GDM Women Research Articles

Gestational Diabetes Mellitus Is Associated with Reduced Dynamics of Gut Microbiota during the First Half of Pregnancy

Women with gestational diabetes mellitus (GDM) have different gut microbiota in late pregnancy compared to women without GDM. It remains unclear whether alterations of gut microbiota can be identified prior to the diagnosis of GDM. This study characterized dynamic changes of gut microbiota from the first trimester (T1) to the second trimester (T2) and evaluated their relationship with later development of GDM. Compared with the control group (n = 103), the GDM group (n = 31) exhibited distinct dynamics of gut microbiota, evidenced by taxonomic, functional, and structural shifts from T1 to T2. Linear discriminant analysis (LDA) revealed that there were 10 taxa in T1 and 7 in T2 that differed in relative abundance between the GDM and control groups, including a consistent decrease in the levels of Coprococcus and Streptococcus in the GDM group. While the normoglycemic women exhibited substantial variations of gut microbiota from T1 to T2, their GDM-developing counterparts exhibited clearly reduced inter-time point shifts, as corroborated by the results of Wilcoxon signed-rank test and balance tree analysis. Moreover, cooccurrence network analysis revealed that the interbacterial interactions in the GDM group were minimal compared with those in the control group. In conclusion, lower numbers of dynamic changes in gut microbiota in the first half of pregnancy are associated with the development of GDM.IMPORTANCE GDM is one of the most common metabolic disorders during pregnancy and is associated with adverse short-term and long-term maternal and fetal outcomes. The aim of this study was to examine the connection between dynamic variations in gut microbiota and development of GDM. Whereas shifts in gut microbiota composition and function have been previously reported to be associated with GDM, very little is known regarding the early microbial changes that occur before the diagnosis of GDM. This study demonstrated that the dynamics in gut microbiota during the first half of pregnancy differed significantly between GDM and normoglycemic women. Our findings suggested that gut microbiota may potentially serve as an early biomarker for GDM.

Different characteristics of gut microbiota before and after management of women with gestational diabetes mellitus and the association with blood glucose level

Objective To investigate the gut microbial profiles of gestational mellitus diabetes (GDM) patients before and after treatment, and the relationship between gut microbiota and blood glucose level measured in 75 g oral glucose tolerance test (OGTT). Methods A prospective cohort-based nested case-control study was conducted in Peking University First Hospital from October 2016 to December 2017. Forty-five pregnancies at 24-28 gestational weeks with GDM (GDM group) and 45 healthy gravidas (control group) matched for age and pre-pregnancy body mass index (BMI) were involved. Stool samples of all participants were collected before (24-28 gestational weeks) and after (36-40 gestational weeks) treatment. The V3-V4 region of the 16S rRNA gene was sequenced on the Illumina Hiseq 2500 platform, and the results were analyzed. QIIME software was used for bioinformatics analysis. Student's t-test, Mann-Whitney U test, and Chi-square test were used for statistical analysis. Results (1) Before treatment, the Alpha diversity of the GDM group was significantly reduced compared with that of the control group (Chao1 index: 443.9±72.9 vs 474.0±63.3, t=2.104, P<0.05; Shannon index: 5.6±0.5 vs 6.0±0.5, t=2.002, P<0.05), and a significant difference in Beta diversity was also observed between the two groups (R2=0.04, P<0.05). However, a significant difference was shown in neither Alpha nor Beta diversity between the two groups after the treatment. (2) Before treatment, the relative abundances of Blautia and Faecalibacterium of the GDM group were significantly higher than those of the control group [M (P25-P75): 0.016 (0.009-0.022) vs 0.011 (0.007-0.016), U=782.000; 0.114 (0.076-0.141) vs 0.091 (0.061-0.126), U=752.000; both P<0.05], but the relative abundances of Akkermansia, Odoribacter and Butyricimonas were significantly lower [0.001 (0.000-0.002) vs 0.001 (0.000-0.005), U=745.000; 0.001 (0.000-0.004) vs 0.004 (0.001-0.006), U=766.500; 0.001 (0.000-0.003) vs 0.003 (0.001-0.005), U=710.000; all P<0.05]. (3) A negative relationship was found between the fasting glucose level of OGTT and the relative abundances of Akkermansia, Odoribacter and Butyricimonas (r=-0.325, -0.273 and -0.284; all P<0.05), and between the one-hour-OGTT glucose level and the relative abundances of Akkermansia and Butyricimonas (r=-0.285 and -0.265, both P<0.05). The two-hour-OGTT glucose level was positively related to the relative abundance of Faecalibacterium (r=0.278, P<0.05), but negatively related to the relative abundance of Akkermansia (r=-0.245, P<0.05). The area under the OGTT time-glucose curve was negatively related to the relative abundances of Akkermansia and Butyricimonas (r=-0.321 and -0.264, both P<0.05). Conclusions There are significant differences in gut microbial composition and structure between GDM and healthy pregnant women, which are significantly associated with OGTT blood glucose level. Euglycemia achieved after GDM management could improve gut microbiota disorder. Key words: Diabetes, gestational; Gastrointestinal microbiome; Glucose tolerance test; Blood glucose

