Gestational Diabetes Mellitus Pregnancies Research Articles

Epigenetic aging 4–10 years after a gestational diabetes mellitus pregnancy

One study has revealed an association between GDM exposure and offspring age acceleration compared to non-GDM exposed offspring. This association has not been evaluated expansively. Our study seeks to expand this area of research to evaluate the association between exposure to a GDM pregnancy and accelerated epigenetic aging. This cohort included 137 mother-child dyads (GDM-OB = 66 mothers, 61 offspring; Normal Weight/NW = 71 mothers, 55 offspring) who gave birth 4–10 years before enrollment. Demographic characteristics and whole blood samples from mothers and offspring were collected. A MethylEPIC 850K array was performed. Epigenetic age and the residuals from age acceleration were calculated using the Horvath epigenetic clock. The mean epigenetic age of mothers in the GDM group was higher than the NW group (M = 48.4 ± 8.5; M = 43.4 ± 9.7; X2 = 15.8, P < .0001, respectively). Offspring of NW mothers had a higher epigenetic age than offspring of GDM mothers (M = 20.2 ± 7.7; M = 17.3 ± 8.4; X2 = 13.9, P = .0002, respectively). Mothers with a NW and GDM pregnancy had a strong positive correlation between chronological age and epigenetic age (r = 0.76, P = 1.8E-12; r = 0.72, P = <2.2E-16, respectively). NW and GDM offspring had moderate correlations between chronological age and epigenetic age (r = 0.43, P = .0011; r = 0.65, P = 1.3E-08, respectively). Mothers in the GDM group had a higher mean epigenetic age than mothers in the NW group. Offspring of NW Mothers had a higher average epigenetic age than offspring of GDM Mothers. Accelerated aging in pediatric populations remains an understudied area, enhancing the impact of quantification of methylation age vs. chronological age in mother-child dyads from our study.

LBODP049 Clinical And Biochemical Markers In Early Pregnancy For Prediction Of Gestational Diabetes Mellitus

Abstract Background Early identification of Gestational Diabetes Mellitus (GDM) is pivotal to reduce feto-maternal complications associated with the disease. Current risk prediction models that are based on maternal clinical and biochemical parameters lack a strong predictive value. Objective To evaluate the early trimester maternal parameters for prediction of gestational diabetes mellitus. Methods In this prospective observational study, we screened 581 consecutive healthy women with singleton pregnancy for GDM during their first antenatal visit. After informed consent, fasting blood samples were collected and stored at -800C. GDM was diagnosed as per IADPSG criteria. During prospective follow up, total 55 patients developed GDM. A total of 110 age and BMI matched controls were recruited for comparison. In all women, we measured Oral Glucose Tolerance test (OGTT) with 75 gm anhydrous glucose, fasting insulin, HbA1c, hsCRP, uric acid and Lipid Profile. HOMA-IR, HOMA-β and QUICKI were used to evaluate insulin sensitivity and β-cell function. Results Significant higher proportion of subjects in GDM cohort had presence of acanthosis nigricans and positive family history of Type 2 Diabetes Mellitus in first degree relative. The GDM cohort had significantly higher median waist circumference, 2hr plasma glucose (2hr PPG), HbA1c, fasting insulin, HOMA-IR, uric acid and serum triglyceride levels. The receiver operating characteristic (ROC) curve were as follows: HbA1c - 0.74 (95%CI: 0.661–0.819), Fasting Insulin - 0.748 (95%CI: 0.671–0.826), high sensitivity C-Reactive Protein (hsCRP) - 0.689 (95%CI: 0.605 - 0.773) and Uric acid - 0.718 (95%CI: 0.635–0.802). Multiple regression analysis revealed HbA1c (OR 5.264; p=0. 007), 2hr PPG (OR 1. 026; p=0. 035), QUIKI (OR 1. 057; p=0. 016), uric acid (OR 1. 039; p=0. 013) and neutrophil: lymphocyte ratio (OR 1.545; p=1. 008) to be independently associated with GDM outcome with combined area under the curve (AUC) of 0.850, a sensitivity of 72.7% and a specificity of 87.3%. Conclusions Fasting Insulin, HbA1c, HOMA-IR, hsCRP and Uric acid levels are significantly increased in early pregnancy in individuals who develop GDM subsequently, compared to women who did not develop GDM. Hence utilization of these parameters may identify at risk group in routine clinical care and help in improving feto-maternal outcome. Presentation: No date and time listed

