Normal Glucose Tolerance Women Research Articles

Glucometabolic Alterations in Pregnant Women with Overweight or Obesity but without Gestational Diabetes Mellitus: An Observational Study

Introduction: Maternal overweight is a risk factor for gestational diabetes mellitus (GDM). However, emerging evidence suggests that an increased maternal body mass index (BMI) promotes the development of perinatal complications even in women who do not develop GDM. This study aims to assess physiological glucometabolic changes associated with increased BMI. Methods: Twenty-one women with overweight and 21 normal weight controls received a metabolic assessment at 13 weeks of gestation, including a 60-min frequently sampled intravenous glucose tolerance test. A further investigation was performed between 24 and 28 weeks in women who remained normal glucose tolerant. Results: At baseline, mothers with overweight showed impaired insulin action, whereby the calculated insulin sensitivity index (CSI) was lower as compared to normal weight controls (3.5 vs. 6.7 10^-4 min^-1 [microU/mL]^-1, p = 0.025). After excluding women who developed GDM, mothers with overweight showed higher average glucose during the oral glucose tolerance test (OGTT) at the third trimester. Moreover, early pregnancy insulin resistance and secretion were associated with increased placental weight in normal glucose-tolerant women. Conclusion: Mothers with overweight or obesity show an unfavorable metabolic environment already at the early stage of pregnancy, possibly associated with perinatal complications in women who remain normal glucose tolerant.

Pregnancy outcomes of women with untreated ‘mild’ gestational diabetes (gestational diabetes by the WHO 2013 but not by the WHO-1999 diagnostic criteria) – A population-based cohort study

AimsWe compared pregnancy outcomes of untreated ‘mild’ GDM (GDM by WHO 2013 but not by WHO-1999) to normal glucose tolerant women (NGT). MethodsIn a universal screening program 4333 pregnant women had a 3-point 75 g OGTT in Hungary in 2009–2013. By WHO-2013 untreated NGT was diagnosed in n = 3303, ‘mild’ GDM in n = 336 cases. Results‘Mild’ GDM women were older (mean difference, SE: 1.4, 0.3 yrs), had higher fasting (1.0, 0.02), 60-minute (1.0, 0.09), and 120-minute (0.4, 0.06 mmol/l) blood glucose, and blood pressure (2.6, 0.5/2.0, 0.5 mmHg). Weight gain was similar in both groups (−0.3, 0.3 kg). GDM newborns were heavier (142, 50 g) and were more frequently macrosomic (>4000 g, OR 1.85, 95 %CI 1.35–2.54). Hypertension during pregnancy was more prevalent in the GDM group (OR 1.55, 95 %CI 1.05–2.28), as well as induced (OR 1.38, 95 %CI 1.10–1.74) and instrumental delivery (OR 1.34, 95 %CI 1.07–1.68), and acute caesarean section (OR 1.32, 95 %CI 1.04–1.64). Most of these differences substantially attenuated or became non-significant after adjustment for pre-pregnancy BMI. ConclusionsPregnancy outcomes of ‘mild’ GDM were worse compared to normal glucose tolerant women however these differences were explained by the pre-pregnancy BMI difference between groups.

One abnormal value or vomiting after oral glucose tolerance test in pregnancy: incidence and impact on maternal-fetal outcomes

Objective To analyze pregnancy outcomes of women with one abnormal value (OAV) during oral glucose tolerance test (OGTT) or OGTT-intolerance, compared with gestational diabetes mellitus (GDM) and normal glucose tolerance (NGT) pregnant women, according to whether they received any health intervention or not. Methods An observational retrospective study was designed including pregnant women who gave birth at Hospital del Mar, Barcelona (Spain) during December/2014–July/2018. Baseline characteristics, pregnancy outcomes and health interventions were obtained from a database collected previously for other study. Inclusion criteria were singleton pregnancies with OAV or OGTT-intolerants who gave birth at the Hospital. GDM screening followed a two-step approach: 50 g O’Sullivan test and 100 g 3-hour OGTT if the former was abnormal. Results From a total of 2,662 pregnancies, 326 (12.2%) had GDM, 87 OAV (3.3%), 65 OGTT intolerance (2.4%) and 2,184 were NGT women. First trimester HbA1c in both OAV and OGTT-intolerant women was significantly higher than in NGT group, and significantly lower than in GDM pregnants. No differences in obstetric outcomes were found between OGTT-intolerants and NGT/GDM groups. Treated OGTT-intolerants had greater gestational age at delivery than non-treated ones (weeks, 39.6 ± 1.2 vs 38.0 ± 4.0, respectively). In OAV women, significant differences were observed in newborns’ birthweight (g, 3227.3 ± 500.8 vs 3351.1 ± 436.7, vs GDM) and gestational age at birth (weeks, 38.7 ± 1.8 vs 39.3 ± 1.9, vs NGT), but not in macrosomia/pre-eclampsia. No differences were found according to treatment in OAV. Conclusions OAV and OGTT-intolerants account for a third of pregnant women referred to Diabetes Unit. Their rates of preterm birth, pre-eclampsia and macrosomia were not different from NGT or GDM women.

