Glucose Metabolism In Pregnancy Research Articles

A Longitudinal Study of Plasma Glycated Albumin across Pregnancy and Associations with Maternal Characteristics and Cardiometabolic Biomarkers.

Glycated albumin (GA) has recently been proposed as a screening marker for diabetes among non-pregnant individuals. However, data on GA during pregnancy are sparse and lacking among women of diverse race/ethnicity. We investigated longitudinal concentrations of GA among multiracial pregnant women in the National Institute of Child Health and Human Development (NICHD) Fetal Growth Studies-Singletons. We quantified GA and cardiometabolic biomarkers using longitudinal plasma samples collected at 10 to 14, 15 to 26 (fasting), 23 to 31, and 33 to 39 gestational weeks from 214 pregnant women without gestational diabetes. We examined the distribution of GA across pregnancy and its association with participants' characteristics including race/ethnicity, pre-pregnancy body mass index (ppBMI), and selected cardiometabolic biomarkers. GA trajectories were estimated using a latent class approach. Medians (interquartile range) of GA concentrations were 12.1% (10.6%-13.4%), 12.5% (10.7%-13.8%), 12.4% (10.9%-13.5%), and 11.5% (10.4%-12.5%) at 10 to 14, 15 to 26, 23 to 31, and 33 to 39 weeks, respectively. There were no significant differences in the pattern among different race/ethnic groups (P > 0.53). A minority of women exhibited a GA trajectory characterized by a high concentration of GA at 15 to 26 weeks. GA concentrations were inversely related to ppBMI and plasma low-density lipoprotein and triglyceride concentrations, but were not significantly related to hemoglobin A1c, fasting insulin, or glucose over pregnancy. In this study of individuals who were normoglycemic before pregnancy, plasma GA concentrations stayed relatively constant over pregnancy, decreasing only in late pregnancy. GA concentrations were inversely related to ppBMI and suboptimal lipid profiles, but did not appear to be a sensitive marker for glucose metabolism in pregnancy.

1174-P: Characterization of Glucose Levels in Pregnancy Measured by Blood Glucose Testing or CGM Monitoring after a 50-g Screening or a 75-g or 100-g OGTT

Glucose challenge testing (GCT) is standard diagnostic approach for gestational diabetes (GDM). Using CGM glucose values to characterize glycemia during GCT is not well described. CGM and blood glucose (BG) values were matched with closest CGM value ±5 min of each reported BG time. GDM diagnosed by standard glucose thresholds for 50g GCT, 75g and 100g OGTTs. GCT (n=543, mean gestation 28 wks) showed mean±SD 1 hr BG of 117±28 mg/dL, while matched CGM mean BG was 126±36 mg/dL. The 1 hr BG was ≥135 mg/dL in 24% of GCT vs. 38% by CGM. OGTT (75g) (n=44, mean gestational age 28 wks) showed mean±SD fasting, 1 hr and 2 hr BG of 84±9 mg/dL, 156±33 mg/dL, and 119±26 mg/dL. OGTT (100g) (n=77, mean gestational age 29 wks) showed mean±SD fasting, 1 hr, 2 hr, and 3 hr BG of 82±9 mg/dL, 166±31 mg/dL, 137±27, and 101±27 mg/dL. CGM levels during GCT and both OGTT were similar but slightly higher for each time point; maximum glucose and glucose excursions were also similar between each test vs CGM. Those diagnosed with GDM had consistently higher CGM glucoses than those without GDM (Figure 1). CGM during GCT/OGTT demonstrates CGM correlates to BG, although consistently slightly higher for all 3 glucose tests, regardless of glucose load or timing of measurement. Correlating CGM values to obstetric outcomes would help further describe the role of CGM for diagnosing GDM and improving glucose metabolism in pregnancy. Disclosure A.L.Carlson: Advisory Panel; MannKind Corporation, Novo Nordisk, Research Support; Abbott Diabetes, Dexcom, Inc., Eli Lilly and Company, Medtronic, Novo Nordisk, Insulet Corporation, UnitedHealth Group, Sanofi. J.Sibayan: None. P.Calhoun: None. C.Durnwald: None. R.Beck: Consultant; Eli Lilly and Company, Novo Nordisk, Diasome, Insulet Corporation, Research Support; Tandem Diabetes Care, Inc., Beta Bionics, Inc., Dexcom, Inc., Bigfoot Biomedical, Inc., Medtronic, Ascensia Diabetes Care, Roche Diabetes Care, Eli Lilly and Company, Novo Nordisk. Z.Li: None. E.Norton: None. R.M.Bergenstal: Advisory Panel; Abbott Diabetes, Eli Lilly and Company, Medtronic, Novo Nordisk, Roche Diabetes Care, Zealand Pharma A/S, Consultant; Ascensia Diabetes Care, Bigfoot Biomedical, Inc., CeQur SA, Dexcom, Inc., Hygieia, Onduo LLC, Sanofi, Vertex Pharmaceuticals Incorporated, Research Support; Abbott Diabetes, Dexcom, Inc., Eli Lilly and Company, Insulet Corporation, Medtronic, Novo Nordisk, Sanofi, UnitedHealth Group. M.L.Johnson: Research Support; Abbott, Lilly, Insulet Corporation, NIH - National Institutes of Health, Patient-Centered Outcomes Research Institute, Novo Nordisk, Tandem Diabetes Care, Inc., Medtronic, Hemsley Charitable Trust, Jaeb Center for Health Research. S.Dunnigan: None. M.Banfield: None. K.J.Krumwiede: None. Funding The Leona M. and Harry B. Helmsley Charitable Trust; United Health Group