RF16 | PSUN177 Predictors of Postpartum Depressive Symptoms in Women with Recent GDM

Abstract Background Patients with gestational diabetes mellitus (GDM) have an increased risk of developing type 2 diabetes mellitus (T2DM) after delivery and are encouraged to practice behaviors, such as healthy nutrition, physical activity and weight loss to attenuate future risk of T2DM. GDM has been shown to significantly increase the risk for post-partum depressive symptoms, which can impair a woman's ability to engage in and adhere to diabetes prevention efforts. To further inform the development and adapation of lifestyle interventions to prevent T2DM, we sought to identify factors associated with depressive symptoms in the early postpartum period among women with recent GDM. Methods Participants are from the baseline cohort of the Balance after Baby Intervention study, a two-year randomized clinical trial of a lifestyle intervention for women with recent history GDM conducted in Boston, MA and Denver, CO between 2016-2019. Prior to randomization, a study visit was scheduled at approximately 6 weeks post-partum. At this visit, weight and height were measured for determination of BMI. We administered the Edinburgh Postpartum Depression Scale (EPDS) and Perceived Stress Scale (PSS-10). We used an EPDS score of ≥9 as depressive symptoms and a PSS score of ≥14 as moderate to high perceived stress. We collected self-reported pre-pregnancy weight, and reviewed medical records to obtain medical history, including GDM diagnosis, mode of delivery, gestational weight gain and insulin use during pregnancy. We conducted bivariate analyses to identify predictors of postpartum depressive symptoms, then modeled the odds of post-partum depressive symptoms using multivariate logistic regression. Results Our study included 181 women (mean age, SD 32.6 ± 5.3 years, 51.4% White/14.4% Black/33.7% Latinx, mean pre-pregnancy BMI 29.8 ± 6.0 kg/m2). 19% of women scored ≥9 on EPDS and 53% of women scored ≥14 on PSS at the post-partum visit. Variables included in the bivariate analysis were age, Black/Latinx-identifying, college completion, perceived stress, primiparity, having a partner, pre-pregnancy BMI, gestational weight gain, C-section, insulin use during pregnancy, breastfeeding, 1st GDM pregnancy, exceeding IOM weight gain guidelines and income level. Of those variables, the best fit multivariate model with the lowest Akaike information criterion (AIC) included perceived stress, C-section and 1st GDM pregnancy. Using this model, the regression analysis showed that only perceived stress (4.5 OR, 95% CI [2.6-7.7], p was predictive of post-partum depressive symptoms. Conclusion Perceived stress was predictive of post-partum depressive symptoms in women with recent GDM. Addressing perceived stress in the early post-partum period may be an important target for development or adaptations of future lifestyle interventions to prevent T2DM in women with recent GDM. Presentation: Sunday, June 12, 2022 12:30 p.m. - 2:30 p.m., Sunday, June 12, 2022 1:18 p.m. - 1:23 p.m.

Effects of High-dose Folic Acid Supplementation on Maternal/Child Health Outcomes: Gestational Diabetes Mellitus in Pregnancy and Insulin Resistance in Offspring

ObjectivesThe purpose of this study was to evaluate the effects of maternal high folic acid (FA) supplementation during pregnancy on glucose intolerance in dams and insulin resistance in offspring. MethodsWistar female rats (n=18) were mated and randomly divided into 3 groups: a control group and 2 experimental groups. Three different feeding protocols were administered during pregnancy: control group, 2 mg/kg FA (recommended level FA supplementation); experimental 1 group, 5 mg/kg FA (tolerable upper intake level of FA supplementation [ULFolS]); and experimental 2 group, 40 mg/kg FA (high FA supplementation [HfolS]). All dams were fed the same FA content diet (2 mg/kg FA) during the lactation period. An oral glucose tolerance test was performed on day 16 of pregnancy. After the lactation period, body weight and food intake of 36 pups were monitored. Dams were euthanized at the end of the lactation period and half of the pups were euthanized at the end of week 7 and the others at the end of week 12. Serum FA, homocysteine, vitamin B12, insulin, glucose, interleukin-6, tumor necrosis factor-alpha, glycated hemoglobin (A1C), and adiponectin levels of mothers and pups were evaluated. The homeostatic model of insulin resistance (HOMA-IR) was used to determine insulin resistance in dams and offspring. ResultsAccording to glucose tolerance test results of dams, blood glucose values at minutes 0, 60, 90, and 120 for the HFolS group were significantly higher compared with the control group (p<0.05). The A1C level in HFolS dams was significantly higher than in the control group (p<0.05). The mean birthweight of the pups in the HFolS group was significantly higher than that of control pups (p<0.05). HOMA-IR values for control and HFolS offspring were similar at weeks 7 and 12 and higher than in ULFolS offspring (p>0.05). ConclusionsIt was determined that high doses of FA exposure during pregnancy might be effective in the development of glucose intolerance in dams and insulin resistance in offspring in this study.

