Late Gestational Diabetes Mellitus Research Articles

Use of the Japanese gestational diabetes mellitus diagnostic strategy during the COVID‐19 pandemic in Japan: A questionnaire survey

AbstractAimSome concerns exist that diagnosis of gestational diabetes mellitus (GDM) may be missed when the simplified diagnostic criteria of the Japanese Society of Diabetes and Pregnancy (JSDP) for GDM (published during the COVID‐19 pandemic) are used. Moreover, limited data is available regarding how widespread these diagnostic criteria are used when managing GDM during the COVID‐19 pandemic. Therefore, this study aimed to determine how GDM diagnosis has changed during the COVID‐19 pandemic in Japan.MethodsThe changes in GDM diagnosis during the COVID‐19 pandemic were investigated using an online questionnaire to 2159 obstetric facilities in Japan. The questionnaire collected data on facility type, awareness of Japanese GDM diagnostic strategies, modifications to diagnostic methods for early and late GDM, and opinions on GDM management, with the pandemic divided into seven periods.ResultsWe received responses from 593 facilities (27%). Approximately 90% of the facilities did not change their diagnostic process for early GDM or late GDM (occurring after 24 weeks gestation). However, during the COVID‐19 pandemic, 19 facilities discontinued the use of 75‐g oral glucose tolerance tests before 24 weeks of gestation, and 17 facilities discontinued it after 24 weeks of gestation, instead using the aforementioned Japanese GDM diagnostic strategy.ConclusionsAlthough a limited number of facilities modified their diagnostic method in response to the COVID‐19 pandemic, this study demonstrated that those that adjusted their diagnostic method primarily used the Japanese COVID‐19 GDM strategy by the JSDP.

Perinatal Outcomes in Early and Late Gestational Diabetes Mellitus After Treatment From 24-28 Weeks' Gestation: A TOBOGM Secondary Analysis.

In most gestational diabetes mellitus (GDM) studies, cohorts have included women combined into study populations without regard to whether hyperglycemia was present earlier in pregnancy. In this study we sought to compare perinatal outcomes between groups: women with early GDM (EGDM group: diagnosis before 20 weeks but no treatment until 24-28 weeks if GDM still present), with late GDM (LGDM group: present only at 24-28 weeks), and with normoglycemia at 24-28 weeks (control subjects). This is a secondary analysis of a randomized controlled treatment trial where we studied, among women with risk factors, early (<20 weeks' gestation) GDM defined according to World Health Organization 2013 criteria. Those receiving early treatment for GDM treatment were excluded. GDM was treated if present at 24-28 weeks. The primary outcome was a composite of birth before 37 weeks' gestation, birth weight ≥4,500 g, birth trauma, neonatal respiratory distress, phototherapy, stillbirth/neonatal death, and shoulder dystocia. Comparisons included adjustment for age, ethnicity, BMI, site, smoking, primigravity, and education. Women with EGDM (n = 254) and LGDM (n = 467) had shorter pregnancy duration than control subjects (n = 2,339). BMI was lowest with LGDM. The composite was increased with EGDM (odds ratio [OR] 1.59, 95% CI 1.18-2.12)) but not LGDM (OR 1.19, 95% CI 0.94-1.50). Induction of labor was higher in both GDM groups. In comparisons with control subjects there were higher birth centile, higher preterm birth rate, and higher rate of neonatal jaundice for the EGDM group (but not the LGDM group). The greatest need for insulin and/or metformin was with EGDM. Adverse perinatal outcomes were increased with EGDM despite treatment from 24-28 weeks' gestation, suggesting the need to initiate treatment early, and more aggressively, to reduce the effects of exposure to the more severe maternal hyperglycemia from early pregnancy.

Maternal birth weight as an indicator of early and late gestational diabetes mellitus: The Japan Environment and Children's Study.

