Late-onset Gestational Diabetes Mellitus Research Articles

Retrospective cohort study on treatment outcomes of early vs late onset gestational diabetes mellitus.

Gestational diabetes mellitus (GDM) affects roughly 14% of pregnancies, its prevalence is increasing, and it is associated with a significant risk of complications for both mother and offspring. A high proportion of women with GDM can be detected early in pregnancy. In Italy, early GDM screening occurs in a selective way, as it is performed only in the presence of important risk factors. It remains to be elucidated not only how and when to diagnose early GDM but especially whether to treat it. This study aimed to compare the characteristics and complications of early vs late GDM as assessed and treated in a real-world setting, according to the Italian guidelines of the Istituto Superiore di Sanità. We conducted a retrospective cohort study in women with GDM delivering singletons between 2017 and 2021. Women with early GDM had higher BMI and a higher proportion of Middle Eastern or African women. Early GDM was independently associated with the use of insulin (p < 0.001). It required also higher doses of insulin, possibly due to the higher BMI. Early GDM was also independently associated with higher post-prandial (after dinner) glucose levels during the 3° trimester (p = 0.04). Nevertheless, early GDM women achieved glucose targets and put on less weight during gestation. Early GDM was independently associated with preeclampsia (p = 0.05). Otherwise, there were no other differences between early and late GDM in terms of pregnancy complications. After delivery, early GDM was independently associated with abnormal glucose tolerance. Early GDM women exhibited more severe GDM features. However, after achieving recommended glucose and body weight targets, there were no substantial differences between early and late GDM in terms of pregnancy complications apart from preeclampsia. These data support diagnosis and treatment of women with early GDM.

Analysis of early-pregnancy metabolome in early- and late-onset gestational diabetes reveals distinct associations with maternal overweight.

It is not known whether the early-pregnancy metabolome differs in patients with early- vs late-onset gestational diabetes mellitus (GDM) stratified by maternal overweight. The aims of this study were to analyse correlations between early-pregnancy metabolites and maternal glycaemic and anthropometric characteristics, and to identify early-pregnancy metabolomic alterations that characterise lean women (BMI <25 kg/m2) and women with overweight (BMI ≥25 kg/m2) with early-onset GDM (E-GDM) or late-onset GDM (L-GDM). We performed a nested case-control study within the population-based prospective Early Diagnosis of Diabetes in Pregnancy cohort, comprising 210 participants with GDM (126 early-onset, 84 late-onset) and 209 normoglycaemic control participants matched according to maternal age, BMI class and primiparity. Maternal weight, height and waist circumference were measured at 8-14 weeks' gestation. A 2 h 75 g OGTT was performed at 12-16 weeks' gestation (OGTT1), and women with normal results underwent repeat testing at 24-28 weeks' gestation (OGTT2). Comprehensive metabolomic profiling of fasting serum samples, collected at OGTT1, was performed by untargeted ultra-HPLC-MS. Linear models were applied to study correlations between early-pregnancy metabolites and maternal glucose concentrations during OGTT1, fasting insulin, HOMA-IR, BMI and waist circumference. Early-pregnancy metabolomic features for GDM subtypes (participants stratified by maternal overweight and gestational timepoint at GDM onset) were studied using linear and multivariate models. The false discovery rate was controlled using the Benjamini-Hochberg method. In the total cohort (n=419), the clearest correlation patterns were observed between (1) maternal glucose concentrations and long-chain fatty acids and medium- and long-chain acylcarnitines; (2) maternal BMI and/or waist circumference and long-chain fatty acids, medium- and long-chain acylcarnitines, phospholipids, and aromatic and branched-chain amino acids; and (3) HOMA-IR and/or fasting insulin and L-tyrosine, certain long-chain fatty acids and phospholipids (q<0.001). Univariate analyses of GDM subtypes revealed significant differences (q<0.05) for seven non-glucose metabolites only in overweight women with E-GDM compared with control participants: linolenic acid, oleic acid, docosapentaenoic acid, docosatetraenoic acid and lysophosphatidylcholine 20:4/0:0 abundances were higher, whereas levels of specific phosphatidylcholines (P-16:0/18:2 and 15:0/18:2) were lower. However, multivariate analyses exploring the early-pregnancy metabolome of GDM subtypes showed differential clustering of acylcarnitines and long-chain fatty acids between normal-weight and overweight women with E- and L-GDM. GDM subtypes show distinct early-pregnancy metabolomic features that correlate with maternal glycaemic and anthropometric characteristics. The patterns identified suggest early-pregnancy disturbances of maternal lipid metabolism, with most alterations observed in overweight women with E-GDM. Our findings highlight the importance of maternal adiposity as the primary target for prevention and treatment.