Cardiac Troponin T in Neonates from Normal and Gestational Diabetes Mellitus Pregnancy.

This study is aimed at testing the hypothesis that serum analysis of high-sensitivity troponin T in neonates may serve as a diagnostic tool to predict the risk of gestational diabetes mellitus (GDM). 86 newborns were studied and stratified into two groups: healthy group; newborns with body weight ≥ 10th percentile, born in good condition (APG 8-10pts) of pregnancy not complicated by diabetes, and the GDM group; neonates born to mothers with type 1 or type 2 diabetes. Results. The study revealed minimal troponin levels in GDM, and healthy groups equal to 0.02 ng/mL and 0.028 ng/mL, respectively. The GDM group is defined by an interquartile range of hs-TnT higher than the healthy group. This study confirms previously reported upper levels of troponin in healthy children. There are possible health problems that can appear during infancy and influence the further development of a child affected by GDM.

The Relationship Between Subclinical Hypothyroidism and Gestational Diabetes Mellitus

The most common metabolic disorder during pregnancy is gestational diabetes mellitus (GDM). GDM can occur in anywhere between 1.7 and 11.6 percent of people. In hypothyroidism, the rates of glucose oxidation and glycogen synthesis are reduced, and the peripheral tissues' consumption of glucose is also delayed. Patients with subclinical and overt hypothyroidism develop insulin resistance because insulin is unable to adequately maintain the muscles' use of glucose. According to the literature, hypothyroidism is linked to 6–15 percent of GDM pregnancies. Additionally, the chance of having GDM is 4.3 times higher in pregnant women who have hypothyroidism. This study aimed to reveal the relationship between first-trimester thyroid function tests and GDM. This retrospective cohort study was conducted between May 2021 and May 2022. 100 pregnant patients diagnosed with GDM and 500 healthy controls were included in the study. Using a 75 g glucose challenge test, GDM was identified. The trimester-specific recognized normal limits were used to evaluate the TSH and fT4 readings. There was a statistically significant difference in terms of SCH between patients with and without GDM (p=0.04). TSH's performance in predicting GDM was evaluated using AUC and ROC (AUC=0.586 and p=0.006). To forecast GDM, the TSH level cut-off value was discovered to be 1.58. The AUC was found to be 0.586 (0.521-0.652). Furthermore, the selectivity is 58% and the sensitivity is 41%. There are many studies in the literature investigating thyroid functions and the development of gestational diabetes mellitus. Our study also found a correlation between the diagnosis of subclinical hypothyroidism in the first trimester and GDM. The study adds to the literature the importance of being cautious and vigilant in terms of the development of gestational diabetes mellitus based on the results of the thyroid function test in the first trimester.

Optimal gestational weight gain in women with twin pregnancies and gestational diabetes mellitus: a population-based study in the United States