Postpartum treatment with liraglutide in combination with metformin versus metformin monotherapy to improve metabolic status and reduce body weight in overweight/obese women with recent gestational diabetes: A double-blind, randomized, placebo-controlled study

BackgroundGestational diabetes (GDM) imparts a high risk of developing diabetes postpartum. Insulin resistance appears to be the major contributor. Liraglutide, a glucagon-like peptide-1 analogue, improves peripheral glucose disposal and reduces body weight. We evaluated whether liraglutide in combination with metformin (MET-LIRA) is more effective than metformin monotherapy (MET-P) in improving insulin action and reducing body weight in overweight prior GDM (pGDM) women. MethodsWomen (n = 153; body mass index (BMI) ≥25 kg/m2; 18–45 y; GDM within 12 months) with metabolic abnormalities were randomized to MET-LIRA (MET-2000 mg, LIRA 1.8 mg SC QD) or MET-P (MET-2000 mg, Placebo QD). Study visits at baseline, 36–40, 56–60 and 80–84 weeks included body weight (BW), BMI, waist circumference and waist-to-height ratio measures. Oral glucose tolerance tests (OGTTs) were performed to assess glycemia, mean blood glucose (MBG), lipids, and compute insulin sensitivity and secretion measures. FindingsSeventy-two (47%) participants completed the study. MET-LIRA therapy was significantly better in improving MBG and insulin sensitivity indices [SIOGTT MET-LIRA from 4.6 (3.2) to 5.9 (2.9) vs. MET-P 5.5 (3.0) to 5.4 (3.2)] and reducing BW and central adiposity [BMI MET-LIRA from 37.2 (8.3) to 33.8 (5.2) vs MET-P 33.8(5.2) to 32.8(6)]. MET–LIRA therapy but not MET-P decreased triglycerides (TRG) and TRG/high density lipoprotein cholesterol (HDL-C) ratios. InterpretationMET-LIRA treatment demonstrated superior efficacy in correcting the metabolic status of pGDM women over 84 weeks of therapy. The addition of liraglutide to metformin therapy resulted in a more dramatic decrease in BW and central adiposity than metformin alone. FundationSupported by an unrestricted investigator initiated grant from Novo Nordisk, Inc. awarded to K.E.H. Meeting presentationThe results from preliminary analyses of this study were presented at 76th meeting of the American Diabetes Association, June 10–14, 2016 New Orleans, LA, and 77th meeting of the American Diabetes Association, June 9–12, 2017San Diego, CA.

The Role of Glycemic Index and Glycemic Load in the Development of Real-Time Postprandial Glycemic Response Prediction Models for Patients With Gestational Diabetes.

The incorporation of glycemic index (GI) and glycemic load (GL) is a promising way to improve the accuracy of postprandial glycemic response (PPGR) prediction for personalized treatment of gestational diabetes (GDM). Our aim was to assess the prediction accuracy for PPGR prediction models with and without GI data in women with GDM and healthy pregnant women. The GI values were sourced from University of Sydney’s database and assigned to a food database used in the mobile app DiaCompanion. Weekly continuous glucose monitoring (CGM) data for 124 pregnant women (90 GDM and 34 control) were analyzed together with records of 1489 food intakes. Pearson correlation (R) was used to quantify the accuracy of predicted PPGRs from the model relative to those obtained from CGM. The final model for incremental area under glucose curve (iAUC120) prediction chosen by stepwise multiple linear regression had an R of 0.705 when GI/GL was included among input variables and an R of 0.700 when GI/GL was not included. In linear regression with coefficients acquired using regularization methods, which was tested on the data of new patients, R was 0.584 for both models (with and without inclusion of GI/GL). In conclusion, the incorporation of GI and GL only slightly improved the accuracy of PPGR prediction models when used in remote monitoring.