Fasting blood glucose as a screening measure for late-onset gestational diabetes in the third trimester.

To investigate the positive rate of late-onset gestational diabetes mellitus (GDM) by additional fasting blood glucose (FBG) screening at 32-34 gestational weeks (GW) and analyse the perinatal outcomes of late-onset GDM after standard treatment. An Prospective cohort study. Single centre in China. 1130 singleton pregnancies with negative GDM screening in their first and second trimester. Additional FBG testing was performed at 32-34 GW. Pregnancies with FBG ≥5.1 mmol/L were diagnosed as GDM and received standardized treatment. Perinatal outcomes were collected and compared. Diagnosis of late-onset GDM, obstetric and neonatal outcomes. 6.3% (71/1130) of participants had FBG values ≥5.1 mmol/L and were diagnosed with late-onset GDM. Sixty-five (91.5%) were treated by dietary therapy and 6 (8.5%) by insulin therapy. The perinatal outcomes of full-term delivery were compared. The incidence of macrosomia (22.7% vs. 5.1%, adjusted odds ratio (aOR) 5.51, 95% confidence interval (CI) 1.83-16.61, p = 0.002) and NICU transferring (18.3% vs. 10.1%, aOR 1.94, 95% CI 1.01-3.74, p = 0.046) was significantly higher in late-onset GDM group than that in FBG <5.1 mmol/L group. Elevated FBG was associated with overweight or obesity during pregnancy (54.9% vs. 34.9%, OR 2.27, 95% CI 1.40-3.68, p = 0.001). 6.3% of singleton pregnancies with normal GDM screening results in the first and second trimester were found to have late-onset GDM by additional FBG screening at 32-34 GW, and their risk of macrosomia during a full-term pregnancy remains significantly higher after standard treatment.

Risk of gestational diabetes in women with PCOS based on body mass index: The Japan Environment and Children's Study.

Women with polycystic ovary syndrome (PCOS), which is the most common endocrine disorder in women of reproductive age, have a potentially increased risk of gestational diabetes mellitus (GDM). To examine the impact of PCOS on GDM based on maternal body mass index (BMI) using data from a large birth cohort study in Japan. Prospective observational study using data from the Japan Environment and Children's Study (JECS). Singleton pregnancies in the JECS during 2011-2014 were included. Mothers with HbA1c levels of ≥6.5% in the first trimester and history of DM or steroid use during pregnancy were excluded. Participants were categorized according to their pre-pregnancy BMIs: G1 (<18.5 kg/m2), G2 (18.5-19.99 kg/m2), G3 (20.0-22.99 kg/m2), G4 (23.0-24.99 kg/m2), and G5 (≥25.0 kg/m2). The impact of PCOS on early (Ed) and late-onset (Ld) GDM for each group was estimated using a multiple logistic regression model. We included 92774 participants, comprising 2012 PCOS(+) cases. GDM occurrence was higher in women with PCOS (p<0.001). PCOS had no effect on GDM in G1, G2, and G3. In G4, PCOS increased the risk of Ed GDM (adjusted odds ratio [aOR]: 3.27, 95% confidence interval [CI]: 1.29-8.29). In G5, PCOS increased the risk of both Ed (aOR: 2.48, 95% CI: 1.53-4.02) and Ld GDM (aOR: 1.94, 95% CI: 1.23-3.07). The impact of PCOS on GDM occurrence depended on the pre-pregnancy BMIs, which may facilitate personalized preconception counseling among women with PCOS.

Is glucose pattern of OGTT associated with late-onset gestational diabetes and adverse pregnant outcomes?