There is limited evidence regarding optimal gestational weight gain in women with twin pregnancies and gestational diabetes mellitus. This study aimed to examine the association between gestational weight gain and perinatal outcomes among women with gestational diabetes mellitus and twin pregnancies and to explore the gestational weight gain targets by prepregnancy body mass index category. A national population-based cohort study of twin pregnancies with gestational diabetes mellitus was conducted between 2014 and 2020. Women with gestational diabetes mellitus aged between 18 and 45 years with live-born twins without congenital malformations between 24 and 42 weeks of gestation were included in the analysis. Two approaches were used to determine the optimal gestational weight gain targets by body mass index category: an interquartile range method to calculate targets in low-risk gestational diabetes mellitus pregnancies and a logistic model method to identify the odds ratio targets at which a composite adverse outcome decreased. Of 29,308 women with gestational diabetes mellitus and twin pregnancies, 8239 (28.1%) were normal-weight, 7626 (26.0%) were overweight, and 13,443 (45.9%) were obese. The continuous standardized gestational weight gain by 36 weeks was associated with preterm birth <36 weeks, large-for-gestational-age infants, small-for-gestational-age infants, and gestational hypertensive disorders. The interquartile range targets were 13.6 to 20.9 kg, 10.9 to 20.4 kg, and 7.7 to 17.7 kg for normal-weight, overweight, and obese women, respectively. The odds ratio targets were 14.1 to 20.0 kg, 12.1 to 16.0 kg, and 6.1 to 12.0 kg for normal-weight, overweight, and obese women, respectively. Gestational weight gain outside these targets was associated with preterm birth <36 weeks, large-for-gestational-age and small-for-gestational-age infants, and gestational hypertensive disorders, and exhibited significant population attributable fractions for preterm birth <36 weeks, large-for-gestational-age infants, and gestational hypertensive disorders across body mass index categories. Compared with the Institute of Medicine guidelines, more stringent gestational weight gain targets would be beneficial for improved perinatal outcomes in women with gestational diabetes mellitus and twin pregnancies.

New born macrosomia in gestational diabetes mellitus.

Gestational diabetes mellitus (GDM) is a metabolic complication of pregnancy. The pathogenesis of GDM is considered to involve β-cell dysfunction and insulin resistance (IR). GDM is associated with a significant risk of macrosomia in addition to a high probability of metabolic complications for the offspring. The precise mechanism underlying GDM remains unclear. The aim of the present study was to analyse the factors associated with insulin resistance and β-cell dysfunction involved in the pathophysiology of GDM complicated with macrosomia compared with GDM without macrosomia. In addition, another aim of the present study was to assess the relationship between GDM complicated with macrosomia and anthropometric, clinical and paraclinical parameters. The following group of patients were recruited as part of a case-control study: Patients with GDM without macrosomia, patients with GDM complicated with macrosomia and healthy gestational controls. Blood samples were collected at the third trimester of pregnancy and tested for adiponectin, leptin, insulin, proinsulin and C-peptide. Homeostatic model assessment-IR (HOMA-IR), steady state β-cell function (HOMA%B), insulin sensitivity (HOMA%S) and body mass index (BMI) were also calculated. All patients diagnosed with GDM showed an impairment in HOMA%B and a decrease in C-peptide maternal serum concentration. Additionally, diabetic status leading to the birth of offspring with macrosomia did not induce changes in the maternal serum levels of insulin, proinsulin, adiponectin or leptin, which was also the case in patients with GDM but not macrosomia. HOMA%B presented a stronger positive correlation with pre-pregnancy BMI and maternal weight gain, and a stronger negative correlation with adiponectin. Furthermore, HOMA%S in this group exhibited strong positive correlations with maternal serum levels of high-density lipoprotein cholesterol (HDL) and aspartate aminotransferase, and a strong negative correlation with pre-pregnancy BMI. In the same patients, HOMA-IR was also found to have a high negative correlation with HDL levels, and highly positive correlations with gestational age and triglyceride levels. In conclusion, the present study suggests that the different correlations among the factors involved in the pathogenesis of GDM may explain the evolution of GDM pregnancy to macrosomia.

THE IMPACT OF GESTATIONAL DIABETES ON THE CARDIOVASCULAR HEALTH OF THE CHILD

There is increasing evidence that fetal exposures influence lifelong cardiovascular (CV) health. Gestational diabetes mellitus (GDM) represents one such exposure that influences both the short- and long-term health of offspring, but the extent to which changes in CV structure and function are present in exposed children has not been fully investigated. In the present study, we explored the CV health of children (CGDM) of mothers who developed GDM compared to children of mothers without GDM in pregnancy.