Roux-en-Y Gastric Bypass Increases Glycemic Excursions During Pregnancy and Postpartum: A Prospective Cohort Study.

Roux-en-Y gastric bypass (RYGB) and pregnancy markedly alter glucose metabolism, but evidence on glucose metabolism in pregnancy after RYGB is limited. Thus, the aims of the Bariatric Surgery and Consequences for Mother and Baby in Pregnancy study were to investigate interstitial glucose (IG) profiles during pregnancy, risk factors associated with hypoglycemia, and the association between fetal growth and hypoglycemia in pregnant women previously treated with RYGB, compared with control participants. Twenty-three pregnant women with RYGB and 23 BMI- and parity-matched pregnant women (control group) were prospectively studied with continuous glucose monitoring in their first, second, and third trimesters, and 4 weeks postpartum. Time in range (TIR) was defined as time with an IG level of 3.5-7.8 mmol/L. Women with RYGB were 4 years (interquartile range [IQR] 0-7) older than control participants. Pregnancies occurred 30 months (IQR 15-98) after RYGB, which induced a reduction in BMI from 45 kg/m2 (IQR 42-54) presurgery to 32 kg/m2 (IQR 27-39) prepregnancy. Women with RYGB spent decreased TIR (87.3-89.5% vs. 93.3-96.1%; P < 0.01) owing to an approximately twofold increased time above range and increased time below range (TBR) throughout pregnancy and postpartum compared with control participants. Women with increased TBR had a longer surgery-to-conception interval, lower nadir weight, and greater weight loss after RYGB. Finally, women giving birth to small-for-gestational age neonates experienced slightly increased TBR. Women with RYGB were more exposed to hypoglycemia and hyperglycemia during pregnancy compared with control participants. Further research should investigate whether hypoglycemia during pregnancy in women with RYGB is associated with decreased fetal growth.

Assessment of glucose levels in pregnant women with history of COVID-19 in a case-control study.

Severe Acute Respiratory Syndrome CoronaVirus 2 (SARS-CoV-2) infection may negatively affect glucose metabolism. This study aims to assess glucose levels, prevalence of gestational diabetes mellitus (GDM) and perinatal outcome in women with history of COVID-19. To this purpose, a group of 65 patients with history of COVID-19 and 94 control patients were retrospectively recruited among pregnant women who attended the pregnancy outpatient department between 01/2020 and 02/2022. Glucose data from an oral glucose tolerance test (OGTT), GDM status and obstetric complications were assessed. We observed no differences in average (p = 0.37), fasting (p = 0.62) or post-load glucose concentrations (60 min: p = 0.19; 120 min: p = 0.95) during OGTT. A total of 15 (23.1%) women in the COVID-19 group and 18 (19.1%) women in the control group developed GDM (p = 0.55). Moreover, caesarean section rate, weight percentiles and pregnancy outcomes were comparable between the groups (p = 0.49). In conclusion, in this study we did not identify a possible impact of COVID-19 on glucose metabolism in pregnancy, especially with regard to glucose concentrations during the OGTT and prevalence of GDM.