This study aimed to investigate the association of maternal birth weight (MBW) with early and late gestational diabetes mellitus (GDM). A total of 69318 pregnant Japanese women were included in this birth cohort study. The associations between maternal birth weight and early gestational diabetes mellitus (diagnosed at <24 gestational weeks) and late GDM (diagnosed at ≥24 gestational weeks) were investigated using a multinomial logistic regression model, with an maternal birth weight of 3000-3499 g as the reference category. Lower maternal birth weight was associated with higher odds of developing early and late gestational diabetes mellitus (P < 0.0001 and P < 0.0001, respectively). The adjusted odds ratios (aORs) for early gestational diabetes mellitus in participants with a MBW of <2500 g and 2500-2999 g were 1.345 (95% confidence interval [CI]: 0.912-1.984) and 1.338 (95% CI: 1.098-1.629), respectively. The aORs for late gestational diabetes mellitus in participants with a MBW of <2500 g and 2500-2999 g were, 1.657 (95% CI: 1.298-2.115) and 1.218 (95% CI: 1.058-1.402), respectively. Regardless of the gestational age when gestational diabetes mellitus was diagnosed, a lower maternal birth weight was associated with an increased risk of gestational diabetes mellitus. Furthermore, the association of a MBW <2500 g with late gestational diabetes mellitus tended to be stronger than that with early gestational diabetes mellitus.

The impact on pregnancy outcomes of late-onset gestational diabetes mellitus diagnosed during the third trimester: A systematic review and meta-analysis.

Evidence is inconsistent regarding the impact of late gestational diabetes mellitus (GDM) on perinatal outcomes. To evaluate associations of GDM diagnosed in the third trimester (late GDM) with adverse obstetric and neonatal outcomes. We searched Embase, Medline, and Web of Science from January 1, 1990 to June 16, 2022, for observational studies. Late GDM was defined as a de novo diagnosis, i.e. after a negative screening for diabetes in the second trimester, and at later than 28 weeks of pregnancy. Each abstract and full-text article was independently reviewed by the same two authors. Quality was assessed with the use of the Newcastle-Ottawa Scale. Summary odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using a random effects model. Twelve studies were identified as meeting the inclusion criteria, including 3103 patients (571 with late GDM and 3103 controls). Incidences of shoulder dystocia (OR 1.57, 95% CI 1.02-2.42, P = 0.040), 5-minute Apgar score <7 (OR 1.80, 95% CI 1.14-2.86, P = 0.024), cesarean delivery (OR 1.98, 95% CI 1.51-2.60, P < 0.001), and emergent cesarean delivery (OR 1.57, 95% CI 1.02-2.40, P = 0.040) were significantly higher among women with late GDM than among the controls. The groups showed similarity in the rates of fetal macrosomia, large-for-gestational-age fetuses, neonatal hypoglycemia, and hypertensive disorders of pregnancy. This meta-analysis showed associations of late GDM with increased adverse perinatal outcomes. Prospective studies should evaluate the impact on perinatal outcomes of repeated third-trimester screening for late GDM.

STZ-induced gestational diabetes exposure alters PTEN/AKT/mTOR-mediated autophagy signaling pathway leading to increase the risk of neonatal hypoxic-ischemic encephalopathy

Exposure to gestational diabetes mellitus (GDM) during pregnancy has significant consequences for the unborn baby and newborn infant. However, whether and how GDM exposure induces the development of neonatal brain hypoxia/ischemia-sensitive phenotype and the underlying molecular mechanisms remain unclear. In this study, we used a late GDM rat model induced by administration of streptozotocin (STZ) on gestational day 12 and investigated its effects of GDM on neonatal brain development. The pregnant rats exhibited increased blood glucose levels in a dose-dependent manner after STZ administration. STZ-induced maternal hyperglycemia led to reduced blood glucose levels in neonatal offspring, resulting in growth restriction and an increased brain to body weight ratio. Importantly, GDM exposure increased susceptibility to hypoxia/ischemia (HI)-induced brain infarct sizes compared to the controls in both male and female neonatal offspring. Further molecular analysis revealed alterations in the PTEN/AKT/mTOR/autophagy signaling pathway in neonatal male offspring brains, along with increased ROS production and autophagy-related proteins (Atg5 and LC3-II). Treatment with the PTEN inhibitor bisperoxovanadate (BPV) eliminated the differences in HI-induced brain infarct sizes between the GDM-exposed and the control groups. These findings provide novel evidence of the development of a brain hypoxia/ischemia-sensitive phenotype in response to GDM exposure and highlight the role of the PTEN/AKT/mTOR/autophagy signaling pathway in this process.