Cut-off points of 75-gram oral glucose tolerance test as a diagnostic test for gestational diabetes mellitus in pregnant Filipino population

Background: Cut-off points determine the threshold of health status in a patient. For instance, in pregnancy, cut off points of oral glucose tolerance test (OGTT) distinguishes gestational diabetes mellitus (GDM) pregnancy from healthy condition. Currently, OGTT cut-off points used in the Philippines was standardized using a different reference population, which may impact disease diagnosis. This study aims to establish the cut-off points of 75-grams (g) OGTT for the diagnosis of GDM among Filipino pregnant women.

Subklinik Hipotiroidizm ile Gestasyonel Diabetes Mellitus Arasındaki İlişki

Aim: The most common metabolic disorder during pregnancy is gestational diabetes mellitus (GDM). GDM can occur in anywhere between 1.7 and 11.6 percent of people. In hypothyroidism, the rates of glucose oxidation and glycogen synthesis are reduced, and the peripheral tissues' consumption of glucose is also delayed. Patients with subclinical and overt hypothyroidism develop insulin resistance because insulin is unable to adequately maintain the muscles' use of glucose. According to the literature, hypothyroidism is linked to 6–15 percent of GDM pregnancies. Additionally, the chance of having GDM is 4.3 times higher in pregnant women who have hypothyroidism. This study aimed to reveal the relationship between first-trimester thyroid function tests and GDM. &#x0D; Material and Method: This retrospective cohort study was conducted between May 2021 and May 2022. 100 pregnant patients diagnosed with GDM and 500 healthy controls were included in the study. Using a 75 g glucose challenge test, GDM was identified. The trimester-specific recognized normal limits were used to evaluate the TSH and fT4 readings.&#x0D; Results: There was a statistically significant difference in terms of SCH between patients with and without GDM (p=0.04). TSH's performance in predicting GDM was evaluated using AUC and ROC (AUC=0.586 and p=0.006). To forecast GDM, the TSH level cut-off value was discovered to be 1.58. The AUC was found to be 0.586 (0.521-0.652). Furthermore, the selectivity is 58% and the sensitivity is 41%&#x0D; Conclusion: There are many studies in the literature investigating thyroid functions and the development of gestational diabetes mellitus. Our study also found a correlation between the diagnosis of subclinical hypothyroidism in the first trimester and GDM. The study adds to the literature the importance of being cautious and vigilant in terms of the development of gestational diabetes mellitus based on the results of the thyroid function test in the first trimester.

Diabetes in Women After Gestational Diabetes: A Missed Opportunity for Prevention

Women with a history of gestational diabetes mellitus (GDM) are at high risk of developing type 2 diabetes (T2D). On average, one third of women develop T2D within 15 years of their GDM pregnancy.1 In a recent analysis, the rate of GDM in U.S. pregnancies was more than 6% and was noted to be increasing by close to 4% per year from 2011 to 2019.2 The coronavirus disease 2019 (COVID-19) pandemic has further exacerbated concerns about the rising global prevalence of GDM because more women appear to be developing this condition because of factors such as increased sedentary behavior, weight gain, and stress during the pandemic.

The relationship between poor glycaemic control at different time points of gestational diabetes mellitus and pregnancy outcomes

We aimed to identify the complications of gestational diabetes mellitus (GDM) associated with poor control of fasting plasma glucose (FPG) and postload plasma glucose (PPG) on the 75-g oral glucose tolerance test (OGTT). This retrospective study included 997 singleton pregnancy GDM patients who were assigned to poor or good glycaemic control groups. Multivariate analysis indicated that poor FPG control and poor PPG control were both independent predictors of hypertensive disorder complicating pregnancy (HDCP) (odd ratio (OR) of 2.551 (95% CI [1.146–5.682], p = .022) and OR of 2.084 (95% [1.115–3.894], p = .021) compared with good glycaemic control groups, respectively). Poor PPG control promoted the rate of caesarean delivery (1.534 (95% CI [1.063–2.214]), p = .022), whereas good PPG control increased the risk of premature rupture of membranes (PROM) (0.373 (95% CI [0.228–0.611]), p < .001). Conclusively, poor control FPG and PPG dissimilarly affect pregnancy complications in GDM; these findings may help clinicians in the effective implementation of measures to prevent pregnancy complications in GDM. IMPACT STATEMENT What is already known on this subject? Previous studies displayed that GDM patients with 2-h PPG elevated at 24–28 week of gestation had a 2.254-fold increased risk of postpartum dysglycaemia. Abnormal plasma glucose in GDM mother increased the probability of childhood obesity in the offspring. With the implementation of China’s second-child policy, the incidence of GDM is rising. What do the results of this study add? Our results indicated that the older patients with GDM, the greater the risk of abnormal plasma glucose control. In addition, maternal age and prenatal BMI were notably correlated with poor plasma glucose control of FPG and PPG, respectively. We also found that both poor FPG and PPG control notably increased the incidence of HDCP in pregnant women. The incidence of PROM was higher in the good PPG control group compared with the poor PPG control group. What are the implications of these findings for clinical practice and/or further research? This study displayed that the effects of poor FPG and PPG control on pregnancy complications and newborn outcomes were heterogeneous, which might be related to the specificity of plasma glucose metabolism at different time points. Good glycaemic control, especially PPG control, was of great significance for improving pregnancy complications and perinatal conditions.