Fatty liver indices and their association with glucose metabolism in pregnancy – An observational cohort study

AimsNon-invasive hepatic steatosis indices can be used to assess the risk for metabolic (dysfunction) associated fatty liver disease (MAFLD). This may be helpful to detect metabolic disorders in pregnancy, specifically gestational diabetes (GDM). We aimto examine the association of these indices with parameters of glucose metabolism. Methods109 women underwent a metabolic characterization at 16 weeks of gestation andwere classified according to the fatty-liver index (FLI) andhepatic-steatosis index (HSI) into low (G1), intermediate (G2) and high risk (G3). At 26 weeks, participants received an oral glucose tolerance test (OGTT) to assess insulin action, β-cell function and GDM status. ResultsBoth MAFLD indices wereassociated with impaired insulin sensitivityand compensatory increase of insulin release. G3 groups showedimpaired insulin action. The higher circulating insulin concentrations were not able to compensate for insulin resistance in women with higher MAFLD scores, resulting in an increased risk of GDM(OR: 1.05, 95% CI 1.03 to 1.08, p < 0.001 for FLI). MAFLD scores were associated with fetal overgrowth. ConclusionsMaternal MAFLD represents a high-risk obstetric condition. Hepatic steatosis indices are associated with impaired glucose regulation and may provide a useful tool for early risk assessment for impaired glucose metabolism.

Physical Activity and Sedentary Time in Pregnancy: An Exploratory Study on Oxidative Stress Markers in the Placenta of Women with Obesity.

Regular moderate-to-vigorous physical activity (MVPA) and reduced sedentary time (ST) improve maternal glucose metabolism in pregnancy. More MVPA and less ST outside pregnancy increase antioxidant capacity, hence, are beneficial in preventing oxidative stress. The placenta is the first line of defense for the fetus from an adverse maternal environment, including oxidative stress. However, effects of MVPA and ST on oxidative stress markers in the placenta are unknown. The purpose of this study was to assess the association of MVPA and ST in pregnancy with oxidative stress markers in placentas of overweight/obese women (BMI ≥ 29 kg/m2). MVPA and ST were objectively measured with accelerometers at <20 weeks, 24–27 and 35–37 weeks of gestation. Using linear Bayesian multilevel models, the associations of MVPA and ST (mean and changes) with mRNA expression of a panel of 11 oxidative stress related markers were assessed in 96 women. MVPA was negatively correlated with HSP70 mRNA expression in a sex-independent manner and with GCLM expression only in placentas of female fetuses. ST was positively associated with HO-1 mRNA expression in placentas of male neonates. None of the other markers were associated with MVPA or ST. We speculate that increasing MVPA and reducing ST attenuates the oxidative stress state in placentas of obese pregnant women.

Prediction of birth weight in pregnancy with gestational diabetes mellitus using an artificial neural network.

Gestational diabetes mellitus (GDM) is common during pregnancy, with the prevalence reaching as high as 31.0% in some European regions (McIntyre et al., 2019). Dysfunction of the glucose metabolism in pregnancy can influence fetal growth via alteration of the intrauterine environment, resulting in an increased risk of abnormal offspring birth weight (McIntyre et al., 2019). Infants with abnormal birth weight will be faced with increased risks of neonatal complications in the perinatal period and chronic non-communicable diseases in childhood and adulthood (Mitanchez et al., 2015; McIntyre et al., 2019). Therefore, accurate estimation of birth weight for neonates from women with GDM is crucial for more sensible perinatal decision-making and improvement of perinatal outcomes. Timely antenatal intervention, with reference to accurately estimated fetal weight, may also decrease the risks of adverse long-term diseases.

Hypoglycemia in Pregnancies Following Gastric Bypass-a Systematic Review and Meta-analysis.