Background The heterogeneity of oral glucose tolerance test (OGTT) patterns during pregnancy remains unclear. This study aims to identify latent OGTT patterns in pregnant women and investigate the high-risk population for late-onset gestational diabetes mellitus (GDM). Methods This study including 17,723 participants was conducted from 2018 to 2021. Latent mixture modeling was used to identify subgroups. Modified Poisson regression was performed to explore the relationship between OGTT patterns and late-onset GDM or adverse perinatal outcomes. Results Three distinct glucose patterns, high, medium, and low glucose levels (HG, MG, and LG patterns) were identified. The HG pattern represented 28.5% of the participants and 5.5% of them developed late-onset GDM. A five-fold higher risk of late-onset GDM was found in HG pattern than in LG pattern (relative risk [RR]: 5.17, 95% confidence interval [CI]: 3.38-7.92) after adjustment. Participants in HG pattern were more likely to have macrosomia, large for gestational age, preterm birth, and cesarean deliveries, with RRs of 1.59 (1.31-1.93), 1.55 (1.33-1.82), 1.30 (1.02-1.64) and 1.15 (1.08-1.23), respectively. Conclusion Three distinct OGTT patterns presented different risks of late-onset GDM and adverse perinatal outcomes, indicating that timely monitoring of glucose levels after OGTT should be performed in pregnant women with HG pattern.

Risk for fetal malformations and unfavorable neonatal outcomes in early-onset gestational diabetes mellitus.

Early-onset gestational diabetes mellitus (GDM) is diagnosed before the 24th gestational week. Since early GDM is associated with first trimester hyperglycemia, many clinicians treat these women as having pre-GDM. However, whether early GDM increases the risk for unfavorable pregnancy outcomes and particularly for fetal malformations to a greater extent than late-onset GDM were not studied sufficiently. We aimed to examine the effect of early-onset GDM on unfavorable pregnancy outcomes. A retrospective cohort study of women with GDM delivering singletons during 2005-2018 was conducted. Women were divided into GDM diagnosed at the first (Trimester1; up to 13.6weeks; N = 117), the second (Trimester2; up to 23.6weeks; N = 126), and the third trimester (Trimester3; N = 2334). The primary outcomes were neonatal malformations and a composite of large-for-age newborns, hypoglycemia and hyperbilirubinemia treated with phototherapy. Comparisons were made between early- (Trimester1 + Trimester2-groups) and late-onset GDM (Trimester3-group), and between the three trimesters. Fetal malformations were low and comparable between the trimester1, trimester2, trimester3 groups (2 (1.7%), 3 (2.4%), and 110 (4.7%), respectively).The composite neonatal complications was similar between the groups (68 (58%), 58 (46%), and 1087 (47%), respectively). In early-onset, the rates of neonatal hypoglycemia and shoulder dystocia were higher than in the late-onset GDM group (OR 95% CI 3.5 [2.0-6.1] and 10.3 [2.4-44.6], respectively). Macrosomia was higher in trimester1 compared with trimester2 and trimester3 cohorts (OR 95% CI 5.3 [1.7-16.9] and 2.8 [1.5-5.2], respectively). The risk for fetal malformations was low and comparable between the first, second and third trimester GDM. Since the risks for macrosomia, shoulder dystocia, and neonatal hypoglycemia are higher in early-onset GDM, these women should undergo strict glycemic control, intensive monitoring, and careful neonatal evaluation.

Risk factors for postpartum urinary incontinence: The impact of early-onset and late-onset Gestational Diabetes Mellitus in a nested case-control study

BackgroundGestational Diabetes Mellitus (GDM) and many other clinical variables have been associated with postpartum urinary incontinence (UI). However, the data are still restricted, and no study explored early- or late-onset GDM as a risk factor for this condition. We aimed to identify independent risk factors for postpartum UI, focusing on GDM and its early or late onset. Methods: A nested case control derived from the Diamater cohort study included 517 pregnant women who submitted to a planned C-section and followed by 6–18 months after delivery according to the timing of GDM diagnosis: early-onset GDM (before 20 weeks) and late-onset GDM(24–28 weeks) and the occurrence of UI. Results: Univariate analysis showed that the risk for 6–18 months postpartum UI was 49% higher in non-Caucasian ethnicity (1.49,1.02–2.18), 3,3 times higher in previous bariatric surgery [3.37,1.36–8.21], 39% higher in GDM women (1.39,1.01–1.93), and 5% higher for each BMI score in prepregnancy (1.05, 1.03–1.08) and at the end of pregnancy (1.05,1.02–1.08). Multivariate logistic regression analysis indicates that prepregnancy BMI was the only independent factor associated with the 6–18 months postpartum UI (adj 1.05, 95 %CI 1.02–1.08, P <.001). After stratifying, a second univariate and multivariate analysis were done according to the prepregnancy BMI cutoff score of 25. Thus, a significant association between GDM and postpartum UI in prepregnancy overweight women (RR: 1.91; 95 %CI 1.25–2.90, P =.003) and no association between GDM and 6–18 months postpartum UI in normal prepregnancy BMI (RR: 0.78, 95 %CI 0.39–1.54, P =.482) were found. After multivariate regression, the early-onset-GDM remained the unique independent adjusted risk factor for 6–18 months postpartum UI analysis (adjRR 2.15, 95 %CI 1.33–3.46, P =.002). Conclusion: After a planned C-section, we observed a 6–18 months postpartum UI higher occurrence after GDM, either in early-onset GDM or late-onset GDM. In addition, being overweight (BMI > 25) among women with early-onset GDM was associated with postpartum UI.