Serum selenium, selenoprotein P, and glutathione peroxidase 3 during early and late pregnancy in association with gestational diabetes mellitus: Prospective Odense Child Cohort

BackgroundDiet is an important modifiable risk factor for gestational diabetes mellitus (GDM) and its related complications; however, the role of essential micronutrients such as selenium (Se), particularly in populations with low Se intake, is inconclusive. ObjectivesThe aim was to investigate the association of 3 established biomarkers of Se status with GDM, gestational glucose metabolism, and large for gestational-age offspring. MethodsThis study included 1346 pregnant females with 2294 serum samples from the prospective, population-based Odense Child Cohort study, Denmark. Serum Se, selenoprotein P (SELENOP) concentrations, and glutathione peroxidase 3 (GPX3) activity were measured in early and late pregnancy, and fasting glucose and insulin assessments in late pregnancy. Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) was calculated, and the GDM definition was according to the WHO 2013 threshold of fasting venous plasma glucose of ≥5.1 mmol/L. A subcohort underwent an oral glucose tolerance test. Regression models adjusted for various confounders quantified dose-dependent associations. ResultsSe and SELENOP declined during pregnancy. There were dose-dependent inverse associations of early GPX3 with late pregnancy GDM (WHO 2013), fasting glucose, insulin, HOMA-IR, and 2 h glucose. The odds ratio (OR) of GDM was 0.33 (95% CI: 0.16, 0.65) for 1 log-scale-increment in early GPX3 activity. Late pregnancy GPX3 and SELENOP were inversely associated with GDM and HOMA-IR; the OR of GDM was 0.21 (95% CI: 0.12, 0.38) and 0.52 (95% CI: 0.35, 0.77), for 1 log-scale-increment of GPX3 and SELENOP, respectively. A decline in Se biomarkers during pregnancy was associated with a higher risk of GDM and higher HOMA-IR. Low GPX3 activity in late pregnancy was associated with a higher risk of large for gestational-age offspring, partly (∼20%) mediated by fasting glucose concentrations (P = 0.006). ConclusionsLow serum Se in pregnancy, particularly GPX3 activity, is independently associated with risk of GDM and large for gestational age. Offering Se status assessment in pregnancy identifies females at high risk for GDM who may benefit from Se substitution.

Patients with gestational diabetes mellitus may be treated in both early and late pregnancy, especially in patients with pre-pregnancy overweight: A cross-sectional study in Japan.

The significance of diagnosing gestational diabetes mellitus (GDM) in early pregnancy is controversial. We used the International Association of Diabetes and Pregnancy Study Group (IADPSG) criteria to investigate whether clinical background and neonatal outcomes differ depending on when GDM is diagnosed in early or late pregnancy. This was a single-center, observational study conducted between November 2012 and March 2020 at St. Marianna University Hospital (Kawasaki, Japan). We compared the background and perinatal outcomes of patients with GDM depending on the time of diagnosis (at < 24 gestational weeks or ≥ 24weeks). Insulin sensitivity index, homeostasis model assessment of insulin resistance, and β-cell function were calculated from a 75-g oral glucose tolerance test. Stratified analysis was performed by pre-pregnancy BMI in patients with early GDM. As a result, in the 507 patients, 89.9% gave birth at our hospital. The pre-pregnancy BMI was significantly higher in patients with early GDM than in those with late GDM (the median [interquartile range], 22.7 [20.3, 26.3] and 21.5 [19.3, 23.8] kg/m2, respectively; p = 0.001). Perinatal outcomes were not different between the two groups. However, in the subgroup analysis of patients with early GDM, the prevalence of large-for-gestational-age infants was significantly higher in the group with overweight (15.4% vs 2.1%, respectively; p = 0.008). In conclusion, patients with GDM using the IADPSG criteria in early pregnancy may be treated, especially in patients with pre-pregnancy overweight.