The aims of this systematic review were to identify the prevalence of hypoglycemia among pregnant women treated with gastric bypass, and risk factors of hypoglycemic events in pregnancy. We searched MEDLINE, EMBASE, Cochrane, and Scopus databases from inception to April 6, 2021. Six studies investigating glucose metabolism in pregnancy following gastric bypass were included (n = 330). As assessed by the oral glucose tolerance test and continuous glucose monitoring, 57.6% (95% CI [40.1, 75.1]) of women with gastric bypass were exposed to hypoglycemia during pregnancy. No studies performed the mixed meal test, and no studies reported on risk factors associated with hypoglycemia. Further studies are required to determine the magnitude of hypoglycemia in these women's everyday-life using continuous glucose monitoring and mixed meal test.

Associations between gene expression of magnesium transporters and glucose metabolism in pregnancy

To assess the relationship between gene expressions of the magnesium transporters and glucose parameters in pregnant women. A cohort of women without ongoing or prior medical illnesses was recruited at the start of an early singleton pregnancy. Expression levels of the magnesium transporters-SLC41A1, CNNM2, MAGT1, TRPM6, and TRPM7-were assessed in the peripheral leukocytes, while total calcium and magnesium were assessed in the serum between 10 and 13 weeks gestation. Glucose parameters were assessed between 24 and 28 weeks gestation using the 75g oral glucose tolerance test. A total of 208 patients were included in the study. The expressions of the magnesium transports were generally unrelated to age, body mass index (BMI), or serum levels of calcium and magnesium. The magnesium transporters were correlated with each other at baseline (correlation coefficients: 0.31 to 0.51). BMI was a strong predictor of fasting glucose levels, while both BMI and age were strong predictors of post-load glucose levels. The expression of TRPM7 was found to be predictive of 1-h post-load blood glucose after accounting for the effects of age and BMI (β=-0.196, p=0.020). The increased maternal expression of the magnesium transporter TRPM7 may be associated with decreased glucose tolerance in pregnant women. In particular, the association between TRPM7 and 1-h post-load glucose levels was found to be independent of the effects of age and BMI. Future studies are needed to determine whether a mechanistic relationship can be demonstrated between TRPM7 and glucose metabolism.

Placental Endocrine Activity: Adaptation and Disruption of Maternal Glucose Metabolism in Pregnancy and the Influence of Fetal Sex.

The placenta is an endocrine fetal organ, which secretes a plethora of steroid- and proteo-hormones, metabolic proteins, growth factors, and cytokines in order to adapt maternal physiology to pregnancy. Central to the growth of the fetus is the supply with nutrients, foremost with glucose. Therefore, during pregnancy, maternal insulin resistance arises, which elevates maternal blood glucose levels, and consequently ensures an adequate glucose supply for the developing fetus. At the same time, maternal β-cell mass and function increase to compensate for the higher insulin demand. These adaptations are also regulated by the endocrine function of the placenta. Excessive insulin resistance or the inability to increase insulin production accordingly disrupts physiological modulation of pregnancy mediated glucose metabolism and may cause maternal gestational diabetes (GDM). A growing body of evidence suggests that this adaptation of maternal glucose metabolism differs between pregnancies carrying a girl vs. pregnancies carrying a boy. Moreover, the risk of developing GDM differs depending on the sex of the fetus. Sex differences in placenta derived hormones and bioactive proteins, which adapt and modulate maternal glucose metabolism, are likely to contribute to this sexual dimorphism. This review provides an overview on the adaptation and maladaptation of maternal glucose metabolism by placenta-derived factors, and highlights sex differences in this regulatory network.

Associations between an integrated component of maternal glycemic regulation in pregnancy and cord blood DNA methylation.

Background: Previous studies suggest that fetal programming to hyperglycemia in pregnancy is due to modulation of DNA methylation (DNAm), but they have been limited in their maternal glycemic characterization. Methods: In the Gen3G study, we used a principal component analysis to integrate multiple glucose and insulin values measured during the second trimester oral glucose tolerance test. We investigated associations between principal components and cord blood DNAm levels in an epigenome-wide analysis among 430 mother-child pairs. Results: The first principal component was robustly associated with lower DNAm at cg26974062 (TXNIP;p =9.9×10-9) in cord blood. TXNIP is a well-known DNAm marker for type 2 diabetes in adults. Conclusion: Wehypothesize that abnormal glucose metabolism in pregnancy may program dysregulation of TXNIP across the life course.