Weight progression and adherence to weight gain target in women with vs. without gestational diabetes: a retrospective cohort study

BackgroundWeight management has been an important component of the service in obstetric care offered to pregnant women. Current gestational weight gain recommendations were primarily for the general obstetric population, raising concern about the applicability to women with gestational diabetes mellitus (GDM). We aimed to assess the difference in weight progression and adherence to the recommended gestational weight gain targets between women with gestational diabetes mellitus (GDM) and women with normal glucose tolerance (NGT).MethodsThis was a hospital-based retrospective study of 56,616 pregnant women (9,430 GDM women and 47,186 NGT women) from Guangzhou between 2017 and 2021. The average change in weight progression was estimated based on serial weight measurements throughout pregnancy, using a mixed effects model with a random intercept to account for repeated measures of the same individual.ResultsWomen with GDM gained less weight (12.07 [SD 5.20] kg) than women with NGT (14.04 [SD 5.04] kg) throughout pregnancy. Before OGTT, a small difference was observed in the average change in weight progression between the two groups (GDM, 0.44 kg/week vs. NGT, 0.45 kg/week, p < 0.001), however, this gap widened significantly after the test (0.34 vs. 0.50 kg/week, p < 0.001). GDM individuals were identified with an approximately 4-fold increased proportion of insufficient weight gain (41.1% vs. 10.4%) and a 2-fold decreased proportion of excessive weight gain (22.6% vs. 54.2%) compared to NGT individuals. These results were consistently observed across different BMI categories, including underweight (insufficient: 52.7% vs. 19.9%; excessive: 15.6% vs. 35.3%), normal weight (insufficient 38.2% vs. 7.4%; excessive: 22.2% vs. 57.3%), and overweight/obese (insufficient: 43.1% vs. 9.8%; excessive: 30.1% vs. 68.8%).ConclusionWeight progression varied significantly between GDM and NGT individuals, resulting in a substantial difference in identifying insufficient and excessive weight gain between the two groups under current gestational weight gain guidelines.

Normal glucose tolerant women with low glycemia during the oral glucose tolerance test have a higher risk to deliver a low birth weight infant.

Data are limited on pregnancy outcomes of normal glucose tolerant (NGT) women with a low glycemic value measured during the 75g oral glucose tolerance test (OGTT). Our aim was to evaluate maternal characteristics and pregnancy outcomes of NGT women with low glycemia measured at fasting, 1-hour or 2-hour OGTT. The Belgian Diabetes in Pregnancy-N study was a multicentric prospective cohort study with 1841 pregnant women receiving an OGTT to screen for gestational diabetes (GDM). We compared the characteristics and pregnancy outcomes in NGT women according to different groups [(<3.9mmol/L), (3.9-4.2mmol/L), (4.25-4.4mmol/L) and (>4.4mmol/L)] of lowest glycemia measured during the OGTT. Pregnancy outcomes were adjusted for confounding factors such as body mass index (BMI) and gestational weight gain. Of all NGT women, 10.7% (172) had low glycemia (<3.9 mmol/L) during the OGTT. Women in the lowest glycemic group (<3.9mmol/L) during the OGTT had compared to women in highest glycemic group (>4.4mmol/L, 29.9%, n=482), a better metabolic profile with a lower BMI, less insulin resistance and better beta-cell function. However, women in the lowest glycemic group had more often inadequate gestational weight gain [51.1% (67) vs. 29.5% (123); p<0.001]. Compared to the highest glycemia group, women in the lowest group had more often a birth weight <2.5Kg [adjusted OR 3.41, 95% CI (1.17-9.92); p=0.025]. Women with a glycemic value <3.9 mmol/L during the OGTT have a higher risk for a neonate with birth weight < 2.5Kg, which remained significant after adjustment for BMI and gestational weight gain.