Circulating microRNAs associated with gestational diabetes mellitus: useful biomarkers?

Different types of small non-coding RNAs, especially miRNAs, may be found in the circulation, either protein-bound or enclosed in extracellular vesicles. During gestation, and particularly during gestational diabetes mellitus (GDM), the levels of several miRNAs are altered. Worldwide the incidence of GDM is increasing, in part driven by the current obesity epidemic. This is a point of public health concern because offspring of women with GDM frequently suffer from short- and long-term complications of maternal GDM. This has prompted the investigation of whether levels of specific miRNA species, detected early in gestation, may be used as diagnostic or prognostic markers for the development of GDM. Here, we summarize the mechanisms of RNA secretion and review circulating miRNAs associated with GDM. Several miRNAs are associated with GDM: miR-29a-3p and miR-29b-3p are generally upregulated in GDM pregnancies, also when measured prior to the development of GDM, while miR-16-5p is consistently upregulated in GDM pregnancies, especially in late gestation. miR-330-3p in circulation is increased in late gestation GDM women, especially in those with poor insulin secretion. miR-17-5p, miR-19a/b-3p, miR-223-3p, miR-155-5p, miR-125-a/b-5p, miR-210-3p and miR-132 are also associated with GDM, but less so and with more contradictory results reported. There could be a publication bias as miRNAs identified early are investigated the most, suggesting that it is likely that additional, more recently detected miRNAs could also be associated with GDM. Thus, circulating miRNAs show potential as biomarkers of GDM diagnosis or prognosis, especially multiple miRNAs containing prediction algorithms show promise, but further studies are needed.

Third trimester re-screening for gestational diabetes in morbidly obese women despite earlier negative test can reveal risks for obstetrical complications.

We investigated associations of maternal obesity with late gestational diabetes mellitus (GDM) diagnosis (>34 weeks) in women with previous normal glucose screening, and associations of late GDM with obstetrical outcomes. This retrospective cohort study assessed obstetrical and neonatal outcomes of 238 women with normal (24-28 week) glucose screening results, who underwent late repeat oral glucose tolerance tests (OGTT) (>34 weeks) due to a suspected LGA fetus (54.6%) or polyhydramnios (45.4%). A sub-analysis was performed of outcomes of women with late versus mid-trimester GDM. The GDM rate in repeat OGTT screening was 22.2% for the total sample, and 33% among women with morbid obesity. Among women with late GDM versus without late GDM, rates were higher for macrosomia, large-for-gestational-age fetus induction of labor, neonatal hypoglycemia, jaundice, and the need for phototherapy. Among women with late GDM, a higher pregestational BMI was associated with adverse maternal and perinatal outcomes. Higher risks for macrosomia and CS due to macrosomia were demonstrated in women with late vs. mid-trimester GDM. Late screening in pregnancy may reveal GDM among women with previous normal glucose screening, particularly among those with late third trimester BMI ≥ 35 kg/m2 , GDM in a previous pregnancy or fasting glucose >95 mg/dl. Women diagnosed with GDM at >34 weeks following normal glucose screening at 24-28 weeks are at higher risk for adverse perinatal outcomes. For women with morbid obesity, or suspected macrosomia or polyhydramnios in the late third trimester, and normal glucose screening in the second trimester, retesting should be considered.

Early vs. Late Gestational Diabetes: Comparison between Two Groups Diagnosed by Abnormal Initial Fasting Plasma Glucose or Mid-Pregnancy Oral Glucose Tolerance Test.

Gestational diabetes mellitus (GDM) is one of the most common complications in pregnancy. It may be diagnosed using a fasting plasma glucose (FPG) early in pregnancy (eGDM) or a 75-g oral glucose tolerance test (OGTT) (late GDM). This retrospective cohort of women with GDM presents data from 1891 patients (1004 in the eGDM and 887 in the late GDM group). Student's t-test, chi-squared or Fisher's exact test and the Bonferroni test for post hoc analysis were used to compare the groups. Women with eGDM had higher pre-pregnancy BMI, more frequent family history of DM, more frequent history of previous GDM, and were more likely to have chronic hypertension. They were more likely to deliver by cesarean section and to present an abnormal puerperal OGTT. Even though they received earlier treatment and required insulin more frequently, there was no difference in neonatal outcomes. Diagnosing and treating GDM is necessary to reduce complications and adverse outcomes, but it is still a challenge. We believe that women with eGDM should be treated and closely monitored, even though this may increase healthcare-related costs.