PM2.5 constituents and onset of gestational diabetes mellitus: Identifying susceptible exposure windows

Fine particulate matter (PM2.5) has been linked to gestational diabetes mellitus (GDM). However, PM2.5 is a complex mixture with large spatiotemporal heterogeneities, and women with early-onset GDM (i.e., diagnosed before 24th gestation week) have distinct maternal characteristics and a higher risk of worse health outcomes compared with those with late-onset GDM (i.e., diagnosed in or after 24th gestation week). We aimed to examine differential impacts of PM2.5 and its constituents on early-vs. late-onset GDM, and to identify corresponding susceptible exposure windows. We leveraged statewide linked electronic health records and birth records data in Florida in 2012–2017. Exposures to PM2.5 and its constituents (i.e., sulfate [SO42−], ammonium [NH4+], nitrate [NO3−], organic matter [OM], black carbon [BC], mineral dust [DUST], and sea-salt [SS]) were spatiotemporally linked to pregnant women based on their residential histories. Cox proportional hazards models and multinomial logistic regression were used to examine the associations of PM2.5 and its constituents with GDM and its onsets. Distributed non-linear lag models were implemented to identify susceptible exposure windows. Exposures to PM2.5, SO42−, NH4+, and BC were statistically significantly associated with higher hazards of GDM. Exposures to PM2.5 during weeks 1–12 of gestation were positively associated with GDM. Associations of early-onset GDM with PM2.5 in the 1st and 2nd trimesters, SO42− in the 1st and 2nd trimesters, and NO3− in the preconception and 1st trimester were considerably stronger than observations for late-onset GDM. Our findings suggest there are differential associations of PM2.5 and its constituents with early-vs. late-onset GDM, with different susceptible exposure windows. This study helps better understand the impacts of air pollution on GDM accounting for its physiological heterogeneity.

Early-Onset of Gestational Diabetes vs. Late-Onset: Can We Revamp Pregnancy Outcomes?

We assessed risk factors, antenatal and intrapartum complications associated with early-onset Gestational diabetes mellitus (GDM) in comparison with late-onset GDM. This retrospective study included 161 GDM women having singleton pregnancies, without previous medical disorder and delivered at a tertiary care Hospital in Ha'il City, KSA from Dec 2020 till Jun 2021. Women diagnosed at < 24 weeks of pregnancy were grouped as early-onset GDM (n=71) and those diagnosed at ≥ 24 weeks as late-onset GDM (n=90). Both groups were matched for background variables. Chi-square and binary logistic regression analysis were applied with P-value significance at 0.05. Past history of GDM, macrosomia and stillbirth were significant predictors for early-onset GDM (P value 0.000, 0.002 and 0.040 respectively). Regression analysis showed early-onset GDM significantly increases the risk for recurrent urinary tract infections (AOR 2.35), polyhydramnios (AOR 2.81), reduced fetal movements (AOR 2.13), intrauterine fetal demise (AOR 8.06), macrosomia (AOR 2.16), fetal birth trauma (2.58), low APGAR score at birth (AOR 8.06), and neonatal ICU admissions (AOR 2.65). Rate of preterm birth, hypertensive disorders, labor onset (natural vs. induced) and cesarean section and intrapartum maternal complications were same in both groups. Early-onset GDM significantly increases certain maternal (recurrent urinary tract infections, polyhydramnios and reduced fetal movements) and fetal complications (intrauterine fetal demise, macrosomia fetal birth trauma, low APGAR score at birth and neonatal ICU admissions). Most of these adverse pregnancy outcomes can be prevented through early registration and screening, close follow up, growth ultrasounds, and provision of efficient emergency and neonatal care services.