Risk of fetal undergrowth in the management of gestational diabetes mellitus in Japan.

In Japan, the increasing frequency of underweight among women of reproductive age and the accompanying increase in the rate of low birth weight (LBW) are social issues. The study aimed to establish a prospective registry system for gestational diabetes mellitus (GDM) in Japan and to clarify the actual status of GDM according to the International Association of Diabetes and Pregnancy Study Groups (IADPSG) criteria. Pregnant women with gestational diabetes mellitus and those in the normal glucose tolerance (NGT) group were enrolled in the Diabetes and Pregnancy Outcome for Mother and Baby study from October 2015. Pregnant women with positive glucose screening in early and mid-to-late pregnancy underwent a 75 g oral glucose tolerance test by gestational week 32. Gestational diabetes mellitus was diagnosed according to IADPSG criteria. Women with a positive glucose screening test at mid-to-late pregnancy but NGT were enrolled as references (NGT group). Treatment for gestational diabetes mellitus and maternal and neonatal pregnancy data were prospectively collected on outcomes. In total 1,795 singleton pregnancies (878 women with GDM and 824 NGT women) were analyzed. The risk of LBW and small-for-gestational age in the GDM group was significantly higher than in the NGT group. A similar relationship was found for LBW risk in the non-overweight/obese group but not in the overweight/obese group. We established a prospective GDM registry system in Japan. In the management of GDM in Japan, suppression of maternal weight gain may be associated with reduced fetal growth, especially in non-overweight/obese women with GDM; however, further investigation is required.

Effect of maternal body mass index on the steroid profile in women with gestational diabetes mellitus.

To explore the effect of maternal body mass index (BMI) on steroid hormone profiles in women with gestational diabetes mellitus (GDM) and those with normal glucose tolerance (NGT). We enrolled 79 women with NGT and 80 women with GDM who had a gestational age of 24-28 weeks. The participants were grouped according to their BMI. We quantified 11 steroid hormones profiles by liquid chromatography-tandem mass spectrometry and calculated the product-to-precursor ratios in the steroidogenic pathway. Women with GDM and BMI<25kg/m2 showed higher concentrations of dehydroepiandrosterone (DHEA) (p<0.001), testosterone (T) (p=0.020), estrone (E1) (p=0.010) and estradiol (E2) (p=0.040) and lower Matsuda index and HOMA-β than women with NGT and BMI<25kg/m2. In women with GDM, concentrations of E1 (p=0.006) and E2 (p=0.009) declined, accompanied by reduced E2/T (p=0.008) and E1/androstenedione (A4) (p=0.010) in the BMI>25 kg/m2 group, when compared to that in the BMI<25 kg/m2 group. The values of E2/T and E1/A4 were used to evaluate the cytochrome P450 aromatase enzyme activity in the steroidogenic pathway. Both aromatase activities negatively correlated with the maternal BMI and positively correlated with the Matsuda index in women with GDM. NGT women and GDM women with normal weight presented with different steroid hormone profiles. Steroidogenic pathway profiling of sex hormones synthesis showed a significant increase in the production of DHEA, T, E1, and E2 in GDM women with normal weight. Additionally, the alteration of steroid hormone metabolism was related to maternal BMI in women with GDM, and GDM women with overweight showed reduced estrogen production and decreased insulin sensitivity compared with GDM women with normal weight.

Low Gestational Weight Gain in Women With Gestational Diabetes Is Safe With Better Metabolic Profile Postpartum.

More data are needed on the potential benefits and risks of gestational weight gain (GWG) less than recommended and excessive GWG in women with gestational diabetes (GDM) compared to women with normal glucose tolerance (NGT) during pregnancy. This work aimed to evaluate association of gestational weight gain (GWG) as low, within, or above (excessive) according to Institute of Medicine (IOM) guidelines, with pregnancy outcomes in women with gestational diabetes (GDM) and normal glucose tolerance (NGT). This prospective cohort study included 7 Belgian hospitals and 1843 women receiving universal GDM screening with a 75-g oral glucose tolerance test. Pregnancy outcomes and postpartum characteristics were the main outcome measures. Women with GDM and low GWG (n = 97, 52.4%) had similar rates of small-for-gestational age infants and preterm delivery, were less often overweight or obese postpartum (35.7% [30] vs 56.5% [26]; P < .022) and less often had postpartum weight retention (PPWR) (48.8% [41] vs 87.9% [40]; P < .001) compared to GWG within range (n = 58, 31.3%). GDM with excessive GWG (n = 30, 16.2%) more often had neonatal hypoglycemia (30.8% (8) vs 5.9% [3], aOR 7.15; 95% CI, 1.52-33.63; P = .013) compared to GWG within range. NGT with excessive GWG (28.3% [383]) more often had instrumental delivery (15.9% [61] vs 11.9% [64], aOR 1.53; 95% CI, 1.03-2.27; P = .035) and more large-for-gestational age infants (19.3% [74] vs 10.4% [56], aOR 1.67; 95% CI, 1.13-2.47; P = .012) compared to GWG within range. GWG below IOM guidelines occurred frequently in GDM women, without increased risk for adverse pregnancy outcomes and with better metabolic profile postpartum. Excessive GWG was associated with increased risk for neonatal hypoglycemia and worse metabolic profile postpartum in women with GDM, and with higher rates of LGA and instrumental delivery in NGT women.