Clinical implications of the 100-g oral glucose tolerance test in the third trimester.

The clinical implications of gestational diabetes mellitus (GDM) diagnosed in the third trimester are not well established and controversy continues regarding the performance of diagnostic tests beyond 28-week gestation. This study aimed to evaluate the incidence of abnormal third trimester oral glucose tolerance test (OGTT) results in women at high risk and to compare the obstetric and neonatal outcomes with those of women with normal OGTT results. The study included 372 women who completed late (>29weeks) 100-g OGTT due to suspected fetal macrosomia, polyhydramnios or a personal risk factor for GDM, diagnosed according to the Carpenter & Coustan criteria. Women withonly one abnormal OGTT value were diagnosed with GDM by abnormal glucose follow-up and analyzed separately. Obstetric and neonatal outcomes were compared between the GDM and the non-GDM groups. GDM was diagnosed in 85/372 (22%) women, including 35 (59.3%) women with one abnormal OGTT value who were later diagnosed with GDM. Of 200 women who had a normal 1-h 50-g glucose challenge test at 24-28weeks, late GDM was diagnosed in 33 (16.5%). Seventy-six (89.5%) of those with GDM were treated by dietary therapy and 9 (10.5%) by pharmacological therapy. Among women with GDM, large-for-gestational-age fetuses, labor induction and elective cesarean section were more prevalent than for those without GDM. Significant differences were not found between the groups in macrosomia and neonatal outcomes. The performance of OGTT in women with risk factors during the third trimester should be considered following further prospective trials.

DNA methylation analysis of cord blood samples in neonates born to gestational diabetes mothers diagnosed before 24 gestational weeks

IntroductionGenome-wide methylation analyses of gestational diabetes mellitus (GDM) diagnosed after 24 gestational weeks (late GDM (L-GDM)) using cord blood have been reported. However, epigenetic changes in neonates born to mothers...

Mitochondrial Transfer Improves Cardiomyocyte Bioenergetics and Viability in Male Rats Exposed to Pregestational Diabetes.

Offspring born to diabetic or obese mothers have a higher lifetime risk of heart disease. Previously, we found that rat offspring exposed to late-gestational diabetes mellitus (LGDM) and maternal high-fat (HF) diet develop mitochondrial dysfunction, impaired cardiomyocyte bioenergetics, and cardiac dysfunction at birth and again during aging. Here, we compared echocardiography, cardiomyocyte bioenergetics, oxidative damage, and mitochondria-mediated cell death among control, pregestational diabetes mellitus (PGDM)-exposed, HF-diet-exposed, and combination-exposed newborn offspring. We hypothesized that PGDM exposure, similar to LGDM, causes mitochondrial dysfunction to play a central, pathogenic role in neonatal cardiomyopathy. We found that PGDM-exposed offspring, similar to LGDM-exposed offspring, have cardiac dysfunction at birth, but their isolated cardiomyocytes have seemingly less bioenergetics impairment. This finding was due to confounding by impaired viability related to poorer ATP generation, more lipid peroxidation, and faster apoptosis under metabolic stress. To mechanistically isolate and test the role of mitochondria, we transferred mitochondria from normal rat myocardium to control and exposed neonatal rat cardiomyocytes. As expected, transfer provides a respiratory boost to cardiomyocytes from all groups. They also reduce apoptosis in PGDM-exposed males, but not in females. Findings highlight sex-specific differences in mitochondria-mediated mechanisms of developmentally programmed heart disease and underscore potential caveats of therapeutic mitochondrial transfer.

Predictors of later insulin therapy for gestational diabetes diagnosed in early pregnancy.