Cardiovascular Disease-Associated MicroRNAs as Novel Biomarkers of First-Trimester Screening for Gestational Diabetes Mellitus in the Absence of Other Pregnancy-Related Complications

We assessed the diagnostic potential of cardiovascular disease-associated microRNAs for the early prediction of gestational diabetes mellitus (GDM) in singleton pregnancies of Caucasian descent in the absence of other pregnancy-related complications. Whole peripheral venous blood samples were collected within 10 to 13 weeks of gestation. This retrospective study involved all pregnancies diagnosed with only GDM (n = 121) and 80 normal term pregnancies selected with regard to equality of sample storage time. Gene expression of 29 microRNAs was assessed using real-time RT-PCR. Upregulation of 11 microRNAs (miR-1-3p, miR-20a-5p, miR-20b-5p, miR-23a-3p, miR-100-5p, miR-125b-5p, miR-126-3p, miR-181a-5p, miR-195-5p, miR-499a-5p, and miR-574-3p) was observed in pregnancies destinated to develop GDM. Combined screening of all 11 dysregulated microRNAs showed the highest accuracy for the early identification of pregnancies destinated to develop GDM. This screening identified 47.93% of GDM pregnancies at a 10.0% false positive rate (FPR). The predictive model for GDM based on aberrant microRNA expression profile was further improved via the implementation of clinical characteristics (maternal age and BMI at early stages of gestation and an infertility treatment by assisted reproductive technology). Following this, 69.17% of GDM pregnancies were identified at a 10.0% FPR. The effective prediction model specifically for severe GDM requiring administration of therapy involved using a combination of these three clinical characteristics and three microRNA biomarkers (miR-20a-5p, miR-20b-5p, and miR-195-5p). This model identified 78.95% of cases at a 10.0% FPR. The effective prediction model for GDM managed by diet only required the involvement of these three clinical characteristics and eight microRNA biomarkers (miR-1-3p, miR-20a-5p, miR-20b-5p, miR-100-5p, miR-125b-5p, miR-195-5p, miR-499a-5p, and miR-574-3p). With this, the model identified 50.50% of GDM pregnancies managed by diet only at a 10.0% FPR. When other clinical variables such as history of miscarriage, the presence of trombophilic gene mutations, positive first-trimester screening for preeclampsia and/or fetal growth restriction by the Fetal Medicine Foundation algorithm, and family history of diabetes mellitus in first-degree relatives were included in the GDM prediction model, the predictive power was further increased at a 10.0% FPR (72.50% GDM in total, 89.47% GDM requiring therapy, and 56.44% GDM managed by diet only). Cardiovascular disease-associated microRNAs represent promising early biomarkers to be implemented into routine first-trimester screening programs with a very good predictive potential for GDM.

Composition of Maternal Circulating Short-Chain Fatty Acids in Gestational Diabetes Mellitus and Their Associations with Placental Metabolism.