Screening for late-onset gestational diabetes: Are there any clinical benefits?

To determine whether screening for gestational diabetes mellitus (GDM) in the third trimester and managing those who are screen positive on a diabetes pathway affects obstetric and neonatal outcomes. Retrospective study of prospectively collected data. London Teaching Hospital. A total of 14 366 women delivering between 1 January 2018 and 31 December 2020. Retrospective chart analysis. Diagnosis of late-onset GDM, obstetric and neonatal outcomes. Five hundred and thirty-one women were tested by home glucose monitoring for late-onset GDM from 33 weeks of gestation. In all, 244 were diagnosed as having GDM (group 1) and managed accordingly, and 287 (group 2) were returned to normal care. A total of 1415 women had GDM diagnosed by oral glucose tolerance test before 33 weeks of gestation (group 3). Of the women in group 2, 49.5% had a spontaneous onset of labour compared with only 25.8% and 27% in groups 1 and 3. However, women in group 2 were significantly more likely to have a macrosomic baby (≥4000 g, 25.4%) than groups 1 (16.0%) or 3 (7.2%), and their babies were more likely to be admitted to special care (5.2% versus 2% in group 1). Macrosomic babies were associated with significantly higher rates of shoulder dystocia, third- and fourth-degree tears and postpartum haemorrhage. Apparent late-onset GDM affects a significant proportion of women, and targeted intervention was associated with better obstetric and neonatal outcomes. These results suggest that all pregnancies with risk factors for late-onset GDM might benefit from active GDM management irrespective of specific glucose thresholds. Women with risk factors for GDM in the third trimester, and their babies, would probably benefit from active management of their blood sugars irrespective of threshold values.

Proportion of abnormal second 50-g glucose challenge test in gestational diabetes mellitus screening using the two-step method in high-risk pregnant women.

To determine the merit of repeating 50-g glucose challenge test (50-g GCT) at 24-28 weeks of gestation in high-risk pregnant women and the prevalence of early- and late-onset gestational diabetes mellitus (GDM). This study was conducted in 1447 pregnant women, 344 of them were at risks for GDM undergoing screening by two-step method at first visit. Data were not completely collected in 47 women leaving only 297 for analyses. Fifty-six of 297 pregnant women were diagnosed as early-onset GDM (18.8%) and the other 241 pregnant women were consequently screened at 24-28 weeks of gestation to identify late-onset GDM. Screening data were retrieved, including risks, laboratory test results, baseline characteristics and diagnostic outcomes. Proportion of abnormal second 50-g GCT and the prevalence of late-onset GDM were estimated. The prevalence of late-onset GDM was 17.8%. Among groups of normal 50-g GCT, abnormal 50-g GCT and abnormal 1 oral glucose tolerance test (OGTT) value at first test, the proportions of abnormal 50-g GCT at second test were 38.3%, 59.5% and 79.3%, and the prevalence of late-onset GDM among each group were 18.8%, 8.3% and 41.4%, consecutively. This lead to prevalence of GDM in this high-risk group of 33.3% and overall among 1447 women was 7.9%. There were high proportions of abnormal 50-g GCT at second test in the groups with abnormal 50-g GCT and abnormal 1 OGTT value at first test (59.5% and 79.3%). Authors suggested doing OGTT without repeating 50-g GCT in these groups coming at 24-28 weeks of gestation.

Comparison of risk factors and pregnancy outcomes of gestational diabetes mellitus diagnosed during early and late pregnancy

ObjectiveTo compare risk factors and pregnancy outcomes of gestational diabetes mellitus (GDM) diagnosed during early and late pregnancy. DesignProspective population-based cohort study. SettingCommunity health care centers of Isfahan, Iran. Participants and measurements1000 pregnant women who were eligible and consented to participate underwent fasting plasma glucose testing at the first prenatal visit (6–14 weeks). The women free from GDM or overt diabetes were screened at 24–28 weeks of gestation using a 75-g, 2-hour oral glucose tolerance test. The diagnosis of GDM was reached through the International Association of the Diabetes and Pregnancy Study Groups. Early-onset GDM was defined as the diagnosis of GDM at the first prenatal visit. Late-onset GDM was defined as the diagnosis of GDM later at 24–28 weeks. FindingsPrevalence of GDM was 10% (95% CI: 8.1–11.9) at the first prenatal visit. GDM incidence was 9.3% (95% CI: 7.4–11.2) at 24–28 weeks of gestation. Family history of diabetes, and previous gestational diabetes and maternal age were the independent risk factors for GDM during early and late diagnosis. GDM was associated with increased risk of macrosomia, large for gestational age, and cesarean section in both periods while, neonates of women with early-onset GDM were more likely to have an apgar score at 1-min < 7, and neonatal respiratory distress syndrome and were more admitted to the neonatal intensive care unit. Key conclusion and implication for practiceDespite early screening and current practice management, early-onset GDM was associated with poorer pregnancy outcomes compared to the late-onset group. Women with early-onset GDM would benefit from more strict surveillance and management strategies to improve pregnancy outcomes. Further studies are needed to evaluate the efficacy of alternative management approaches in these high risk women.