973: Long-term maternal metabolic and cardiovascular phenotypes after pregnancies complicated by mild GDM

To evaluate the association of mild GDM and/or obesity on long-term maternal metabolic and cardiovascular markers. Secondary analysis of 5-10 year follow-up from a mild GDM study that included a treatment trial for mild GDM and an observational cohort of women with abnormal 1-hour GCT only. Women who had maternal 1-hour glucose tolerance tests at the follow-up were included. Maternal serum was analyzed using magnetic bead-based multiplex assays to measure insulin levels and cardiovascular markers VEGF, VCAM-1, CD40L, GDF-15, and ST-2. Insulin levels were used to calculate the insulinogenic index (IGI), a measure of pancreatic ß-cell function, and 1/HOMA, a measure of insulin resistance. These markers were compared by parent study GDM status (treated GDM, untreated GDM, and non-GDM) and by obesity at parent study enrollment. Multivariable linear regression estimated the association of GDM status and obesity with the metabolic and cardiovascular markers, adjusting for age, race/ethnicity and years since index pregnancy. 642 women with serum samples available for testing were included in this analysis (Table). Treated GDM and untreated GDM were associated with lower mean differences in log 1/HOMA, compared with non-GDM (-0.24, 95%CI -0.36–-0.12 and -0.15, 95%CI -0.28–-0.03, respectively, Figure). Treated GDM was also associated with lower mean difference in log VCAM (-0.11, 95%CI -0.19–-0.03). GDM status was not associated with IGI or other cardiovascular markers. Obesity was only associated with lower mean difference in log 1/HOMA (-0.42, 95%CI -0.52–-0.32). Women with mild GDM and obese pregnant women are at increased risk for insulin resistance at long term follow-up. Among this population, neither GDM nor obesity was associated with pancreatic ß-cell dysfunction. Treatment of mild GDM may be associated with less angiogenesis, but neither mild GDM nor obesity was associated with other markers of cardiovascular dysfunction 5-10 years after pregnancy.View Large Image Figure ViewerDownload Hi-res image Download (PPT)

Metagenomic analysis reveals gestational diabetes mellitus-related microbial regulators of glucose tolerance.

Recent studies have suggested a possible association between microbiota and gestational diabetes (GDM). However, the results are inconsistent. Our objective was to investigate further the relationship between GDM and microbiota and verify the potential microbial marker. Two complementary approaches were used for the demonstration. First, we compared the gut microbial composition of 23 GDM patients and 26 non-GDM ethnically Chinese Han pregnant women, by using whole-metagenome shotgun sequencing of their stool samples collected at the third trimester. Second, we used Q-PCR (quantitative polymerase chain reaction) to evaluate the gut microbial composition in the stool samples from another cohort of 150 Chinese pregnant women (113 Control and 37 GDM), to further confirm the potential microbial marker. The gut microbiota of GDM women show lower albeit not statistically significant (p = 0.18) alpha diversity at the species level than non-GDM women. However, the species-level beta-diversity or between-sample diversity measured by Bray-Curtis distance shows significant differences (p < 2.2e-16) between the two groups. The species Bacteroides dorei positively correlated with both OGTT (oral glucose tolerance test) 0-Hour (p = 0.0099) and OGTT 1-Hour (p = 0.0070). There is a similar trend between Bacteroides sp. 3_1_33FAA and both OGTT 0-Hour (p = 0.014) and OGTT 1-Hour (p = 0.0101) response variables. The species Alistipes putredinis negatively correlated with OGTT 1-Hour (p = 0.0172) and OGTT 2-Hour (p = 0.0147). Q-PCR validation further confirmed the association between the glucose tolerance loci of Bacteroides dorei and OGTT response. Gut microbiome is related to the diabetic status of Chinese women during pregnancy. Specific species such as Bacteroides dorei associate with glucose response and could be potential monitoring and therapeutic microbial markers for GDM.

IL-1β and IL-10 gene polymorphisms in women with gestational diabetes

Aims Gestational diabetes (GDM) is carbohydrate intolerance occurring in pregnant women. In the GDM pathogenesis, the low-grade inflammation plays a significant role. Various inflammatory mediators are considered to be risk factors leading to GDM development including cytokines. Studies suggest that some cytokines such as: IL-1β and IL-10 play an important role in GDM pathogenesis. The aim of the study was to examine the associations between IL-1β rs16944, and IL-10 rs1800872 gene polymorphisms and GDM. Methods This study included 204 pregnant women with GDM and 207 pregnant women with normal glucose tolerance. The diagnosis of GDM was based on a 75-g oral glucose tolerance test administered at 24–28 weeks’ gestation. Among the pregnant women with GDM, 152 (75%) were treated with diet control alone throughout the pregnancy, whereas the remaining 52 (25%) were treated with diet control and insulin until delivery. Results There were no statistically significant differences in the distribution of IL-1β rs16944 and IL-10 rs1800872 between GDM and healthy women. However among women treated with insulin, we observed the increased frequency of IL-1β rs16944 AA genotype carriers. Additionally, we observed increased daily insulin requirement in women with IL-1β rs16944 AA genotype. Moreover, women with IL-10 rs1800872 AA genotype had higher body mass and BMI before pregnancy as well as higher body mass and BMI increase during pregnancy. Conclusions The results of our study suggest the association between IL-1β rs16944 AA genotype and increased frequency of the need of insulin treatment as well as increased daily insulin requirement.