Short-chain fatty acids (SCFAs), which are produced by gut microbiota from dietary fiber, have become candidates for gestational diabetes mellitus (GDM) treatment. However, the associations of circulating SCFAs with maternal–neonatal clinical parameters in GDM and further influences on placental immune–metabolic responses are unclear. Acetate, propionate, and butyrate were decreased in GDM during the second and third trimesters, especially in those with abnormal glucose tolerance at three “oral glucose tolerance test” time points. Butyrate was closely associated with acetate and propionate in correlation and dynamic trajectory analysis. Moreover, butyrate was negatively correlated with white blood cell counts, neutrophil counts, prepregnancy BMI, gestational weight gain per week before GDM diagnosis, and ponderal index but positively correlated with total cholesterol and low-density lipoprotein levels in all pregnancies. On the premise of reduced SCFA contents in GDM, the placental G-protein-coupled receptors 41 and 43 (GPR41/43) were decreased, and histone deacetylases (HDACs) were increased, accompanied by enhanced inflammatory responses. The metabolic status was disturbed, as evidenced by activated glycolysis in GDM. Maternal circulating acetate, propionate, and butyrate levels were associated with demographic factors in normal and GDM women. They influenced placental function and fetal development at birth through GPRs or HDACs, providing more evidence of their therapeutic capacity for GDM pregnancies.

Role of Excessive Weight Gain During Gestation in the Risk of ADHD in Offspring of Women With Gestational Diabetes.

Although attention-deficit/hyperactivity disorder (ADHD) has been associated with gestational diabetes mellitus (GDM) and maternal obesity, excessive weight gain (EWG) during pregnancy has scarcely been evaluated. This study aimed to assess the joint effect of maternal weight and EWG on the risk of ADHD in offspring of GDM pregnancies. In this cohort study of singleton births >22 weeks of gestation of women with GDM between 1991 and 2008, gestational weight gain above the National Academy of Medicine (NAM) recommendations was classified into EWG. Cox-regression models estimated the effect of maternal pregestational weight and EWG on the risk of ADHD (identified from medical records), adjusted for pregnancy outcomes and GDM-related variables. Of 1036 children who were included, with a median follow-up of 17.7 years, 135 (13%) were diagnosed with ADHD. ADHD rates according to pregestational maternal weight were 1/14 (7.1%) for underweight, 62/546 (11.4%) for normal weight, 40/281 (14.2%) for overweight, and 32/195 (16.4%) for obesity. Only maternal obesity was independently associated with ADHD (HRadjusted 1.66 [95% CI, 1.07-2.60]), but not maternal overweight or EWG. On evaluating the joint contribution of maternal weight and EWG, maternal obesity with EWG was associated with the highest risk of ADHD (vs normal weight without EWG; HRadjusted 2.13 [95% CI, 1.14-4.01]). Pregestational obesity without EWG was no longer associated (HRadjusted 1.36 [95% CI, 0.78-2.36]). Among GDM pregnancies, pregestational obesity was associated with a higher risk of ADHD in offspring. Nonetheless, when gestational weight gain was taken into account, only the joint association of obesity and EWG remained significant.

Effect of magnesium supplementation on pregnancy outcome in gestational diabetes mellitus patients: A meta-analysis of randomized controlled trials.

Conflicting evidence exists regarding the effectiveness of magnesium supplementation during pregnancy in gestational diabetes mellitus (GDM) patients. This meta‐analysis examines the effect of magnesium on glycemic indices and metabolic status in GDM. We searched databases for randomized controlled trials (RCTs) conducted, and after applying inclusion and exclusion criteria, a total of four RCTs were considered eligible for the analysis. Outcome parameters included markers for glycemic control and metabolic status. A total of four RCTs with 198 participants (control = 99; magnesium supplemented = 99) were selected for the analysis. Magnesium supplementation resulted in a significant reduction in markers of glycemic control—fasting plasma glucose (standard mean difference (μ^) = −0.83; 95% CI: [−1.13, –0.54]; p‐value <.0001), and insulin levels (μ^ = −0.95; 95% CI: [−1.38, −0.52]; p‐value <.0001). Also, Mg intake resulted in altered oxidative stress markers TAC (μ^ = 1.09; 95% CI: [0.10, 2.07]; p‐value = .03) of the pregnant women. No significant effect on GSH and CRP levels was observed. This study provides evidence of the positive effects of magnesium intervention on insulin sensitivity and oxidative stress in GDM patients.

Predictive Gestational Diabetes Biomarkers With Sustained Alterations Throughout Pregnancy.