Screening and Treatment for Early-Onset Gestational Diabetes Mellitus: a Systematic Review and Meta-analysis.

We conducted a systematic review to evaluate the current evidence for screening and treatment for early-onset gestational diabetes mellitus (GDM) RECENT FINDINGS: Many of the women with early GDM in the first trimester do not have evidence of hyperglycemia at 24-28weeks' gestation. A high proportion (15-70%) of women with GDM can be detected early in pregnancy depending on the setting, criteria used and screening strategy. However, there remains no good evidence for any of the diagnostic criteria for early-onset GDM. In a meta-analysis of 13 cohort studies, perinatal mortality (relative risk (RR) 3.58 [1.91, 6.71]), neonatal hypoglycemia (RR 1.61 [1.02, 2.55]), and insulin use (RR 1.71 [1.45, 2.03]) were greater among early-onset GDM women compared to late-onset GDM women, despite treatment. Considering the high likelihood of benefit from treatment, there is an urgent need for randomized controlled trials that investigate any benefits and possible harms of treatment of early-onset GDM.

Isolated polyhydramnios in the third trimester: is a gestational diabetes evaluation of value?*

We evaluated implications of testing for gestational diabetes mellitus (GDM) in pregnancies complicated by third trimester isolated polyhydramnios with previous negative diabetes screening test. In this retrospective cohort study of 104 pregnant women with polyhydramnios between 2005 and 2013, all had normal first trimester fasting glucose and normal glucose challenge test (GCT < 140 mg/dL). Late onset GDM was diagnosed in five women (4.8%) with isolated polyhydramnios, one abnormal value in the oral glucose tolerance test (OGTT) was identified in four additional women (3.8%). No significant differences were found in risk factors for GDM, mean second trimester GCT (117.5 vs. 107.2 mg/dL, p = 0.38) or fasting glucose values (82 vs. 86 mg/dL, p = 0.29) between women in the polyhydramnios group with and without late GDM diagnosis. Moreover, no significant difference was found in relation to the mode of delivery or birth weight between the studied groups (3437 ± 611 vs. 3331 ± 515 g, p = 0.63). Diagnosis of third trimester polyhydramnios was not associated with increased risk for GDM or neonatal complications.

Third trimester abnormal oral glucose tolerance test and adverse perinatal outcome

Objective: To compare perinatal outcome of women after third trimester oral glucose tolerance test (GTT) following normal glucose challenge test (GCT) stratified by test results.Study design: Retrospective cohort study of women delivered in a tertiary, university affiliated medical center (2007–2012). Inclusion criteria were women with a normal 50 g GCT (<140 mg/dl) followed by GTT, who delivered a live-born fetus >28 gestational weeks. Gestational diabetes mellitus (GDM) was defined as ≥2 pathological values on GTT (Carpenter and Coustan’s criteria). Perinatal outcome was stratified by GTT results: normal (if all 4 values were normal), single pathological value or GDM. Logistic regression analysis was utilized to adjust outcomes to potential confounders.Results: Overall, 323 women met inclusion criteria. Of them, 277 (85.8%) had 4 normal values, 32 (9.9%) had a single pathological value and 14 (4.3%) had late-onset GDM. Infants of mothers diagnosed and treated as GDM had lower birth weights, compared to non-diabetics and those with a single pathological value GTT. Mothers with GTT ≥1 pathological values had statistically insignificant higher rates of cesarean delivery. However, this difference was not significant after adjustment to potential confounders.Conclusion: Treatment of late-onset GDM may lead to lower birthweights, presumably due to glucose control. No association was found with cesarean delivery or neonatal outcome.

