Project description:AIMS:Epigenetic regulators, including microRNAs (miRNAs), are implicated in type 2 diabetes, but evidence linking circulating miRNAs in pregnancy and risk of gestational diabetes (GDM) is sparse. Potential modifiers, including pre-pregnancy overweight/obesity and offspring sex, are unexamined. We hypothesized that circulating levels of early-mid-pregnancy (range 7-23weeks of gestation) candidate miRNAs are related to subsequent development of GDM. We also hypothesized that miRNA-GDM associations might vary by pre-pregnancy body-mass index (ppBMI) or offspring sex. METHODS:In a case-control analysis (36GDM cases/80 controls) from the Omega study, a prospective cohort study of pregnancy complications, we measured early-mid-pregnancy plasma levels of 10miRNAs chosen for potential roles in pregnancy course and complications (miR-126-3p, -155-5p, -21-3p, -146b-5p, -210-3p, -222-3p, -223-3p, -517-5p, -518a-3p, and 29a-3p) using qRT-PCR. Logistic regression models adjusted for gestational age at blood draw (GA) were fit to compare circulating miRNAs between cases and controls. We repeated analyses among overweight/obese (ppBMI?25kg/m2) or lean (ppBMI<25kg/m2) women, and women with male or female offspring separately. RESULTS:Mean age was 34.3years (cases) and 32.9years (controls). GA-adjusted miR-155-5p (?=0.260/p=0.028) and -21-3p (?=0.316/p=0.005) levels were positively associated with GDM. MiR-146b-5p (?=0.266/p=0.068) and miR-517-5p (?=0.196/p=0.074) were borderline. Associations of miR-21-3p and miR-210-3p with GDM were observed among overweight/obese but not lean women. Associations of six miRNAs (miR-155-5p, -21-3p, -146b-5p, -223-3p, -517-5p, and -29a-3p) with GDM were present only among women carrying male fetuses (all p<0.05). CONCLUSIONS:Circulating early-mid-pregnancy miRNAs are associated with GDM, particularly among women who are overweight/obese pre-pregnancy or pregnant with male offspring. This area has potential to clarify mechanisms underlying GDM pathogenesis and identify at-risk mothers earlier in pregnancy.

Project description:ObjectiveTo assess patterns and predictors of postpartum diabetes screening in a commercially insured, geographically and sociodemographically diverse sample of women with gestational diabetes mellitus.MethodsUsing commercial insurance claims (2000-2012) from all 50 states, we conducted a retrospective cohort study in 447,556 women with at least one delivery and continuous enrollment 1 year before and after delivery. We identified women with a gestational diabetes mellitus pregnancy and examined postpartum diabetes screening type and timing and performed logistic regression to identify screening predictors.ResultsGestational diabetes mellitus was diagnosed in 32,253 (7.2%) women during the study timeframe. Three fourths received no screening within 1 year postpartum. Rates of recommended 75-g oral glucose tolerance testing within 6-12 weeks were low but increased over time (27 [2%] in 2001 compared with 249 [7%] in 2011, adjusted odds ratio [OR] 3.1, 95% confidence interval [CI] 2.0-47). Among women screened, those in the Northeast (19%) and South (18%) were least likely to receive a 75-g oral glucose tolerance test within 0-12 weeks (adjusted OR 0.4 for each, CI 0.4-0.5) compared with the West (36%). Asian women were most likely to receive any screening (18%; adjusted OR 1.5, CI 1.3-1.6) compared with white women (12%). Black women were most likely to receive hemoglobin A1c (21%; adjusted OR 2.0, CI 1.3-3.2) compared with white women (11%). Antepartum antiglycemic medication (21%; adjusted OR 2.1, CI 2.0-2.3) or visit to a nutritionist-diabetes educator (19%; adjusted OR 1.6, CI 1.4-1.7) or endocrinologist (23%; adjusted OR 1.7, CI 1.6-1.9) predicted screening within 12 weeks postpartum.ConclusionPostpartum diabetes screening remains widely underused among commercially insured women with gestational diabetes mellitus. Differences in screening by geography, race, and antepartum care can inform health system and public health interventions to increase diabetes detection in this high-risk population.

Project description:Data on the temporal dynamics of human placental gene expression is scarce. We have completed the first whole-genome profiling of human placental gene expression dynamics (GeneChips, Affymetrix®) from early to mid- gestation (10 samples; gestational weeks 5 to 18) and report 154 genes with considerable change in transcript levels (FDR P<0.1). Functional enrichment analysis revealed >200 GO categories that are statistically over-represented among 105 genes with dynamically increasing transcript levels. Analysis in an extended sample (n=43; gestational weeks 5 to 41) conformed a highly significant (FDR P<0.05) expressional peak in mid-gestation placenta for ten genes: BMP5, CCNG2, CDH11, FST, GATM, GPR183, ITGBL1, PLAGL1, SLC16A10, STC1. A central hypothesis of our study states that the aberrant expression of genes characteristic to mid-gestation placenta may contribute to affected fetal growth, maternal preeclampsia (PE) or gestational diabetes (GD). The gene STC1 coding for Stanniocalcin 1 (STC1) was identified with a sharp placental expressional peak in mid-gestation, increased mRNA levels at term and significantly elevated STC1 protein levels in post-partum maternal plasma in all pregnancy complications. The highest STC1 levels were identified in women, who developed simultaneously PE and delivered an SGA baby (median 731 vs 418 pg/ml in controls; P=0.001). CCNG2 and LYPD6 exhibited significantly increased placental mRNA expression and enhanced intensity of immunohistochemistry staining in placental sections all studied in GD and PE cases. Aberrant expression of mid-gestation specific genes in pregnancy complications at term indicates the importance of the fine-scale tuning of the temporal dynamics of transcription regulation in placenta. Observed significantly elevated plasma STC1 in complicated pregnancies warrants further investigations of its potential as a biomarker. Interestingly, a majority of genes with high expression in mid-gestation placenta have also been implicated in adult complex disease. This observation promotes a recently opened discussion on the role of placenta in developmental programming.