956-P: A Longitudinal Study of Plasma Glycated Albumin in Pregnancy: Findings from a Multiracial U.S. Pregnancy Cohort

Background: Glycated albumin (GA) represents a useful tool reflecting glycemic homeostasis over a period of 3 weeks and has been recently proposed as a screening marker for diabetes among non-pregnant individuals. However, data on GA during pregnancy are sparse in general and lacking among women of diverse race/ethnicity. We aimed to investigate longitudinal levels of GA in pregnancy among U.S. women of multi-race/ethnicity. Methods: We quantified GA and cardiometabolic biomarkers using blood samples collected at 8-13, 15-26 (fasting sample), 26-31, and 33-39 gestational weeks from 214 pregnant women without gestational diabetes in the NICHD Fetal Growth Studies-Singletons. We examined distributions of GA across pregnancy and their associations with major characteristics of study participants such as race/ethnicity, pre-pregnancy body mass index (BMI), fetal sex, and selected cardiometabolic biomarkers. Results: Overall, GA tended to increase from early pregnancy to 2nd trimester and decrease through the 3rd trimester; medians (inter-quartile range) were 12.1% (10.6-13.4), 12.5 (10.7-13.8),12.4 (10.9-13.5) and 11.5 (10.4-12.5) at 8-13, 15-26, 26-31, and 33-39 gestational weeks, respectively. A similar pattern was observed across race/ethnicity groups (p for interaction =0.71). At 8-13 gestational weeks, GA concentrations were significantly and inversely related to pre-pregnancy BMI, waist circumference and waist/hip ratio, and plasma HDL and adiponectin levels, but significantly and positively related to triglyceride levels. Interestingly, GA levels were neither significantly related to HbA1c over pregnancy, nor to fasting inulin, glucose, or HOMA-IR. GA levels did not vary significantly by race/ethnicity or fetus sex. Conclusion: GA appeared not a sensitive marker for glucose metabolism in pregnancy, although it was significantly related to pre-pregnancy adiposity measures and some cardiometabolic biomarkers during pregnancy. Disclosure C. Zhang: None. J. Wu: None. S. Hinkle: None. D. B. Sacks: Research Support; Self; Sebia, Trinity Biotech plc.

Association between maternal triglycerides and disturbed glucose metabolism in pregnancy

AimsDyslipidemia in pregnancy is associated with adverse pregnancy outcomes as elevated triglycerides might be considered as a risk factor for hyperglycemia and gestational diabetes. As only a few studies have addressed the association between maternal triglycerides and glucose metabolism, we aimed to explore the pathophysiologic associations of moderate hypertriglyceridemia and maternal glucose metabolism in pregnancy.MethodsSixty-seven pregnant women received a detailed metabolic characterization at 12+0–22+6 weeks of gestation by an extended 2h-75g OGTT (oral glucose tolerance test); with measurements of glucose, insulin and C-peptide at fasting and every 30 min after ingestion and assessment of triglycerides at fasting state. All examinations were repeated at 24+0–27+6 weeks of gestation.ResultsElevated triglycerides in early gestation were associated with insulin resistance and β-cell dysfunction. Mean glucose concentrations during the OGTT in early pregnancy were already higher in women with hypertriglyceridemia as compared to women with triglycerides in the normal range. A higher degree of insulin resistance and increased OGTT glucose levels were also observed when metabolic assessments were repeated between 24 and 28 weeks of gestation. Of note, elevated triglycerides at early gestation were associated with development of gestational diabetes by logistic regression (odds ratio: 1.16, 95%CI: 1.03–1.34, p=0.022 for an increase of 10 mg/dl).ConclusionsHypertriglyceridemia at the start of pregnancy is closely related to impaired insulin action and β-cell function. Women with hypertriglyceridemia have higher mean glucose levels in early- and mid-gestation. Pregnant women with elevated triglycerides in early pregnancy are at increased risk of developing gestational diabetes.

Genetic Studies of Gestational Diabetes and Glucose Metabolism in Pregnancy.