Interventions for gestational diabetes mellitus (GDM), diagnosed in early pregnancy, have been a topic of controversy. This study aimed to elucidate factors that predict patients with GDM diagnosed before 24 gestational weeks (early GDM: E-GDM) who require insulin therapy later during pregnancy. Furthermore, we identified patients whose impaired glucose tolerance should be strictly controlled from early gestation onward. Women diagnosed with GDM were categorized based on the gestational age at diagnosis into E-GDM (n = 388) or late GDM (L-GDM, diagnosed after 24 weeks, n = 340) groups. Clinical features were compared between the groups, and the predictors for insulin therapy was evaluated in the E-GDM group. There were no significant between-group differences in terms of perinatal outcomes (e.g., gestational weeks at delivery, fetal growth, hypertensive disorder of pregnancy), with the exception of the Apgar score at 5 min. Moreover, there was no significant difference in the frequency of insulin therapy during pregnancy between the two groups. Using multiple logistic regression analysis, pre-pregnancy body mass index (BMI) ≥25 kg/m2, a family history of diabetes, and higher fasting plasma glucose (FPG), 1 h-plasma glucose (PG), and 2 h-PG values increased insulin therapy risk during pregnancy in the E-GDM group. Furthermore, since E-GDM patients with abnormal levels of FPG, as well as 1 h-PG or 2 h-PG, and those with pre-pregnancy BMI ≥25 kg/m2 and a family history of diabetes had a higher risk of later insulin therapy during pregnancy, they may require more careful follow-up in the perinatal period.

Differences in Newborn Screening Results Among Women with Gestational Diabetes Mellitus

Multiple studies undertaken on cord blood demonstrate analyte perturbations in infants exposed to gestational diabetes mellitus (GDM). Cord blood as a sample is influenced by maternal and placental metabolism. Newborn screening (NBS), performed after the first 24 hours of life reflects early neonatal metabolism. We compared NBS analytes between women with and without GDM with different management approaches in the Treatment of Booking of Gestational Diabetes (TOBOGM) pilot randomised controlled trial. Pregnant women with GDM risk factors were randomised to early or deferred GDM treatment following an oral glucose tolerance test (<20 weeks gestation). Women without GDM served as “decoys”. From the decoy group 11 developed GDM (screened at 26-28 weeks), were analysed separately; their results were compared with the other groups. De-identified controls were chosen from NBS results from the same analytic run matched for sex, birthweight and gestational age. Results were available for 73/78 women participating in the pilot and 358 de-identified controls. Tyrosine levels (μmol/l; whole blood)were higher in the late GDM group vs early, deferred treatment, and decoy groups (medians:106.28; IQR: 96.73-151.11) (76.33; 64.64-97.90) (75.68; 66.59-110.88)(73.74; 58.32-90.36) (p=0.009) and remained elevated when compared to normal, age-matched controls (106.28; 96.73-151.11) (87.26; 68.55-111.26) (p value=0.01) Immunoreactive trypsinogen (μgm/l; whole blood)was highest in the early treatment group when compared with group-specific controls (22.30; 13.90-29.90 vs 14.00, 10.60-21.10) (p=0.02). These results provide evidence of biochemical perturbations detectable on NBS of in-utero exposure to hyperglycemia and treatment and provide data for hypothesis building.

Pregnancy outcomes among multi-ethnic women with different degrees of hyperglycaemia during pregnancy in an urban New Zealand population and their association with postnatal HbA1c uptake.

