8866
Abstract
To verify whether myo-inositol plus α-lactalbumin may reduce insulin resistance and excessive fetal growth in women with gestational diabetes mellitus. In a 12-month period, 120 women with a diagnosis of gestational diabetes mellitus were consecutively enrolled with an allocation of 1:1 in each group and randomly treated with myo-inositol plus α-lactalbumin plus folic acid (treated group) or folic acid (control group) for 2 months. Primary outcome was the variation of insulin resistance through the study evaluated by HOMA-IR. Secondary outcome was the evaluation, through the study, of fetal growth by ultrasound measurements of abdominal circumference centiles and estimated fat thickness. Some clinical outcomes were also considered. After 2 months, in the treated group, a significant reduction in insulin resistance (HOMA values 3.1 ± 1.4 vs 6.1 ± 3.4, p = 0.0002) and fetal growth was shown (Abdominal circumference centiles 54.9 ± 23.5 vs 67.5 ± 22.6, P = 0.006). Among clinical outcomes, a significant decrease in the rate of women who needed insulin (6.7% vs 20.3%, p = 0.03) and of pre-term birth (0 vs 15.2%, p = 0.007) was evidenced. A combination of myo-inositol and α-lactalbumin may reduce insulin resistance and excessive fetal growth.Clinical trial registration: ClinicalTrials.gov, http://www.clinicaltrials.gov , NCT03763669, first posted date 04/12/2018; last posted date December 06/12/2018.
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Exercise during pregnancy: how much active are pregnant women at risk of gestational diabetes despite few contraindications?
Bianchi, C, de Gennaro, G, Romano, M, Baronti, W, Aragona, M, Battini, L, Bottone, P, Del Prato, S, Bertolotto, A
Gynecological endocrinology : the official journal of the International Society of Gynecological Endocrinology. 2021;(2):101-104
Abstract
INTRODUCTION Diet and physical activity are cornerstones in prevention and treatment of Gestational Diabetes (GDM) though some caution may be required under specific circumstances. The aims of this study were to evaluate activity habits during pregnancy and contraindications to physical activity in women at risk for GDM. METHODS 536 pregnant women (age 35 ± 5 years; gestation week 25 ± 4; pre-pregnancy BMI 24.6 ± 12.9 kg/m2), selective screened for GDM, filled out a standardized questionnaire recording physical activity during pregnancy. RESULTS Of 536 women, 73.4% reported regular exercise before pregnancy and 95.5% of them continued during pregnancy. 8.2% had absolute contraindications to exercise, such as placenta praevia /vaginal bleeding and incompetent cervix/cerclage. Physical activity during the last month was reported by 66.2% of women; frequency was 1-2 times/week (44%); intensity was light (83%) and duration on average (44%) 20-40 min/day. 48% of women spent most of their time in sedentary behaviors (sitting). Among women with GDM, physical activity was associated with better metabolic profile and lower needed of insulin therapy. CONCLUSION Women at risk for GDM spent most of their time in sedentary behaviors, despite a low prevalence of contraindications to exercise. Therefore, our data call for the need of motivational counseling aimed to implement physical activity during 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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The effect of intermittent energy restriction on weight loss and diabetes risk markers in women with a history of gestational diabetes: a 12-month randomized control trial.
Gray, KL, Clifton, PM, Keogh, JB
The American journal of clinical nutrition. 2021;(2):794-803
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BACKGROUND Weight loss after gestational diabetes (GDM) can prevent or delay the onset of type 2 diabetes. Intermittent energy restriction (IER) may offer an alternative to continuous energy restriction (CER) for weight loss. OBJECTIVES We compared the effects of IER (2 days per week) to daily CER over 12 mo on weight loss and diabetes risk markers in overweight women with previous GDM. METHODS Overweight females (n = 121) ≥18 y were randomized 1:1 to either IER [2-d 500 kcal (2100 kJ); n = 61] or CER [1500 kcal (6000 kJ); n = 60] in this 12-mo noninferiority trial. RESULTS The trial was completed by 62 participants with a median age of 39.6 y [Quartile (Q) 1 to Quartile 3, 34.9 to 43.9 y] with a median BMI of 32.6 kg/m2 (Q1 to Q3, 28.5 to 37.9 kg/m2) at a median of 2.9 y after GDM (Q1 to Q3, 2.1 to 6.4 y; 49% attrition; IER n = 29; CER n = 30; P = 0.8). The mean ± SD weight loss was significant over time (P < 0.001) but not by diet group (IER -4.8 ± 5.0 kg; CER -3.2 ± 5.0; P = 0.2). The mean between-group difference was -1.6 kg (95% CI: -4.2 to 1.0 kg; P = 0.2). There were no significant between-group differences in change in HbA1c, fasting plasma glucose, fasting serum insulin, HOMA-IR or 2-h oral glucose tolerance at 12 mo (p>0.05). The trial was registered at https://www.anzctr.org.au/ (ACTRN12617001476325). CONCLUSIONS IER produces comparable weight loss to CER over 12 mo in overweight women with previous GDM. The high dropout rate in this study is a limitation in the interpretation of these results. Larger studies are needed to confirm noninferiority of IER compared to CER.
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Effects of lifestyle intervention during pregnancy on postpartum diabetes among Chinese women with gestational diabetes.