Do pregnancy outcomes of women with false-positive early gestational diabetes mellitus differ from those of women with normal glucose tolerance?

BackgroundTo investigate whether false-positive early gestational diabetes mellitus (GDM) women can be managed similarly as normal glucose tolerance (NGT) women.MethodsThis retrospective study was conducted at a tertiary care center in Japan. Pregnancy and neonatal outcomes of 67 singleton pregnancies with false-positive early GDM and 1774 singleton pregnancies with NGT who delivered after 22 weeks of gestation were compared. GDM was diagnosed according to the International Association of Diabetes and Pregnancy Study Groups (IADPSG) criteria (patients having one or more of the following: fasting plasma glucose ≥ 92 mg/dL and a 75 g oral glucose tolerance test (OGTT) value ≥ 180 mg/dL at 1 h, or ≥ 153 mg/dL at 2 h). Pregnant women diagnosed with GDM in early pregnancy who did not meet the diagnostic criteria on the second OGTT were defined as having false-positive early GDM. Women with false-positive early GDM did not receive any therapeutic intervention during gestation.ResultsMaternal age, pre-pregnancy body mass index, and gestational weight gain were significantly higher in the false-positive GDM group than in the NGT group. No significant differences were found in pregnancy outcomes, including gestational age, birth weight, large for gestational age rate, and cesarean delivery rate. Except for a higher neonatal hypoglycemia rate in the false-positive early GDM group, no significant differences were found in neonatal outcomes.ConclusionsThere were no clinically significant differences between early GDM false-positive women exhibiting GDM patterns only during early pregnancy and NGT women. False-positive early GDM women can be managed similarly as NGT women, suggesting that World Health Organization diagnostic guidelines, applying the IADPSG criteria during early pregnancy, need revision.

Can the First Fasting Plasma Glucose Test in Pregnancy Predict Subsequent Gestational Complications?

Objective To determine the best cut-off level of pregnant women's first fasting plasma glucose (FFPG) test results for the prediction of subsequent onset of gestational diabetes mellitus (GDM) and to examine the association between FFPG and maternal and neonatal outcomes in a large Caucasian population. Methods 1437 medical records of women with singleton pregnancies followed up between 2015 and 2018 were retrospectively analyzed. Data on FFPG tested in the first trimester and 75 g oral glucose tolerance test (OGTT) findings performed according to IADPSG criteria and Italian guidelines were collected and evaluated. The women's clinical and metabolic characteristics (age, prepregnancy body mass index (BMI), previous pregnancies complicated by GDM, timing of delivery, and gestational hypertension) were also recorded. The fetal variables considered were being large for gestational age (LGA) or small for gestational age (SGA), macrosomia, and hypoglycemia. Results Among the 1437 pregnant women studied, 684 had a normal glucose tolerance (NGT) and 753 developed GDM. In a univariate analysis FFPG ≥92 mg/dl predicts the risk of GDM with an OR = 2.36 (95% CI 1.930–3.186; p < 0.001). In multivariate analysis, after adjusting for principal risk factors of GDM (BMI, previous GDM, age >35 years, family history of diabetes) FFPG ≥92 mg/dl was associated with the risk of GDM (OR = 1.92; 95% CI 1.488–2.492; p < 0.001). In univariate analysis, FFPG ≥92 mg/dl predict the risk of insulin therapy in GDM women with a OR = 1.88 (95% CI 1.230–2.066; p < 0.001). As regards LGA, in a multivariate analysis, after adjusting for BMI, FFPG ≥92 mg/dl was associated with the risk of LGA only in NGT women (OR = 2.34; 95% CI 1.173–4.574; p=0.014), but not in GDM women. FFPG was not associated with other maternal or neonatal outcomes. Conclusions FFPG ≥92 mg/dl is related to GDM diagnosis and to the need of insulin therapy if GDM is diagnosed. An early diagnosis and a prompt start of insulin therapy are essential to prevent maternal and fetal complications.