In this review, we summarize studies investigating genetics of gestational diabetes mellitus (GDM) and glucose metabolism in pregnancy. We describe these studies in the context of the larger body of literature on type 2 diabetes (T2D) and glycemic trait genomics. We reviewed 23 genetic association studies for GDM and performed a meta-analysis, which revealed variants at eight T2D loci significantly associated with GDM after the Bonferroni correction. These studies suggest that GDM and T2D share a number of genetic risk loci. Only two unbiased genome-wide association studies (GWASs) have successfully revealed genetic associations for GDM and related glycemic traits in pregnancy. A GWAS for GDM in Korean women identified two loci (near CDKAL1 and MTNR1B) known to be associated with T2D, though the association of the MTNR1B locus with GDM appears to be stronger than that for T2D. A multi-ethnic GWAS for glycemic traits in pregnancy identified two novel loci (near HKDC1 and BACE2) which appear to be associated with post-load glucose and fasting c-peptide specifically in pregnant women. There are ongoing efforts to use this genetic information, in the form of polygenic scores, to predict risk of GDM and postpartum T2D. The body of literature examining genetic associations with GDM is limited, especially when compared to the available literature on T2D and glycemic trait genomics. Additional genetic discovery for glucose metabolism in pregnant women will require larger pregnancy cohorts and international collaborative efforts. Studies on the clinical implications of these findings are also warranted.

OR08-02 Do OGTT-based Insulin Secretory Response Measures Approximate 1st Phase Insulin Response in Pregnant Women?

Background: We previously showed that 1st phase insulin response increases dramatically in pregnancy, independent of changes in insulin sensitivity. Measurement of 1st phase insulin response requires the use of hyperglycemic clamps or intravenous glucose tolerance tests (IVGTTs) which are rarely performed in pregnant women. Oral glucose tolerance test (OGTT)-based measures of insulin secretory response have not been validated in pregnancy. Methods: In a secondary analysis of a longitudinal study of glucose metabolism in pregnancy, we examined Pearson correlations between OGTT-based insulin secretory response measures and 1st phase insulin response. Forty women were studied pre-pregnancy; 36 returned in early and late pregnancy (12–14 and 34–36 weeks gestation). At each time point, after overnight fasts, an IVGTT and an OGTT were performed on separate days. The 1st phase insulin response was calculated as the incremental area under the curve during the 1st 10 minutes after intravenous administration of a 0.5 g/kg glucose load (or 19g/m2 body surface area if weight >120% ideal body weight). Homeostatic Model Assessment (HOMAB), Insulinogenic index (IGI), Corrected insulin response (CIR), Insulin area under the curve/Glucose area under the curve (AUCins/AUCglu), and the Stumvoll 1st Phase Estimate (Stumvoll) were calculated from insulin and glucose levels measured fasting and 30, 60, 90, 120, and 180 minutes after an oral glucose load (75 grams pre-pregnancy, 100 grams in pregnancy). Results: The best OGTT-based measure for estimation of 1st phase insulin response differed across study timepoints. In early and late pregnancy, AUCins/AUCglu had the strongest correlation with 1st phase insulin response (early: R=0.79, P<0.0001; late: R=0.69, P<0.0001), but was not associated with 1st phase insulin response pre-pregnancy (R=0.32, P=0.08). IGI had the strongest correlation with first phase insulin response pre-pregnancy (R=0.50, P=0.005) and was correlated with 1st phase insulin response in late (R=0.68, P=0.0001), but not early (R=0.36, P=0.07) pregnancy. Stumvoll was the only OGTT-based measure that was significantly correlated with 1st phase insulin response at all timepoints (pre: R=0.44, P=0.01; early: R=0.67, P=0.0001; late: R=0.67, P=0.0001). HOMAB was the weakest correlate of 1st phase insulin response, though the correlation was significant in early pregnancy (pre: R=-0.04, P=0.82; early: R=0.33, P=0.05; late: R=0.18, P=0.28). Conclusion: OGTT-based measures of insulin secretion do not have a consistent relationship with 1st phase insulin response across pre-, early, and late pregnancy. Our findings suggest that Stumvoll can be used in OGTT-based longitudinal studies of insulin secretory response that begin prior to pregnancy and span gestation. For cross-sectional studies in pregnancy, AUCins/AUCglu are the best estimates of 1st phase insulin response.