Marked decline in beta cell function during pregnancy leads to the development of glucose intolerance in Japanese women

The aim of this study is to investigate glucose metabolism longitudinally during pregnancy to explore mechanisms underlying gestational diabetes mellitus (GDM). We reviewed a total of 62 pregnant Japanese women who underwent a 75g oral glucose tolerance test (OGTT) twice during pregnancy (median: early, 13; late, 28 weeks' gestation) because of positive GDM screening. All showed normal OGTT results in early pregnancy. Based on late OGTT, 15 had GDM (late-onset GDM) and 47 normal glucose tolerance (NGT). In early pregnancy, there were no significant differences in insulin sensitivity (insulin sensitivity index derived from OGTT [IS(OGTT)] and homeostasis model assessment for insulin resistance [HOMA-IR]) and insulin secretion (a ratio of the total area-under-the-insulin-curve to the total area-under-the-glucose-curve [AUC(ins/glu)] and insulinogenic index [IGI]) between the NGT and late-onset GDM groups. In each group, insulin sensitivity significantly decreased from early to late pregnancy, most in the late-onset GDM group (each p < 0.05). The insulin secretion showed no significant changes with advancing pregnancy in both of the groups, although late-onset GDM showed significantly lower IGI compared with NGT in late OGTT (p < 0.05). When assessed beta cell function by OGTT-derived disposition index (i.e. Insulin Secretion-Sensitivity Index-2 and IGI/fasting insulin), the indices significantly decreased from early to late pregnancy in the both groups (each p < 0.05). Women with late-onset GDM showed significantly lower indices compared with NGT (each p < 0.05). The failure of beta cell to compensate for decreased insulin sensitivity could contribute to the development of the late-onset GDM.

Complex expression changes of the placental endothelin system in early and late onset preeclampsia, fetal growth restriction and gestational diabetes

AimsPreeclampsia (PE), fetal growth restriction (FGR) and gestational diabetes mellitus (GDM) are major pregnancy complications affecting maternal and fetal health. The placenta and the vasoconstrictor endothelin-1 (ET-1) have a controlling and mediating role in these conditions. This study tested the hypothesis that the expression of ET-1 and its receptors (ETA and ETB) is altered in these pathologies and differs between early (gestational week [GW]≤34) and late (GW>34) third trimester pregnancies. Main methodsThe study included 88 women (GW 28-41) with PE (blood pressure >140/90mmHg, protein >300mg/24hrs; n=14), FGR (<10th birthweight centile and pathological umbilical blood flow; n=13), PE+FGR (n=5) and GDM (n=21), and gestational age-matched controls (n=35). ET-1, ETA and ETB mRNA and ETA and ETB protein were quantified in placental tissues by real-time PCR and immunoblotting. Key findingsThe ET/ETR mRNA system is altered in PE and PE+FGR and GDM. Expression of ET-1, ETA and ETB is upregulated in early onset PE and PE+FGR with stronger effect in PE+FGR. GDM down regulated ET/ETR mRNA in the placentas in late third trimester of pregnancy. ET/ETR protein is virtually unchanged. SignificanceEarly onset PE (≤GW34) with or without FGR is associated with increased mRNA expression of the ET/ETR system, while in late onset PE and GDM the opposite effect was observed. This study supports the emerging concept that early and late onset PE are different diseases.

Cytokine profile, metabolic syndrome and cardiovascular disease risk in women with late-onset gestational diabetes mellitus

Inflammation is an important component of the metabolic syndrome (MetS) which could be the link between the metabolic and the cardiovascular consequences of this condition. Gestational diabetes mellitus (GDM) has been recognized as a significant risk factor for MetS and an inflammation component has been described in this disease. The aim of the study was to evaluate the relationships between cytokine concentrations, components of MetS and cardiovascular risk markers in women with late-onset GDM. Women (n=63) with late-onset GDM and 63 controls were enrolled. Clinical variables, and obstetrics and perinatal outcomes were recorded. Relationships between cytokines (TNF-α, leptin, IL6, adiponectin) and endothelial injury markers (VCAM, ICAM and selectine) were analyzed. Control vs. patient data indicated: pre-gestational body mass index (BMI) 23.46±3.73 vs. 26.97±5.07kg/m2 (p=0.001); TNF-α 2.2±0.8 vs. 3.1±1.5pg/mL (p=0.002); leptin 18714.78±8859.08 vs. 27365.79±16209.67pg/mL (p=0.001); adiponectin 162.42±34.19 vs. 141.54±41.33ng/mL (p=0.04). Multivariate analyses showed that adiponectin had a protective effect (OR=0.9; p=0.02) and BMI carried a significant risk (OR=8.4; p=0.01) for GDM. No differences were found in endothelial injury markers. In conclusion, the cytokine profile in women with late-onset GDM is characterized by high concentrations of TNF-α and leptin and low adiponectin. This profile is related, in large extent, to an increased pregravid BMI which, potentially, may be linked to the future development of both metabolic and cardiovascular disease.