Vitamin B12 and Folate Markers Are Associated with Insulin Resistance During the Third Trimester of Pregnancy in South Asian Women, Living in the United Kingdom, with Gestational Diabetes and Normal Glucose Tolerance

BackgroundGestational diabetes mellitus (GDM) can adversely affect the health of the developing fetus. Women of South Asian origin are particularly at risk of developing GDM. Insulin resistance (IR) contributes to the etiology of GDM, and although studies have shown associations of vitamin B12 (B12) and folate status with GDM and IR, only a limited number of B12 and folate markers have been used. ObjectiveWe used a comprehensive panel of B12 and folate markers to examine their association with IR in pregnant women with diet-controlled GDM and normal glucose tolerance (NGT). MethodsIn this cross-sectional study, 59 British-Bangladeshi women (24 GDM and 35 NGT) with a mean age of 29 y, BMI (in kg/m2) 26.7 and gestational age 33 wk were recruited. Serum total B12, holotranscobalamin, folate, methylmalonic acid, plasma homocysteine, 5-methyltetrahydrofolate, and red cell folate (RCF) were measured along with other parameters. The independent sample t-test and chi-squared test were used to assess differences in markers between GDM and NGT women. Spearman's test was used to look for correlations. A simple multiple regression analysis was used to investigate if markers of B12 and folate status predicted IR, using the HOMA-IR and adjusting for age, GDM status, and BMI. ResultsThere were no differences in concentrations of B12 and folate markers between GDM and NGT women. In Spearman's analysis HOMA-IR correlated negatively with total serum B12 (P < 0.001) and holotranscobalamin (P < 0.05), and positively with BMI (P < 0.001), blood pressure (P < 0.05) and triglycerides (P < 0.05) in all women. MMA did not correlate with any of the B12 markers. In regression analysis, total B12 (β = −0.622, P = 0.004), RCF (β = 0.387, P = 0.018), and BMI (β = 0.024, P < 0.001) were the significant predictors of HOMA-IR variance. ConclusionsSignificant associations between markers of B12 and folate status with HOMA-IR were found during the third trimester in British-Bangladeshi women. B12 markers correlated poorly with each other.

Association of Plasma Fibrinogen and Insulin Resistance in Women with Gestational Diabetes Mellitus

Gestational diabetes mellitus (GDM) is thought to be developed as a consequence of high insulin resistance (IR). It has been proposed that IR may involve in the pathogenesis of hyperfibrinogenemia in GDM. This study was aimed to evaluate the plasma fibrinogen levels and its association with insulin resistance in GDM. This cross sectional study was performed with 44 GDM women and 44 pregnant women with normal glucose tolerance (NGT) at or after 24 weeks of their gestation. Glucose was measured by glucose oxidase method, fasting insulin was measured by chemiluminescent immunoassay and plasma fibrinogen was measured by STA-fibrinogen kit with an automated coagulation analyzer. GDM women had significantly increased age and higher BMI than pregnant women with NGT (p=0.008). Plasma fibrinogen level was significantly higher in GDM (p<0.001). Fasting insulin level and Homeostasis Model Assessment of Insulin Resistance [HOMA-IR] were also significantly higher in GDM (p<0.001). Fibrinogen showed positive correlation with fasting insulin level (r=0.470, p<0.001) as well as with HOMA-IR (r=0.470, p<0.001) in GDM. Using HOMA-IR at cut-off value 2.89, it was observed that a significant number of GDM women had higher HOMA-IR values than pregnant women with NGT (p=0.002) and GDM women with HOMA-IR values ≥2.89 had significantly higher fibrinogen values (p=0.002). Gestational diabetes mellitus is associated with higher plasma fibrinogen level and increased insulin resistance, indicating a state of hypercoagulability than that of pregnant women with normal glucose tolerance. There is a clear association between hyperfibrinogenemia and insulin resistance.

Plasma glycated CD59 predicts postpartum glucose intolerance after gestational diabetes.