Independent and concomitant associations of gestational diabetes and maternal obesity to perinatal outcome: A register-based study.

AimsGestational diabetes (GDM) is often accompanied by maternal overweight. Our aim was to evaluate the separate and concomitant effects of GDM and maternal overweight/obesity on perinatal outcomes.MethodsWe used the Finnish Medical Birth Register to identify all 24,577 women with a singleton pregnancy who delivered in 2009 in Finland and underwent an oral glucose tolerance test (OGTT). Women were divided into groups according to the result of OGTT (GDM/no GDM) and pre-pregnancy body mass index (BMI): normal weight (≤24.9 kg/m2), overweight (25.0–29.9 kg/m2), and obese (≥30.0 kg/m2). Primary outcomes included macrosomia, caesarean delivery, and treatment at neonatal ward. Normal weight women without GDM constituted the reference group.ResultsCompared to reference group, overweight or obese women without GDM had an increased risk of macrosomia [odds ratio adjusted for age, parity, smoking and socio-economic status (aOR)1.18 (95% CI 1.09–1.28) and 1.50 (95% CI 1.19–1.88)], and caesarean delivery [aORs 1.17 (95% CI 1.07–1.28) and 1.52 (95% CI 1.37–1.69)], respectively. In normal weight GDM women the risk of macrosomia [aOR 1.17 (95% CI 0.85–1.62)] and caesarean delivery [aOR 1.10 (95% CI 0.96–1.27)] was not significantly increased as compared to normal weight women without GDM. GDM increased the risk of treatment at neonatal ward in all BMI categories and maternal obesity without GDM was also a risk factor for treatment at neonatal ward. Interaction p values between BMI and GDM on these outcomes were <0.001.ConclusionsMaternal overweight and obesity without GDM increased the risk of macrosomia and caesarean delivery when compared to the reference group. These risks were amplified when overweight/obesity was accompanied by GDM. Obesity without GDM was a risk factor for treatment at neonatal ward; GDM increased this risk in all BMI categories. Our results suggest that especially maternal obesity should be considered as a risk factor for adverse pregnancy outcomes and GDM further amplifies this risk.

Demographics of Women With Type 1, Type 2 and Gestational Diabetes Attending a Diabetes and Pregnancy Clinic in 2000-2002, 2010-2012 and 2014-2016.

Abstract Pregnancies complicated by diabetes are increasingly frequent. The Endocrine and Pregnancy Clinic [EPC] at St Joseph’s Health Care London is the stable, local provider of all outpatient pregnancy diabetes care, thereby providing an opportunity to document patient characteristics with time. Methods EPC charts were reviewed for: 2000-2002; 2010-2012; 2014-2016 documenting DM type (T1DM, T2DM, GDM); age; weight; year/week of DM diagnosis; medication/pump use; A1C. Continuous results were analyzed by one-way analysis of variance (ANOVA); non-parametric results were analyzed by Chi-square testing; p Results Total EPC DM women were: 2000-2002: 408; 2010-2012: 571; 2014-2016: 813. GDM women represented 72.8% of EPC patients in 2001-2002 and 88.4% in 2014-2016. Weights and oral medication use increased with time for women with GDM, while insulin use decreased. Pump use in women with T1DM increased by 2010-2012 and 2014-2016 while A1C decreased significantly comparing first to last visits within each time interval. Numbers of women with T2DM increased significantly but weight at first clinic visit was lower over time, while A1C decreased significantly when comparing first to last visits within each time interval. Discussion/Conclusions EPC volumes doubled from 2000 to 2016 with no increase in background deliveries, predominantly due to increased numbers of women GDM, along with a small increase in women with T2DM. These findings may help inform decisions around health care planning and resource allocation.