Gestational diabetes mellitus (GDM) results in an increased risk of pre- and postpartum health complications for both mother and child. Metabolomics analysis can potentially identify predictive biomarkers and provide insight into metabolic alterations associated with GDM pathogenesis and progression, but few metabolomics studies investigate alterations observed across the first and third trimester. We hypothesize that metabolites altered in first-trimester GDM that remain altered in late pregnancy may best inform interventions. Metabolomic studies comparing plasma and serum metabolite alterations in GDM vs non-GDM pregnancies were retrieved by searching PubMed, Medline, and CINAHL Plus databases. The present scoping review summarizes the metabolites found to be consistently altered throughout the course of GDM and proposes mechanisms that explain how these metabolic perturbations relate to GDM development and progression. Metabolites involved in fatty acid metabolism, reductive carboxylation, branched-chain amino acid metabolism, cell membrane lipid metabolism, purine degradation, and the gut microbiome were found to be altered throughout GDM pregnancies, with many of these pathways showing mechanistic links to insulin resistance, inflammation, and impaired cell signaling. Future studies are required to investigate if normalization of these perturbed pathways can be the targets of interventions.

A Predictive Model for Large-for-Gestational-Age Infants among Korean Women with Gestational Diabetes Mellitus Using Maternal Characteristics and Fetal Biometric Parameters.

Background: With increasing incidence of gestational diabetes mellitus (GDM), newborn infants with perinatal morbidity, including large-for-gestational-age (LGA) or macrosomia, are also increasing. The purpose of this study was to develop a prediction model for LGA infants with GDM mothers. Methods: This was a retrospective case-control study of 660 women with GDM and singleton pregnancies in four tertiary care hospitals from 2006 to 2013 in Korea. Biometric parameters were obtained at diagnoses of GDM and within two weeks before delivery. These biometric data were all transformed retrospectively into Z-scores calculated using a reference. Interval changes of values between the two periods were obtained. Multivariable logistic and stepwise backwards regression analyses were performed to develop the most parsimonious predictive model. The prediction model included pre-pregnancy body mass index (BMI), head circumference (HC), Z-score at 24 + 0 to 30 + 6 weeks’ gestation, and abdominal circumference (AC) Z-score at 34 + 0 to 41 + 6 weeks within 2 weeks before delivery. The developed model was then internally validated. Results: Our model’s predictive performance (area under the curve (AUC): 0.925) was higher than estimated fetal weight (EFW) within two weeks before delivery (AUC: 0.744) and the interval change of EFW Z-score between the two periods (AUC: 0.874). It was internally validated (AUC: 0.916). Conclusions: A clinical model was developed and internally validated to predict fetal overgrowth in Korean women with GDM, which showed a relatively good performance.

Gestational diabetes mellitus placentas exhibit epimutations at placental development genes

ABSTRACT Gestational diabetes mellitus (GDM) is a maternal metabolic disorder that perturbs placental development and increases the risk of offspring short- and long-term metabolic disorders. The mechanisms by which GDM impairs placental development remain poorly understood. Here, we defined the DNA methylome of GDM placentas and determined whether GDM perturbs methylation at genes important for placental development. We conducted an epigenome-wide association study of 42 placentas from pregnancies in the South African Soweto First 1000 days cohort (S1000). Using genome-wide bisulfite sequencing, we compared non-GDM placentas to GDM placentas with similar proportions from obese and non-obese mothers. Compared to non-GDM, GDM placentas exhibited a distinct methylation profile consisting of 12,210 differentially methylated CpGs (DMCs) that mapped to 3,875 genes. Epigenetically altered genes were enriched in Wnt and cadherin signalling pathways, both critical in placentation and embryogenesis. We also defined regional DNA methylation perturbation in GDM placentas at 11 placental development genes. These findings reveal extensive changes to the placental epigenome of GDM pregnancies and highlight perturbation enriched at important placental development genes. These molecular changes represent potential mechanisms for GDM-induced placental effects that may serve as candidate biomarkers for placental, maternal, and foetal health. Using a study design that used similar proportions of obese and non-obese mothers in our case and control pregnancies, we minimized the detection of changes due to obesity alone. Further work will be necessary to investigate the extent of the influence of obesity on these GDM-related placental epigenetic changes.