To assess whether in women with gestational diabetes mellitus (GDM), postpartum plasma glycated CD59 (pGCD59) levels predict conversion to glucose intolerance diagnosed with an oral glucose tolerance test (OGTT). Blood levels of pGCD59 were measured in a case-control study of 105 women with GDM who underwent a 75 g OGTT 3 months postpartum. The 35 postpartum glucose intolerant cases were individually matched for age, BMI, ethnic origin, and parity with 70 women with GDM but normal postpartum OGTT (controls). The GDM cohort (105) was also matched with 105 normal glucose tolerant women during pregnancy. pGCD59 was measured by ELISA in standard peptide units (SPU). Mean pGCD59 postpartum was significantly higher in cases than in controls (1.5 ± 0.6 SPU vs 1.0 ± 0.6 SPU, P < 0.001). The area under the receiving operating characteristic curve (AUC) in cases vs controls was 0.72 (95% CI: 0.62-0.83) for postpartum pGCD59 and 0.50 (95% CI: 0.36-0.61) for postpartum HbA1c. A 0.5-unit increase in postpartum pGCD59 was associated with an odds ratio (OR) of 3.3 (95% CI: 1.82-6.16, P < 0.001) for glucose intolerance postpartum. A pGCD59 cut-off postpartum of 0.9 SPU had a sensitivity of 85.7% (95% CI: 69.7-95.2%), specificity of 47.8% (95% CI: 35.6-60.2%), positive predictive value of 45.4% (95% CI: 33.1-58.2%), and negative predictive value of 86.8% (95% CI: 71.9-95.6%). pGCD59 in pregnancy was a poor predictor for glucose intolerance postpartum (AUC of 0.61 (95% CI: 0.50-0.72)). pGCD59 might identify women at low risk for glucose intolerance postpartum and could help to avoid an OGTT.

Predictors of neonatal adiposity and associations by fetal sex in women with gestational diabetes mellitus and normal glucose-tolerant women

The key findings of this multi-centre prospective cohort study were that neonates born to mothers treated for Gestational diabetes mellitus (GDM) (by lifestyle or medication, e.g. insulin or metformin) had high rates of macrosomia but similar adiposity to those born of mothers with normal glucose tolerance. In contrast, neonates born to untreated mothers who were overweight and had a normal glucose tolerance had increased adiposity. Increased gestational weight gain was associated with increased neonatal adiposity in boys. Maternal BMI, fasting blood glucose, triglycerides and gestational weight gain were independent predictors for neonatal adiposity.

Early Onset Acceleration of Fetal Growth in Gestational Diabetes Mellitus: Deciding About When and Whom to Screen for Preventing Fetal Macrosomia

The precise time into pregnancy at which women are screened for gestational diabetes mellitus (GDM) is crucial for determining the benefits of diagnosis. However, this issue remains a source of intense debate among guidance authorities and there is no consensus about when and whom to screen. Since 2010, the IADPSG recommends universal screening with 75g OGTT at 24–28 weeks’ gestation (WG), due to evidence of a positive linear correlation between maternal blood glucose levels around 28 WG and risk of fetal macrosomia. Nonetheless, emerging evidence indicates that initial acceleration of fetal growth (FG) related to GDM, predicting fetal macrosomia, is already underway at 20 WG, thereby suggesting that screening strategies for GDM earlier than the recommended 24–28 WG should be reconsidered (1). By exploiting the routine 19–21 WG obstetrical assessment of FG (anomaly scan), along with the risk stratification system endorsed by the Italian NHS, which offers, in addition to the usual GDM screening test at 24–28 WG, an early 75g OGTT at 16–18 WG to women who are classified as at high risk (HR) for GDM (i.e. previous GDM, pre-gravid obesity, or FPG at first prenatal visit between 5.6–6.9 mmol/L), we aimed to verify whether an early onset acceleration of FG related to GDM would be observed in our pregnant population, and if reversion could occur with current screening recommendations. For this, 769 consecutive women in singleton pregnancies, subjected to both anomaly scan and GDM screening, were retrospectively enrolled at our Institution between Jan 2018-Feb 2020. At a mean time of 20.8 WG, the percentiles of estimated fetal weight (EFW) and abdominal circumference (AC) were significantly higher in women who tested positive for GDM at late screening than in women with normal glucose tolerance (NGT). However, while no differences in the birthweight (BW) percentiles of neonates born to non-HR women diagnosed with GDM at 24–28 WG, with respect to NGT women were observed (p=0.416), neonates born to HR women diagnosed with GDM at 24–28 WG (due to refusal to comply with early screening advices) were significantly heavier (p<0.001). In contrast, both the EFW and AC percentiles, as well as the BW percentiles, were significantly lower in infants born to HR women diagnosed with GDM at 16–18 WG with respect to their late diagnosis counterparts (EFW p=0.001, AC p=0.002, BW p=0.048), and not dissimilar to those of NGT women (EFW p=0.824, AC p=0.873, BW p=0.242). These results were confirmed by regression analysis, while adjusting for maternal confounders. Although an initial acceleration of FG related to GDM can be detected at anomaly scan in non-HR women, reversion occurs with current screening recommendations. Earlier screening strategies should be reserved to HR women, as the acceleration of FG related to GDM in these cases is less responsive to treatment delays. (1) Ref: Li et al. Lancet Diabetes Endocrinol. 2020;8(4):292–300.