1409-P: Using Fasting Venous Plasma Glucose (FVPG) to Stratify Risk in Women with Gestational Diabetes (GDM)

Powe et al described variable “defects” (defined as parameter values &amp;lt;25th centile for non GDMs) in OGTT derived insulin secretion (Isecr) and sensitivity (Isens) estimates in GDM. They reported that pregnancy complications relate primarily to low Isens. To explore applicability to routine OGTT data, an analogous but simplified analysis was undertaken, classifying IADPSG GDM women according to FVPG &amp;lt; or ≥ 75th centile for non GDM women (cut-off 4.6 mmol/L - near the cohort mean (SD) of 4.5(0.4) mmol/L). Our multi-ethnic cohort included a diverse group of 6128 untreated women from 5 centers in the blinded epidemiologic HAPO study. Analyses compared outcome frequencies (LGA, excess neonatal (NN) adiposity, NN hypoglycemia, NN hyperinsulinemia, preterm birth, primary C section) with non GDM women and between GDM-FVPG groups using χ2 tests and logistic regression analyses adjusted for maternal age, height, smoking, FH diabetes, BMI at OGTT visit and ethnicity (Table 1). The 25% of GDM women with FVPG &amp;lt; 4.6 mmol/L were at much lower risk of adverse outcomes. Although “mechanistic” classification considering Isecr and Isens may offer insights for treatment, a simpler classification by FVPG performs better and appears simpler for routine use. A modified “two-step” approach for detection and classification of pregnancy hyperglycemia, using FVPG as the first step, deserves consideration. Disclosure D. McIntyre: None. K.S. Gibbons: None. L.R. Madsen: None. R.C. Ma: Advisory Panel; Self; Boehringer Ingelheim International GmbH. Research Support; Self; AstraZeneca, Bayer AG, Pfizer Inc. Stock/Shareholder; Self; GemVCare. Other Relationship; Self; AstraZeneca. D.A. Sacks: None. W.H. Tam: None. P. Catalano: None. Funding National Institutes of Health

353-OR: Comparison of Methods for Classifying Heterogeneity in Gestational Diabetes (GDM) and Association with Outcomes

An underlying principle of the IADPSG GDM classification is that women at similar risk of adverse pregnancy outcomes related to hyperglycemia should be classified similarly. Powe et al have described heterogeneous GDM phenotypes related to impaired insulin secretion and/or insulin sensitivity and reported that pregnancy complications relate primarily to impaired insulin sensitivity. However, their Gen3G cohort was largely Caucasian and GDM women received treatment. Our study was designed to further examine this hypothesis in a diverse population of 6128 untreated women from 5 centers in the blinded epidemiologic HAPO study. Following similar methodology (Impairment = parameter value &amp;lt;25th centile for non GDMs), women with IADPSG GDM were classified as (1) GDMsecr - impaired insulin secretion - using either HOMA β (Hβ) or Insulinogenic index (II); (2) GDMsens - impaired insulin sensitivity - using Matsuda index; (3) Both 1 and 2; (4) GDMND - No Defect. Analyses compared neonatal outcome frequencies (LGA, excess neonatal (NN) adiposity, NN hypoglycemia, NN hyperinsulinemia) with non GDM women and between GDM groups using χ2 tests and logistic regression analyses adjusted for multiple confounders including maternal age, height, smoking, FH of diabetes, BMI at the OGTT visit, ethnicity and HAPO study center. Hβ and II gave divergent results for GDMsecr, with only 25% concordance. GDMND women (10% of all GDM by Hβ, 6% by II) showed outcome frequencies similar to non GDM women. NN hypoglycemia was unrelated to GDM group. In all adjusted analyses, using either Hβ or II, Groups 1-3 showed higher odds (aORs 1.6-3.1; p &amp;lt; 0.01 vs. non GDM) for LGA, NN adiposity and NN hyperinsulinemia. Although Hβ and II identify different women as having defects in insulin secretion, both may contribute to detection of a lower risk group of GDMND women. Beyond this, the division of women according to insulin secretion and insulin sensitivity status did not permit additional risk stratification. Disclosure D. McIntyre: None. L.R. Madsen: None. K.S. Gibbons: None. D.A. Sacks: None. R.C. Ma: Advisory Panel; Self; Boehringer Ingelheim International GmbH. Research Support; Self; AstraZeneca, Bayer AG, Pfizer Inc. Stock/Shareholder; Self; GemVCare. Other Relationship; Self; AstraZeneca. W.H. Tam: None. P. Catalano: None.

355-OR: Is Classification of GDM Phenotypes Dependent on Ethnicity?