Exploring abnormal glucose metabolism in pregnancy among Australian Chinese migrants

ObjectiveGestational diabetes mellitus (GDM) is a metabolic disorder of pregnancy that is increasingly prevalent among Chinese women. Few studies have examined whether the migration status of Chinese women contributes to...

354-OR: Physiologic Pathways in Pregnancy Glycemic Regulation Implicated through Genetic Clustering Analysis

Background: Genetic determinants of glycemic regulation in pregnancy are poorly understood. Methods: We studied 35 glycemia-related traits measured during pregnancy and 191 genetic variants identified in prior genome-wide association studies of type 2 diabetes (T2D) or gestational glycemia. Using linear regression, we quantified associations between glucose-raising alleles and traits measured in 582 women at 24-28 weeks gestation. We clustered traits and variants using Bayesian nonnegative matrix factorization (bNMF) to identify physiologic pathways involved in pregnancy glucose metabolism. Results: In a plurality of bNMF iterations (22/50), 5 clusters emerged, with highly weighted traits and loci suggesting distinct physiologic pathways. Cluster 1: reduced insulin secretory response (lower insulin/c-peptide, greater insulin sensitivity); loci included several known or suspected to affect beta-cell function (ABO, CDKN2B, SLC30A8, CDKN1B). Cluster 2: obesity-related hyperglycemia (higher percent body fat, BMI, fasting/post-load glucose); loci included known obesity/T2D loci (MCR4, FTO) and loci previously tied to beta-cell function that associated with higher glucose and greater adiposity pregnant women (MTNR1B, GLP2R). Cluster 3: insulin resistance (reduced insulin sensitivity, higher fasting insulin/c-peptide, greater insulin secretory response); loci included LYPLAL1 and ANKRD55 (known to harbor insulin resistance variants). Cluster 4 traits suggested reduced adiposity with post-load glucose intolerance. Cluster 5 traits suggested a favorable metabolic profile (lower cholesterol and glucose, higher disposition index and insulin sensitivity). Conclusion: Genetic variants can be grouped to identify physiologic mechanisms at play in gestational glycemic regulation. Associations between physiologically-informed variant clusters, gestational diabetes, and related perinatal outcomes await testing in well-powered cohorts. Disclosure C.E. Powe: None. M. Udler: None. C. Allard: None. J. Kim: None. P. Perron: None. L. Bouchard: None. J.C. Florez: None. M. Hivert: None. Funding American Diabetes Association/Pathway to Stop Diabetes (1-15-ACE-26 to M-F.H.); National Institute of Diabetes and Digestive and Kidney Diseases (K23DK113218, K24DK110550); Robert Wood Johnson Foundation; Fonds de la recherche du Québec en santé

Impact of daily incremental change in environmental temperature on beta cell function and the risk of gestational diabetes in pregnant women.

The prevalence of gestational diabetes (GDM) is higher in summer months, possibly reflecting an association between ambient temperature and blood glucose levels. However, the specific exposure and mechanism by which temperature may affect glucose metabolism in pregnancy remains unclear. We systematically evaluated the relationships of environmental temperature and changes therein over varying durations of exposure time with beta cell function, insulin sensitivity and glucose tolerance in women undergoing antepartum screening for GDM. At a mean gestation of 29weeks, 1464 women in Toronto (ON, Canada) underwent an OGTT, from which 318 were diagnosed with GDM. Blood glucose, beta cell function and insulin sensitivity were evaluated in relation to 18 temperature variables: mean temperature and change in temperature on the day of the OGTT and over the preceding 7, 14, 21, 28, 35, 42, 49 and 56days, respectively. Temperature changes in the preceding 14, 21, 28, 35, 42, 49 and 56days (rather than mean temperatures) emerged as independent predictors of blood glucose. These relationships were evident in months where mean daily temperature was rising (February - July), but not in those where it was falling (August - January). Indeed, in February - July, the temperature changes in the preceding 21, 28 and 35days emerged as predictors of both poorer beta cell function and higher blood glucose. Moreover, in February - July, the changes in temperature in the preceding 21days (OR 1.16, 95% CI 1.01, 1.33) and 28days (OR 1.20, 95% CI 1.03, 1.39) were independent predictors of GDM, while mean temperatures were not. In pregnant women, rising environmental temperature in the 3-4weeks prior to glucose tolerance testing may be associated with beta cell dysfunction and an increased risk of GDM.