Antenatal Depression and Risk of Gestational Diabetes, Adverse Pregnancy Outcomes, and Postpartum Quality of Life

To determine the impact of depressive symptoms on pregnancy outcomes and postpartum quality of life in women with gestational diabetes mellitus (GDM) and normal glucose tolerance (NGT). 1843 women from a prospective cohort study received universal GDM screening with an oral glucose tolerance test (OGTT). The Center for Epidemiologic Studies - Depression questionnaire was completed before GDM diagnosis was communicated, and in GDM women in early postpartum. All participants completed the SF-36 health survey postpartum. Women who developed GDM (231; 12.5%) had significantly more often depressive symptoms than NGT (1612; 87.5%) women [21.3% (48) vs. 15.1% (239), OR 1.52, 95% CI (1.08-2.16), p=0.017]. Compared to GDM women without depressive symptoms, depressed GDM women attended less often the postpartum OGTT [68.7% (33) vs. 87.6% (155), p=0.002], remained more often depressed [37.1% (13) vs. 12.4% (19), p<0.001] and had lower SF-36 scores postpartum. There were no significant differences in pregnancy outcomes between both groups. Rates of labor inductions were significantly higher in the NGT group with depressive symptoms compared to the non-depressed NGT group [31.7% (75) vs. 24.7% (330), aOR 1.40, 95% CI (1.01-1.93), p=0.041]. NGT women with depressive symptoms had lower SF-36 scores (p<0.001) postpartum compared to non-depressed NGT women. Women with antenatal symptoms of depression develop more often GDM. GDM women with depressive symptoms remain more often depressed postpartum with lower quality of life. NGT women with depressive symptoms have higher rates of labor inductions and lower quality of life postpartum compared to non-depressed NGT women.

Maternal Diabetes Impairs Insulin and IGF-1 Receptor Expression and Signaling in Human Placenta

BackgroundMaternal high blood glucose during pregnancy increases the risk for both maternal and fetal adverse outcomes. The mechanisms underlying the regulator effects of hyperglycemia on placental development and growth have not been fully illustrated yet. The placenta expresses high amounts of both insulin receptor (IR) and insulin-like growth factor receptor (IGF-1R). It has been reported that the placenta of diabetic women has structural and functional alterations and the insulin/IGF system is likely to play a role in these changes. The aim of the present study was to measure the content of IR and IGF-1R and their phosphorylation in the placenta of women with type 1 diabetes mellitus (T1D) or with gestational diabetes mellitus (GDM) compared to women with normal glucose tolerance (NGT) during pregnancy.MethodsPlacental tissues were obtained from 80 Caucasian women with a singleton pregnancy. In particular, we collected placenta samples from 20 T1D patients, 20 GDM patients and 40 NGT women during pregnancy. Clinical characteristics and anthropometric measures of all women as well as delivery and newborn characteristics were recorded. Patients were also subdivided on the basis of peripartum glycemia either ≥90 mg/dl or <90 mg/dl, regardless of the diagnosis.ResultsIn T1D patients, a higher rate of adverse outcomes was observed. Compared to the GDM women, the T1D group showed significantly higher average capillary blood glucose levels at the third trimester of pregnancy and at peripartum, and higher third-trimester HbA1c values. In both T1D and GDM women, HbA1c values during pregnancy correlated with glucose values in the peripartum period (R-squared 0.14, p=0.02). A positive correlation was observed between phosphorylation of placental IR and the glucose levels during the third trimester of GDM and T1D pregnancy (R-squared 0.21, p=0.003). In the placenta of T1D patients, IGF-1R phosphorylation and IR isoform A (IR-A) expression were significantly increased (p=0.006 and p=0.040, respectively), compared to the NGT women. Moreover, IGF-1R phosphorylation was significantly increased (p<0.0001) in the placenta of patients with peripartum glucose >90 mg/dl, while IR-A expression was increased in those with peripartum blood glucose higher than 120 mg/dl (p=0.046).ConclusionsTo the best of our knowledge, our study represents the first one in which an increased maternal blood glucose level during pregnancy is associated with an increased IGF-1R phosphorylation and IR-A expression in the placenta. Both these mechanisms can promote an excessive fetal growth.