Clinical experience suggests that diverse clinical phenotypes exist within the broader diagnosis of GDM. Recent published analysis from a single center outlined heterogeneity in GDM with respect to insulin secretion and sensitivity, defining four GDM phenotypes: 1) GDMsecr (&amp;lt;25th centile HOMA-β for non-GDM); 2) GDMsens (&amp;lt;25th centile Matsuda Index for non-GDM); 3) GDMmixed (both GDMsecr and GDMsens); 4) no defect (neither GDMsecr and GDMsens). Classification using these phenotypes is associated with adverse outcomes. It is unknown whether adjustment for ethnicity may provide stronger associations with outcome prediction. Using data from 5 centers in the HAPO study, GDM women were classified into one of four phenotypes in two ways: 1) whole sample cut-offs; and 2) ethnic-specific glycemic thresholds. Descriptive characteristics were compared between the five groups (four GDM phenotypes + non-GDM), and multivariable analysis adjusted for BMI, center and key demographic and clinical characteristics. Of the 6128 women, 2442 (40%) were caucasian, 294 (4.8%) black, 1556 (25.4%) Hispanic, 1616 (26.4%) Asian and 220 (3.6%) other ethnicity; ethnicity was closely related to study center. Seventeen percent were classified as GDM (n=1047), with slightly higher GDM frequency for black (20.1%) and Hispanic women (23.3%). There was 83.9% agreement between whole-sample and ethnic-specific classification into GDM phenotypes. There was a significant relationship (p&amp;lt;0.05) between one or more GDM phenotypes and LGA, primary CS, neonatal hyperinsulinemia and/or fetal adiposity. Despite minor changes in the adjusted odds ratios, there were no statistically significant changes in the relationship between GDM phenotype and outcome when comparing whole sample cut-offs and ethnic-specific cut-offs. Where available, ethnic-specific cut-offs should be used to define GDM phenotype to assist in identifying GDM women at higher risk of adverse outcome, however whole-sample cut-offs can be used with confidence in their absence. Disclosure K.S. Gibbons: None. D. McIntyre: None. R.C. Ma: Advisory Panel; Self; Boehringer Ingelheim International GmbH. Research Support; Self; AstraZeneca, Bayer AG, Pfizer Inc. Stock/Shareholder; Self; GemVCare. Other Relationship; Self; AstraZeneca. W. Tam: None. L.R. Madsen: None. D.A. Sacks: None. P. Catalano: None.

1396-P: Lessons Learned from Implementing a Dietician-Led Low Risk Model of Care

Research from the U.S. and Australia indicates that individualized medical nutrition therapy provided by a Registered Dietician over a minimum of three appointments can reduce pharmacotherapy requirements for women with GDM. We used an implementation science approach to develop a dietician-led model of care for low risk GDM women. Our evaluation used a pre-post intervention comparison, with primary outcomes of pharmacotherapy use and adherence to clinical guidelines which includes the recommendation of three dietician appointments. Although there were significantly more women who received best-practice dietetic care in the post-intervention cohort, pharmacotherapy use increased (Table). However, other changes over time need to be considered when interpreting these results. Women in the post-intervention cohort were more likely to: have been diagnosed before 24 weeks; have had previous GDM; and be prescribed metformin (Table). Lessons learned included: timing of dietician appointments; ongoing facilitation of the implementation process; workforce engagement; lower targets for commencing pharmacotherapy; and increased surveillance of low-risk women, all of which may have resulted in higher pharmacotherapy conversion rates. Our results have highlighted the importance of measuring process outcomes alongside clinical outcomes and using an implementation science approach when aiming to provide best-practice care. Disclosure N.J.L. Meloncelli: None. A.G. Barnett: None. S.J. de Jersey: None. Funding Health Practitioner Research Scheme

2412-PUB: Demographics of Women with Gestational Diabetes Attending a Diabetes and Pregnancy Clinic: 2000-2002, 2010-2012, and 2014-2016

Background: Numbers of women attending Diabetes and Pregnancy Clinics (DPC) are increasing. Potential reasons include: obesity; fertility intervention access; diagnostic changes for gestational diabetes (GDM). The DPC in London Ontario sees all pregnant women with diabetes within the catchment area with stable clinic structure and procedures. Longitudinal characteristics of GDM women were documented for demographic insights. Methods: DPC pregnancy charts were assessed for 2000-2002, 2010-2012 and 2014-2016. Data were abstracted for: age; weight, infertility interventions; GDM diagnostic method. Continuous results were analyzed by one-way analysis of variance (ANOVA), non-parametric results by Chi-square testing; p≤ 0.05 signifying significance. Conclusions: Over the study interval, women with a GDM diagnosis increased 240%. The change may be related to obesity; changes to GDM diagnostic criteria and week of testing; but not late pregnancy weight gain or use of fertility interventions. Disclosure P. Khanna: None. K. Anukam: None. L. Chow: None. E. Brydges: None. S.L. Liu: Consultant; Self; Novo Nordisk Inc., Sanofi. Research Support; Self; Physicians' Services Inc. Foundation. J. Mahon: None. T.R. Joy: Speaker's Bureau; Self; Amgen Inc., Novo Nordisk Inc., Sanofi. Other Relationship; Self; Amgen Inc., AstraZeneca, Novo Nordisk Inc. R.M. McManus: None.