Project description:Despite the importance of placenta in mediating rapid physiological changes in pregnancy, data on temporal dynamics of placental gene expression are limited. We completed the first transcriptome profiling of human placental gene expression dynamics (GeneChips, Affymetrix®; ~47,000 transcripts) from early to mid-gestation (n = 10; gestational weeks 5-18) and report 154 genes with significant transcriptional changes (ANOVA, FDR P<0.1). TaqMan RT-qPCR analysis (n = 43; gestational weeks 5-41) confirmed a significant (ANOVA and t-test, FDR P<0.05) mid-gestational peak of placental gene expression for BMP5, CCNG2, CDH11, FST, GATM, GPR183, ITGBL1, PLAGL1, SLC16A10 and STC1, followed by sharp decrease in mRNA levels at term (t-test, FDR P<0.05). We hypothesized that normal course of late pregnancy may be affected when genes characteristic to mid-gestation placenta remain highly expressed until term, and analyzed their expression in term placentas from normal and complicated pregnancies [preeclampsia (PE), n = 12; gestational diabetes mellitus (GDM), n = 12; small- and large-for-gestational-age newborns (SGA, LGA), n = 12+12]. STC1 (stanniocalcin 1) exhibited increased mRNA levels in all studied complications, with the most significant effect in PE- and SGA-groups (t-test, FDR P<0.05). In post-partum maternal plasma, the highest STC1 hormone levels (ELISA, n = 129) were found in women who had developed PE and delivered a SGA newborn (median 731 vs 418 pg/ml in controls; ANCOVA, P = 0.00048). Significantly higher expression (t-test, FDR P<0.05) of CCNG2 and LYPD6 accompanied with enhanced immunostaining of the protein was detected in placental sections of PE and GDM cases (n = 15). Our study demonstrates the importance of temporal dynamics of placental transcriptional regulation across three trimesters of gestation. Interestingly, many genes with high expression in mid-gestation placenta have also been implicated in adult complex disease, promoting the discussion on the role of placenta in developmental programming. The discovery of elevated maternal plasma STC1 in pregnancy complications warrants further investigations of its potential as a biomarker.

Project description:Data on the temporal dynamics of human placental gene expression is scarce. We have completed the first whole-genome profiling of human placental gene expression dynamics (GeneChips, Affymetrix®) from early to mid- gestation (10 samples; gestational weeks 5 to 18) and report 154 genes with considerable change in transcript levels (FDR P<0.1). Functional enrichment analysis revealed >200 GO categories that are statistically over-represented among 105 genes with dynamically increasing transcript levels. Analysis in an extended sample (n=43; gestational weeks 5 to 41) conformed a highly significant (FDR P<0.05) expressional peak in mid-gestation placenta for ten genes: BMP5, CCNG2, CDH11, FST, GATM, GPR183, ITGBL1, PLAGL1, SLC16A10, STC1. A central hypothesis of our study states that the aberrant expression of genes characteristic to mid-gestation placenta may contribute to affected fetal growth, maternal preeclampsia (PE) or gestational diabetes (GD). The gene STC1 coding for Stanniocalcin 1 (STC1) was identified with a sharp placental expressional peak in mid-gestation, increased mRNA levels at term and significantly elevated STC1 protein levels in post-partum maternal plasma in all pregnancy complications. The highest STC1 levels were identified in women, who developed simultaneously PE and delivered an SGA baby (median 731 vs 418 pg/ml in controls; P=0.001). CCNG2 and LYPD6 exhibited significantly increased placental mRNA expression and enhanced intensity of immunohistochemistry staining in placental sections all studied in GD and PE cases. Aberrant expression of mid-gestation specific genes in pregnancy complications at term indicates the importance of the fine-scale tuning of the temporal dynamics of transcription regulation in placenta. Observed significantly elevated plasma STC1 in complicated pregnancies warrants further investigations of its potential as a biomarker. Interestingly, a majority of genes with high expression in mid-gestation placenta have also been implicated in adult complex disease. This observation promotes a recently opened discussion on the role of placenta in developmental programming. 4 samples; this submission is extension of our earlier study (accession GSE22490).

Dataset Information

Mid-Pregnancy Fructosamine Measurement-Predictive Value for Gestational Diabetes and Association with Postpartum Glycemic Indices.

Publications

Mid-Pregnancy Fructosamine Measurement-Predictive Value for Gestational Diabetes and Association with Postpartum Glycemic Indices.

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