Contribution of Gestational Weight Gain on Maternal Glucose Metabolism in Women with GDM and Normal Glucose Tolerance.

ContextEfforts to decrease the risk of developing metabolic complications of pregnancy such as gestational diabetes (GDM) through lifestyle intervention (decreasing excessive gestational weight gain (GWG)) during pregnancy have met with limited success.ObjectiveThe purpose of this study was to determine the relationship between the longitudinal changes in weight/body composition and insulin sensitivity and response in women with normal glucose tolerance (NGT) and those who developed GDM.DesignWe conducted a secondary analysis of a prospective cohort developed before conception and again at 34 to 36 weeks gestation. A total of 29 NGT and 17 GDM women were evaluated for longitudinal changes in insulin sensitivity/response using the hyperinsulinemic-euglycemic clamp and an IV-glucose tolerance test. Body composition was estimated using hydrodensitometry. Both absolute change (Δ) and relative change (%Δ) between these 2 time points were calculated. We performed simple and multiple linear regression analysis to assess the relationship between GWG and measures of glucose metabolism, ie, insulin sensitivity and response.ResultsBased on the primary study design there was no significant difference in clinical characteristics between women with NGT and those developing GDM. Prior to pregnancy, women who developed GDM had lower insulin sensitivity levels (P = 0.01) compared with NGT women. Absolute change and %Δ in insulin sensitivity/insulin response and body weight/body composition were not significantly different between NGT and GDM women. Changes in body weight contributed to only 9% of the Δ in insulin sensitivity both in women developing GDM and NGT women.ConclusionsThese data suggest that other factors—such as maternal pre-pregnancy insulin sensitivity and placental derived factors affecting insulin sensitivity—rather than maternal GWG account for the changes in glucose metabolism during human pregnancy.

Predictors of neonatal adiposity and associations by fetal sex in women with gestational diabetes mellitus and normal glucose-tolerant women.

To determine predictors of neonatal adiposity and differences in associations by fetal sex in women with gestational diabetes mellitus (GDM), normal-weight and overweight (BMI ≥ 25kg/m2) normal glucose-tolerant women (NGT). Skinfold thickness was measured in 576 newborns, and cord blood leptin, c-peptide and lipids in 327 newborns in a multi-centric prospective cohort study. Compared to neonates of normal-weight NGT women (327), neonates of women with GDM (97) were more often large-for-gestational age (LGA) (16.5% vs 8.6%, p = 0.024) ,but the macrosomia rate (8.2% vs 5.8%, p = 0.388), sum of skinfolds (13.9mm ± 2.9 vs 13.3mm ± 2.6, p = 0.067), neonatal fat mass (1333.0g ± 166.8 vs 1307.3g ± 160.9, p = 0.356), and cord blood biomarkers were not significantly different. Compared to neonates of normal-weight NGT women, neonates of overweight NGT women (152) had higher rates of macrosomia (12.5% vs 5.8%, p = 0.012), LGA (17.1% vs 8.6%, p = 0.006), higher sum of skinfolds (14.3mm ± 2.6 vs 13.2mm ± 2.6, p < 0.001), neonatal fat mass (1386.0g ± 168.6 vs 1307.3g ± 160.9, p < 0.001), % neonatal fat mass > 90th percentile (15.2% vs 7.1%, p < 0.001), without significant differences in cord blood biomarkers. Maternal BMI, fasting glycemia, triglycerides, gestational weight gain, cord blood leptin ,and cord blood triglycerides were independent predictors for neonatal adiposity. Gestational weight gain was positively associated with adiposity in boys only. Compared to neonates of normal-weight NGT women, neonates of GDM women have higher LGA rates but similar adiposity, while neonates of overweight NGT women have increased adiposity. Limiting gestational weight gain might be especially important in the male fetus to reduce neonatal adiposity.

The impact of antenatal depression on pregnancy outcomes in women with gestational diabetes mellitus and normal glucose tolerant women

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)