Li, N, Liu, J, Zhang, C, Liu, G, Leng, J, Wang, L, Li, W, Yu, Z, Hu, G, Chan, JCN, et al
Diabetologia. 2021;(1):255-258
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The changes of Lp-PLA2 in patients with gestational diabetes and its clinical significance.
Wang, GH, Jin, J, Liu, YQ, Yang, FY, Shi, D, Zhang, Y, Zhao, YM, Wang, Y
Medicine. 2021;(30):e26786
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Gestational diabetes mellitus (GDM) is one of the most common complications of pregnancy and associated with adverse pregnancy outcomes. The aim of this study was to investigate the changes of lipoprotein-associated phospholipaseA2 (Lp-PLA2) level and its correlation with biochemical indexes in patients with GDM.This observational cross-sectional study was performed among 52 GDM and 48 healthy pregnant women. Automatic biochemical analyzer was employed to test the biochemical indexes, including fasting plasma glucose (FPG), Hemoglobin A1c (HbA1c), total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C). The lipoprotein-associated phospholipaseA2 (Lp-PLA2) level was evaluated by enzyme-linked immunosorbent assay, and homeostatic model assessment for insulin resistance (HOMA-IR) was calculated.The levels of FPG, HbA1c, HOMA-IR, TG, TC and LDL-C were significantly increased while high-density lipoprotein cholesterol (HDL-C) level was significantly decreased in the GDM group when compared with those in the control group. Lp-PLA2 level in maternal blood in the GDM group was significantly higher than that in the control group (199.125 ± 23.494 vs165.825 ± 15.576 ng/mL, P < .05) and logistic regression analysis further confirmed the association of Lp-PLA2 levels with GDM. Furthermore, Lp-PLA2 positively correlated with HOMA-IR, TC, and LDL-C.Our results confirmed the association of Lp-PLA2 with GDM. This broadens our knowledge on the pathophysiology of GDM and provides insights into the development of new targets for the prevention and treatment of GDM.
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Interaction between Metformin, Folate and Vitamin B12 and the Potential Impact on Fetal Growth and Long-Term Metabolic Health in Diabetic Pregnancies.
Owen, MD, Baker, BC, Scott, EM, Forbes, K
International journal of molecular sciences. 2021;(11)
Abstract
Metformin is the first-line treatment for many people with type 2 diabetes mellitus (T2DM) and gestational diabetes mellitus (GDM) to maintain glycaemic control. Recent evidence suggests metformin can cross the placenta during pregnancy, thereby exposing the fetus to high concentrations of metformin and potentially restricting placental and fetal growth. Offspring exposed to metformin during gestation are at increased risk of being born small for gestational age (SGA) and show signs of 'catch up' growth and obesity during childhood which increases their risk of future cardiometabolic diseases. The mechanisms by which metformin impacts on the fetal growth and long-term health of the offspring remain to be established. Metformin is associated with maternal vitamin B12 deficiency and antifolate like activity. Vitamin B12 and folate balance is vital for one carbon metabolism, which is essential for DNA methylation and purine/pyrimidine synthesis of nucleic acids. Folate:vitamin B12 imbalance induced by metformin may lead to genomic instability and aberrant gene expression, thus promoting fetal programming. Mitochondrial aerobic respiration may also be affected, thereby inhibiting placental and fetal growth, and suppressing mammalian target of rapamycin (mTOR) activity for cellular nutrient transport. Vitamin supplementation, before or during metformin treatment in pregnancy, could be a promising strategy to improve maternal vitamin B12 and folate levels and reduce the incidence of SGA births and childhood obesity. Heterogeneous diagnostic and screening criteria for GDM and the transient nature of nutrient biomarkers have led to inconsistencies in clinical study designs to investigate the effects of metformin on folate:vitamin B12 balance and child development. As rates of diabetes in pregnancy continue to escalate, more women are likely to be prescribed metformin; thus, it is of paramount importance to improve our understanding of metformin's transgenerational effects to develop prophylactic strategies for the prevention of adverse fetal outcomes.
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Maternal and neonatal outcomes after energy-restricted diet for women with gestational diabetes mellitus: A systematic review and meta-analysis of randomized controlled trials.
Feng, Y, Zhao, Z, Fu, D, Gao, W, Zhang, F
Medicine. 2021;(14):e25279
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BACKGROUND Gestational diabetes mellitus (GDM) affects 1% to 14% of pregnant women annually worldwide and is one of the most common pregnancy complications. OBJECTIVE We reviewed studies on maternal and neonatal outcomes after dietary managements for women with GDM comparing caloric-restricted (intervention group) and unrestricted diets (control group). METHODS We systematically searched online databases including Medline, Cochrane Controlled Register of Trials (CENTRAL), ScienceDirect, and Google Scholar from inception until September 2019. We performed a meta-analysis with random-effects model and reported pooled risk ratios (RRs) or pooled mean differences (MD) with 95% confidence intervals (CIs). RESULTS We analyzed data from 6 randomized controlled trials including 1300 participants, most of them with high bias risks. We found that the women in the intervention group achieved slightly better glycemic control (pooled MD, -0.72 mg/dL; 95% CI, -7.10 to 5.66 mg/dL) and overall pregnancy outcomes (except neonatal hypoglycemia) than the women in the control group. CONCLUSION An energy-restricted diet does not seem superior to the usual/standard GDM diet based on maternal or neonatal outcomes. But, clinical recommendations cannot be made as the evidence is inconclusive.