Gestational diabetes mellitus (GDM) screening in morbidly obese pregnant women

ObjectiveTo study the outcomes of two-stage GDM screening of morbidly obese women in our obstetric unit and to evaluate the diagnostic performance of 20-week oral glucose tolerance test (OGTT) values in predicting or excluding late onset GDM. Study designA retrospective study in which 190 pregnant women with BMI ≥40 had two-stage screening: a 75g OGTT is performed at 20 weeks and repeated at 28 weeks if the 20-week OGTT was normal. Receiver operating characteristic (ROC) curves for 20-week OGTT values were constructed in order to obtain an optimal cut-off value of fasting and/or 2-h glucose at 20 weeks from which GDM could be predicted or excluded at 28 weeks. Sensitivity, specificity, positive likelihood ratio, and negative likelihood ratio were determined for each of the fasting and 2-h post-load glucose values at 20 weeks. ResultsForty six (24%) women were diagnosed with GDM. Thirty-two (70%) were diagnosed at 20 weeks and 14 (30%) at 28 weeks. The 2-h cut-off value of ≥6mmol/l at the 20-week OGTT had a negative likelihood ratio of 0.12 to predict GDM at 28 weeks. The low negative likelihood ratio reduces the probability of detecting GDM at 28 weeks from 9% (pre-test probability) to 1% (post-test probability). ConclusionNearly 70% of the women were diagnosed with GDM at 20 weeks, which gives an early opportunity to treat maternal hyperglycaemia with consequent health benefits. A 2-h cut-off glucose value of 6mmol/l at 20 weeks OGTT has a low negative likelihood ratio which virtually excludes GDM at 28 weeks. Hence women with a 2h value of <6mmol/l at 20 weeks can avoid a repeat 28 week OGTT test.

Oxidative stress and antioxidant status in patients with late-onset gestational diabetes mellitus

The relationship between late-onset gestational diabetes mellitus [GDM] and oxidative stress is not well known, and the importance of the oxidant/antioxidant equilibrium in the clinical evolution and its complications require elucidation. The aim of the study was to evaluate the relationships between maternal levels of markers of oxidative stress in women with late-onset GDM that, potentially, may have considerable clinical implications in the pathogenesis and/or the evolution of GDM. Pregnant women (n=78; 53 with GDM, 25 controls), between the 24th and 29th week of gestation, were enrolled. Both groups were analysed for demographic data, perinatal and obstetrics outcomes together with the levels of the marker's oxidative stress and antioxidant status. Control versus patient results in the univariate analysis were the following: pre-gestational body mass index [BMI] 23.31±4.2 vs. 27.13±4.6kg/m(2) (P=0.001); weeks at delivery 39.2±3.05 vs. 38.9±1.8 (P=0.09); Caesarean delivery 12.5 vs. 43% (P=0.004); macrosomia 4 vs. 9.4% (P=0.6); lipoperoxides [LPO] 2.06±1.00 vs. 3.14±1.55μmol/mg (P=0.001); catalase 3.23±1.41 vs. 2.52±1.3nmol/min/ml (P=0.03); superoxide dismutase [SOD] 0.11±0.04 vs. 0.08±0.01U/ml (P=0.0003); glutathione peroxidase [GPX] 0.03±0.006 vs. 0.025±0.006nmol/min/ml (P=0.01); glutathione reductase [GSH] 0.004±0.002 vs. 0.004±0.004nmol/min/ml (P=0.9)]; and glutathione transferase [GST] 0.0025±0.0012 vs. 0.0027±0.00017nmol/min/ml (P=0.7). Multivariate analysis showed catalase might have a protective effect against GDM development and LPO seems to be a risk factor for the disease. These data suggest an increase in oxidative stress and a decrease in antioxidative defence in women with late-onset GDM and, as such, may have considerable clinical implications in the pathogenesis and/or the course of the pregnancy in these patients.