Placental extracellular vesicles express active dipeptidyl peptidase IV; levels are increased in gestational diabetes mellitus

ABSTRACTGestational diabetes mellitus (GDM) is the most common metabolic disorder in pregnancy and is characterized by insulin resistance and decreased circulating glucagon-like peptide-1 (GLP-1). GDM resolves rapidly after delivery implicating the placenta in the disease. This study examines the biological functions that cause this pathology. The placenta releases syncytiotrophoblast-derived extracellular vesicles (STB-EVs) into the maternal circulation, which is enhanced in GDM. Dipeptidyl peptidase IV (DPPIV) is known to play a role in type 2 diabetes by breaking down GLP-1, which in turn regulates glucose-dependent insulin secretion. STB-EVs from control and GDM women were analysed. We show that normal human placenta releases DPPIV-positive STB-EVs and that they are higher in uterine than paired peripheral blood, confirming placental origin. DPPIV-bound STB-EVs from normal perfused placentae are dose dependently inhibited with vildagliptin. DPPIV-bound STB-EVs from perfused placentae are able to breakdown GLP-1 in vitro. STB-EVs from GDM perfused placentae show greater DPPIV activity. Importantly, DPPIV-bound STB-EVs increase eightfold in the circulation of women with GDM. This is the first report of STB-EVs carrying a biologically active molecule that has the potential to regulate maternal insulin secretion.

Barriers for detection and management of gestational diabetes mellitus in southern Ethiopia: A qualitative study

BackgroundGestational diabetes mellitus (GDM) complicates the health of mother and child not only in the short term but also in the long term basis. Addressing GDM through early detection and proper management is vital to improve maternal and child health. Identifying existing barriers for detection and management is important for policy improvement. This study aims to explore barriers for detection and management of GDM in Wolaita Zone, Southern Ethiopia. MethodsA qualitative study was conducted. Health professionals working in antenatal clinic, delivery, and other maternal health services were selected purposively. A total of 18 in-depth interviews were done. The transcripts were imported into NVIVO version 12 software packages. A qualitative thematic analysis approach was used to analyze the data. ResultsScreening of women for GDM was done based on the risk factor assessment within 24–28 weeks of gestational age. The participants mentioned that they made diagnosis of GDM based on the World Health organization criteria. Barriers for detection and management of GDM include; lack of standard guidelines and protocols, lack of awareness among mid-level health care providers on GDM, inadequate trained health care providers, shortage of supplies and equipment and late antenatal care visits. ConclusionsPolicy makers and health care leadership need to address challenges by availing standard guidelines and protocols, providing on job training for health care providers, fulfilling supplies and consumables and working on early antenatal visits of pregnant mothers.

Early vs. standard screening and treatment of gestational diabetes in high-risk women – An attempt to determine relative advantages and disadvantages

Background and aimsScreening for Gestational Diabetes (GDM) is usually recommended between 24 and 28 weeks of pregnancy; however available evidence suggests that GDM may be already present before recommended time for screening, in particular among high-risk women as those with prior GDM or obesity. The purpose of this retrospective study was to evaluate whether early screening (16–18 weeks) and treatment of GDM may improve maternal and fetal outcomes. Methods and resultsIn 290 women at high-risk for GDM, we analyzed maternal and fetal outcomes, according to early or standard screening and GDM diagnosis time. Early screening was performed by 50% of high-risk women. The prevalence of GDM was 62%. Among those who underwent early screened, GDM was diagnosed at the first evaluation in 42.7%. Women with early diagnosis were more frequently treated with insulin and had a slightly lower HbA1c than women with who were diagnosed late. No differences were observed in the prevalence of Cesarean section, operative delivery, gestational age at the delivery, macrosomia, neonatal weight, Ponderal Index and Large-for-Gestational-Age among women with early or late GDM diagnosis or NGT. However, compared to NGT women, GDM women, irrespective of the time of diagnosis, had a lower gestational weight gain, lower prevalence of macrosomia (3.9% vs. 11.4%), small (1.7% vs. 8.3%) as well as large for gestational age (3.3% vs. 16.7%), but higher prevalence of pre-term delivery (8.9% vs. 2.7%). ConclusionEarly vs. standard screening and treatment of GDM in high-risk women is associated with similar short-term maternal-fetal outcomes, although women with an early diagnosis were treated to a greater extent with insulin therapy.

Mitochondrial-related gene associated to obesity can be modulated by in utero hyperglycemic environment

We investigated whether mitochondrial-related genes and proteins are modulated by hyperglycemia promoted by gestational diabetes (GDM), thereby increasing neonate obesity predisposition. 19 healthy pregnant women, 16 pregnant women with GDM and their respective neonates were enrolled. Additionally, 19 obese and 19 eutrophic adults were recruited as a reference population. Umbilical cord, peripheral blood and placental (villous and decidua) tissues were collected to evaluate SOD2, PPAR-α and PPARGC-1β and their respective protein expressions. Data from the reference population confirmed that the three genes and proteins were overexpressed in blood cells of obese compared to eutrophic subjects. Only SOD2 was found upregulated in placental villous (fetal side) tissue of GDM women. Therefore, our findings showed an interaction between the hyperglycemic environment and SOD2 modulation, but also indicated that none of the three genes is useful as potential biomarkers for obesity development.