Adverse pregnancy outcomes are more common in women with hyperglycaemia. Many women have suboptimal uptake of HbA1c testing postdelivery. To compare pregnancy outcomes among multi-ethnic women with different degrees of hyperglycaemia during pregnancy, and their association with postnatal HbA1c uptake after the introduction of email reminders. A retrospective and prospective single-centre study was conducted in South Auckland in 2639 women with early gestational diabetes mellitus (GDM) (diagnosed<20weeks), late GDM (diagnosed≥20weeks), overt diabetes in pregnancy, or known type 2 diabetes (T2DM) during pregnancy. Automated email reminders were sent to general practitioners to increase postnatal HbA1c screening. HbA1c during pregnancy increased across the late GDM (n=1425), early GDM (n=148), overt diabetes (n=573) and T2DM (n=493) groups (P<0.001). Stillbirth was least common in the late GDM group (0, 0.7, 0.5, and 1.9%, respectively, P<0.001), as were caesarean delivery (32.7, 45.1, 39.4, and 53.5%, respectively, P<0.001), large for gestational age (LGA) (14.7, 18.2, 22.3, and 30.5%, respectively, P<0.001), small for gestational age (8.8, 16.7, 11.0, and 11.1%, respectively, P=0.02), and preeclampsia/eclampsia (7.7, 9.2, 13.0, and 14.8%, respectively, P<0.001). LGA and preeclampsia/eclampsia were more common among Pacific and Māori women than European women (LGA, 30.1, 22.7, 10.3%, respectively, P<0.001; preeclampsia/eclampsia, 13.5, 14.0, and 8.1%, respectively, P<0.001). Postpartum HbA1c screening increased among women with GDM/overt diabetes after the introduction of the reminder emails (39.6% vs 34.0%, P=0.03). Women with late GDM are least likely to experience adverse outcomes. Email reminders to improve postpartum HbA1c screening warrant further investigation.

1385-P: Utility of Hemoglobin A1c for Predicting Adverse Pregnancy Outcomes in Women with Gestational Diabetes Mellitus

Aims: Despite current treatment strategies, gestational diabetes mellitus (GDM) remains a major risk factor for pregnancy complications. We examined whether the HbA1c measured at the time of oral glucose tolerance test (OGTT) predicts residual risk of adverse outcomes in women with treated GDM. Methods: Women with GDM (defined using the New Zealand criteria) enrolled in the Diabetes in Pregnancy Registry in South Auckland, New Zealand at ≥ 20 weeks gestation were included. Glycaemic targets used were fasting ≤5.0 mmol/l and 2-hour post-meal ≤6.7 mmol/l. Results: Of the 1403 women enrolled, 304 (21.7%) had an HbA1c 41-49 mmol/mol (5.9-6.6%). Women with higher HbA1c were significantly older, with higher BMI and fasting and 2-hour OGTT values. They were more likely to be multiparous, of Pacific ethnicity, and have a family history of diabetes. After adjusting for known risk factors, higher HbA1c was associated with increased risk of large for gestational age (LGA) babies (odds ratio (OR) 2.08 (1.47-2.93)) and preeclampsia (OR 2.09 (1.34-3.29)). The OGTT fasting glucose was predictive of LGA (OR 1.61 (1.17-2.21)), but not the 2-hour value (OR 1.12 (0.98-1.28)). The areas under the receiver operating characteristic curves for predicting LGA and preeclampsia by HbA1c, OGTT fasting, OGTT 2-hour, and 1-hour 50g polycose test were: LGA, 0.58 (0.51-0.65), 0.66 (0.59-0.73), 0.45 (0.37-0.52), and 0.59 (0.51-0.66) respectively; preeclampsia, 0.66 (0.57-0.75), 0.58(0.48-0.67), 0.46 (0.35-0.56), and 0.52 (0.42-0.62) respectively. Conclusions: HbA1c, fasting, and 1-hour glucose at GDM diagnosis predict residual adverse outcomes in treated women with late GDM. Studies are needed to test whether earlier treatment, or targeting the 1-hour post-prandial glucose can reduce this residual risk. Disclosure D. Simmons: None. J. Immanuel: None. C. Eagleton: None. J. Baker: None.

The Effect of Prior Gestational Diabetes on the Shape of the Glucose Response Curve during an Oral Glucose Tolerance Test 3 Years after Delivery.

