Data on offspring of women with diet-treated gestational diabetes compared with offspring from the background population.

<p>Data are mean (SD) or proportions (n) if not otherwise stated. For some of the variables, numbers are changing due to missing data. Bold P<0.05. Gestational diabetes (GDM).</p>*<p>Analyses of differences between means, medians and proportions were by Student’s t-test, Mann-Whitney, Chi² or Fishers exact test, respectively.</p>†<p>Data are given as median (25–75% percentiles), as data were not normally distributed.</p>‡<p>Defined as presence of either: placental abruption, shoulder dystocia, 5-min Apgar<7, jaundice or assisted ventilation >60 minutes.</p><p>•Defined as the re-standardized mean test score of the four cognitive subtests.</p

Global cognitive score in offspring of women with diet-treated GDM (n = 153) compared with offspring from the background population (n = 118).

<p>Linear regression analyses giving data on global cognitive score in the offspring. Test-score mean difference is given as regression coefficient (ß) with 95% confidence interval (CI) and P value.</p><p>Bold P<0.05.</p><p>Model 1: Maternal age at delivery, parity, smoking during pregnancy, gender, offspring age.</p><p>Model 2: Birth weight, gestational age.</p><p>Model 3: Perinatal complications.</p><p>Model 4: Maternal pre-pregnancy BMI≥25.</p><p>Model 5: Family social class.</p><p>Model 6: Parental educational level.</p><p>Full model: All covariates from model 1–6.</p

Evaluation of potential effect-modification by mode of delivery on the association between redemption of antibiotics within the first two years of life and subsequent onset of childhood type 1 diabetes (2 to 14 years, both included).

<p>Evaluation of potential effect-modification by mode of delivery on the association between redemption of antibiotics within the first two years of life and subsequent onset of childhood type 1 diabetes (2 to 14 years, both included).</p

Flow chart describing subjects in the study.

<p>GDM: gestational diabetes mellitus *Reasons for lost to follow-up: Offspring of women with diet-treated GDM: 50% did not respond, 26% refused to participate, 9% had emigrated, 6% had died, 4% did not show up and 5% had other reasons. Offspring from the background population: 42% did not respond, 33% refused to participate, 9% had emigrated, 4% had died, 8% did not show up and 4% had other reasons. **Included offspring of women with GDM: 61% (153/252) of all Nordic offspring, 52% (153/295) of eligible offspring. ***Included offspring of women from the background population: 52% (118/225) of all Nordic offspring, 46% (118/256) of eligible offspring.</p

Redemption of antibiotics within the first two years of life.

<p>Included are all children born in Denmark 1997 to 2010, who by their two years birthday were alive and had not emigrated or been diagnosed with type 1 diabetes (n = 858,201). The proportion of children redeeming broad-spectrum and narrow-spectrum antibiotics, respectively, include also children who had redeemed both broad- and narrow-spectrum antibiotics within the first two years of life.</p

Background characteristics for singleton children born 1997 to 2010 and their parents^a.

<p>Background characteristics for singleton children born 1997 to 2010 and their parents<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0161654#t001fn001" target="_blank">^a</a>.</p

Associations between redemption of antibiotics within the first two years of life and subsequent onset of childhood type 1 diabetes (2 to 14 years, both included).

<p>Associations between redemption of antibiotics within the first two years of life and subsequent onset of childhood type 1 diabetes (2 to 14 years, both included).</p

DNA methylation and gene expression of <i>TXNIP</i> in adult offspring of women with diabetes in pregnancy

<div><p>Background</p><p>Fetal exposure to maternal diabetes increases the risk of type 2 diabetes (T2DM), possibly mediated by epigenetic mechanisms. Low blood <i>TXNIP</i> DNA methylation has been associated with elevated glucose levels and risk of T2DM, and increased skeletal muscle <i>TXNIP</i> gene expression was reported in subjects with impaired glucose metabolism or T2DM. Subcutaneous adipose tissue (SAT) and skeletal muscle play a key role in the control of whole body glucose metabolism and insulin action. The extent to which <i>TXNIP</i> DNA methylation levels are decreased and/or gene expression levels increased in SAT or skeletal muscle of a developmentally programmed at-risk population is unknown.</p><p>Objective and methods</p><p>The objective of this study was to investigate <i>TXNIP</i> DNA methylation and gene expression in SAT and skeletal muscle, and DNA methylation in blood, from adult offspring of women with gestational diabetes (O-GDM, n = 82) or type 1 diabetes (O-T1DM, n = 67) in pregnancy compared with offspring of women from the background population (O-BP, n = 57).</p><p>Results</p><p>SAT <i>TXNIP</i> DNA methylation was increased (p = 0.032) and gene expression decreased (p = 0.001) in O-GDM, but these differences were attenuated after adjustment for confounders. Neither blood/muscle <i>TXNIP</i> DNA methylation nor muscle gene expression differed between groups.</p><p>Conclusion</p><p>We found no evidence of decreased <i>TXNIP</i> DNA methylation or increased gene expression in metabolic target tissues of offspring exposed to maternal diabetes. Further studies are needed to confirm and understand the paradoxical SAT <i>TXNIP</i> DNA methylation and gene expression changes in O-GDM subjects.</p></div

Baseline clinical characteristics in adult offspring of women with gestational diabetes (O-GDM) or type 1 diabetes (O-T1DM) compared to offspring of women from the background population (O-BP).

<p>Baseline clinical characteristics in adult offspring of women with gestational diabetes (O-GDM) or type 1 diabetes (O-T1DM) compared to offspring of women from the background population (O-BP).</p

Correlations between <i>TXNIP</i> DNA methylation and gene expression and offspring markers of metabolic disease.

<p>Correlations between <i>TXNIP</i> DNA methylation and gene expression and offspring markers of metabolic disease.</p