Metformin-treated-GDM has lower risk of macrosomia compared to diet-treated GDM- a retrospective cohort study

Background: The diagnosis of gestational diabetes (GDM) has undergone several revisions. The broad adoption of the 2013 WHO criteria for hyperglycemia in pregnancy has increased the prevalence of GDM with no apparent benefit on pregnancy outcomes. The study aims to investigate the pregnancy outcomes in women with GDM diagnosed based on the WHO criteria compared to a control group; the impact of other confounders; and the difference in outcomes between GDM women who needed pharmacotherapy (GDM-T) and those who did not (GDM-D).Methods: This is a retrospective cohort study that included GDM women compared to normoglycemic controls between March 2015 and December 2016 in the Women’s Hospital, Qatar.Results: The study included 2221 women; of which 1420 were normoglycemic, and 801 were GDM (358 GDM-D and 443 GDM-T). At conception, GDM women were older (mean age 32.5 ± 5.4 versus 29.6 ± 5.6 years, p<.001) and had higher prepregnancy BMI (mean BMI 32.2 ± 6.2 versus 28.2 ± 6.1 kg/m2, p<.01) compared to the controls, respectively. After correction for age, prepregnancy weight, and gestational weight gain (GWG); women with GDM had a higher risk of preterm labor (OR: 1.72; 95% CI: 1.32–2.23), large for gestational age (GA) (OR: 1.67; 95% CI: 1.22–2.29), neonatal ICU admission (OR: 1.57; 95% CI: 1.15–2.13), and neonatal hypoglycemia (OR: 3.22; 95% CI: 2.06–5.03). At conception, GDM-T women were older (mean age 33.3 ± 5.0 versus 31.5 ± 5.7 years, p<.001) and had higher BMI (mean BMI 32.9 ± 6.3 versus 231.2 ± 6.0 kg/m2, p=.01) compared to GDM-D, respectively. Metformin was used in 90.7% of the GDM-T women. Women in the GDM-T group had lower GWG/week compared to GDM-D (−0.01 ± 0.7 versus 0.21 ± 0.5 kg/week; p<.001). After correcting for age, prepregnancy weight and GWG; GDM-T had a higher risk of preterm labor (OR: 1.66; 95% CI: 1.20–2.22), and C-section (OR: 1.37, 95% CI: 1.02–1.85) and reduced risk of macrosomia (OR: 0.56; 95% CI: 0.32–0.96) and neonatal hypoglycemia (OR: 0.49; 95% CI: 0.28–0.82).Conclusion: In addition to hyperglycemia, the adverse effects of GDM on pregnancy outcomes are multifactorial and includes maternal age, maternal obesity, and gestational weight gain. Treatment with metformin reduces maternal weight gain, the risk of macrosomia and neonatal hypoglycemia compared to diet alone.

Metabolic follow-up at one year and beyond of women with gestational diabetes treated with insulin and/or oral hypoglycaemic agents: study protocol for the identification of a core outcomes set using a Delphi survey

BackgroundGestational diabetes (GDM) is associated with an increased lifetime risk for the development of glucose abnormalities, metabolic syndrome, cardiovascular disease, depression and tumours. Despite this high risk of additional comorbidities, there is no standardised approach to the long-term follow-up of women with a previous diagnosis of GDM. Also, there is no standardisation of outcome selection and reporting in studies involving this population. This increases the risk of reporting bias and reduces the possibility of meaningful comparisons between studies. The aim of this study is to develop a protocol for a core outcome set (COS) for the metabolic follow-up at 1 year and beyond of women with previous GDM treated with insulin and/or oral hypoglycaemic agents.Methods/designThis protocol will describe the steps that will be taken in order to develop the COS. The study will consist of three parts: (1) A systematic review of the literature of the outcomes reported in previous randomised controlled trials of the follow-up at 1 year and beyond of women with GDM treated with insulin and/or oral hypoglycaemic agents; (2) A three-round, online Delphi survey with key stakeholders in order to prioritise these outcomes; and (3) A consensus meeting where the final COS will be decided.DiscussionThe proposed protocol is the first step in developing a COS that will bring consistency and uniformity to outcome selection and reporting in GDM women treated with insulin and/or oral hypoglycaemic agents.