Plasma Metabolomics Reveal Novel Metabolites in Early Pregnancy in Association with Gestational Diabetes Risk

Although metabolomics may shed light on the pathophysiology of glucose metabolism in pregnancy, systematic studies on their roles in the development of gestational diabetes (GDM) are sparse. We aimed to prospectively investigated metabolomics (both targeted and non-targeted) and GDM risk in a matched case-control study of 107 GDM and 214 non-GDM women in a multi-racial cohort. GDM diagnosis was based on Carpenter and Coustan Criteria. Twenty-two amino acids were quantified using plasma collected at gestational weeks (GW) 10-14, 15-26, 23-31, and 33-39. In addition, 331 primary metabolites were quantified by GC-TOF-MS as a part of our non-targeted approach. Adjusted odds ratios (aORs) of GDM related to metabolites (in quartiles (Q)) were estimated using conditional logistic regression after adjusting for major GDM risk factors including BMI. The present report focuses on findings using blood samples in early pregnancy 10-14GW. Alanine in GW 10-14were higher in GDM women than controls (mean: 30.5 vs. 27.6 umol/dl) and were positively related to GDM risk; aORs across increasing Qs were 1.00, 1.69, 2.86, 3.05, (P for trend =0.020). By contrast, asparigine and glycine were significantly lower in GDM women, and were inversely related to GDM risk; aORs across increasing Qs were 1.00, 0.92, 0.74, and 0.48 (P for trend = 0.045) for asparagine and 1.00, 0.42, 0.36, and 0.24 (P &amp;lt;0.001) for glycine. In addition, among primary metabolites from the non-targeted approach, isocitric acid levels were positively related to GDM risk; aORs across increasing Qs were 1.00, 1.30, 1.04, 2.32 (P for trend = 0.002). Furthermore, two unknown metabolites were strongly and inversely associated with GDM risk (aORs were 1.00, 0.52, 0.18, 0.11, and 1.00, 0.33, 0.12, 0.respectively; both P &amp;lt; 10-4). Conclusion: Our study revealed several novel metabolites that may be implicated in the early pathogenesis of GDM, which might provide new etiological insight into the development of GDM. Disclosure C. Zhang: None. Y. Feng: None. O. Fiehn: None. M.Y. Tsai: None. Y. Zhu: None. P. Albert: None. L. Liang: None.

Low dietary fiber intake increases Collinsella abundance in the gut microbiota of overweight and obese pregnant women

ABSTRACTThe gut microbiota contributes to the regulation of glucose metabolism in pregnancy. Abundance of the genus Collinsella is positively correlated with circulating insulin; however, it is unclear what determines Collinsella abundance. This study aims to validate the correlation between Collinsella and insulin and to elucidate if macronutrient intake alters Collinsella abundance and gut microbiota composition.Gut microbiota profiles were assessed by 16S rRNA sequencing in 57 overweight and 73 obese pregnant women from the SPRING (Study of PRobiotics IN Gestational diabetes) trial at 16 weeks gestation and correlated with metabolic hormone levels and macronutrient intake. Gut microbiota composition in the top and bottom 10% of dietary fiber intake was evaluated through network analysis.Collinsella abundance correlated positively with circulating insulin (rho = 0.30, p = 0.0006), independent of maternal BMI, but negatively with dietary fiber intake (rho = −0.20, p = 0.025) in this cohort. Low dietary fiber intake was associated with a gut microbiota favoring lactate fermentation while high fiber intake promotes short-chain fatty acid-producing bacteria.Low dietary fiber may enable overgrowth of Collinsella and alter the overall fermentation pattern in gut microbiota. This suggests that dietary choices during pregnancy can modify the nutritional ecology of the gut microbiota, with potential deleterious effects on the metabolic and inflammatory health of the host.Trial registration: ANZCTR 12611001208998, registered 23/11/2011