Objective Monophasic glucose response (MGR) during an oral glucose tolerance test (OGTT) and gestational diabetes mellitus (GDM) are predictors of type 2 diabetes mellitus (T2DM). We investigated the association between current MGR and (1) glucose tolerance during a pregnancy 3 years before and (2) current glucose tolerance status. We also sought (3) other determinants of MGR. Research Design and Methods. We conducted a nested case-control study of GDM (n = 47 early GDM, diagnosed between 16 and 20 weeks of gestation; n = 40 late GDM, diagnosed between 24 and 28 weeks of gestation) and matched healthy controls (n = 37, normal glucose tolerance during pregnancy) all free from diabetes at follow-up 3.4 ± 0.6 years after delivery. Glucose tolerance was determined by 2-hour 75 g OGTT. Monophasic and biphasic groups were defined based on serum glucose measurements during OGTT. Results The biphasic group was younger, had lower triglyceride levels and area under the OGTT glucose curve, and was less frequently diagnosed with early GDM (25 vs. 45%, all p < 0.05). Women with a biphasic response also tended to have lower systolic blood pressure (p < 0.1). No differences were found in fasting and 2-hour glucose and insulin levels, or BMI. According to multiple logistic regression, MGR was associated with prior early GDM (OR 2.14, 95% CI 0.92-4.99) and elevated triglyceride levels (OR 2.28, 95% CI 1.03-5.03/log (mmol/l)). Conclusions We found that more severe, early-onset GDM was an independent predictor of monophasic glucose response suggesting that monophasic response may represent an intermediate state between GDM and manifest type 2 diabetes.

Early Pregnancy Screening for Women at High-Risk of GDM Results in Reduced Neonatal Morbidity and Similar Maternal Outcomes to Routine Screening.

The Australasian Diabetes in Pregnancy Society recommends screening high-risk women for gestational diabetes mellitus (GDM) before 24 weeks gestation, under the assumption that an earlier diagnosis and opportunity to achieve normoglycemia will minimize adverse outcomes. However, little evidence exists for this recommendation. The study objective was to compare the pregnancy outcomes of high-risk women diagnosed with GDM before 24 weeks gestation and routinely diagnosed women after 24 weeks gestation. A retrospective audit was conducted of all pregnancies diagnosed with GDM using International Association of Diabetes and Pregnancy Study Groups criteria over 12 months at a tertiary Australian hospital. Adverse perinatal outcomes were compared between “Early GDM” diagnosed before 24 weeks (n = 133) and “Late GDM” diagnosed from 24 weeks (n = 636). Early GDM had a significantly lower newborn composite outcome frequency (hypoglycemia, birth trauma, NICU/SCN admission, stillbirth, neonatal death, respiratory distress, and phototherapy) compared to Late GDM (20.3% vs. 30.0%, p = 0.02). Primary cesarean, hypertensive disorders, postpartum hemorrhage, birthweight >90th percentile, macrosomia, and preterm birth frequencies were not significantly different between groups. Therefore, high-risk women diagnosed with GDM in early pregnancy were not more likely to have an adverse outcome compared to routinely diagnosed women. As they are a high-risk group, this may indicate a possible benefit to the early diagnosis of GDM.

Skin Autofluorescence of Pregnant Women With Diabetes Predicts the Macrosomia of Their Children.

Advanced glycation end products (AGEs) accumulated during long-term hyperglycemia are involved in diabetes complications and can be estimated by skin autofluorescence (sAF). During pregnancy, hyperglycemia exposes women to the risk of having a macrosomic newborn. The aim of this study was to determine whether sAF of women with diabetes during a singleton pregnancy could predict macrosomia in their newborns. Using an AGE Reader, we measured the sAF at the first visit of 343 women who were referred to our diabetology department during years 2011-2015. Thirty-nine women had pregestational diabetes, 95 early gestational diabetes mellitus (GDM), and 209 late GDM. Macrosomia was defined as birth weight ≥4,000 g and/or large for gestational age ≥90th percentile. Forty-six newborns were macrosomic. Their mothers had 11% higher sAF compared with other mothers: 2.03 ± 0.30 arbitrary units (AUs) vs. 1.80 ± 0.34 (P < 0.0001). Using multivariate logistic regression, the relation between sAF and macrosomia was significant (odds ratio 4.13 for 1-AU increase of sAF [95% CI 1.46-11.71]) after adjusting for several potential confounders. This relation remained significant after further adjustment for HbA1c (among 263 women with available HbA1c) and for women with GDM only. sAF of pregnant women with diabetes, a marker of long-term hyperglycemic exposure, predicts macrosomia in their newborns.