Additional file 1: Table S1. of 36 h fasting of young men influences adipose tissue DNA methylation of LEP and ADIPOQ in a birth weight-dependent manner

Primers used in amplification of the specific DNA sequences of the ADIPOQ and LEP promoter regions. Table S2. DNA methylation (%) of CpG sites in the LEP promoter in adipose tissue. Table S3. DNA methylation (%) of CpG sites in the ADIPOQ promoter in adipose tissue. Table S4. DNA methylation (%) of CpG sites in the LEP promoter in adipose tissue. Table S5. DNA methylation (%) of CpG sites in the ADIPOQ promoter in adipose tissue. (DOCX 34 kb

Additional file 4: Table S2. of DNA methylation and gene expression of HIF3A: cross-tissue validation and associations with BMI and insulin resistance

Associations between HIF3A DNA methylation levels in blood and subcutaneous adipose tissue. (PDF 175 kb

Additional file 3: Figure S2. of DNA methylation and gene expression of HIF3A: cross-tissue validation and associations with BMI and insulin resistance

Correlation between HIF3A DNA methylation levels at CpG sites 1 to 4 in subcutaneous adipose tissue. (PDF 126 kb

CpG sites analyzed in the <i>PPARGC1A</i> promoter.

<p>The CpG sites investigated are marked with a perpendicular line.</p

Clinical characteristics of the FDR group (n = 124) stratified according to glucose tolerance status.

<p>Data are mean ± SD. Significant differences between NGT and IFG/IGT at *<i>P</i><0.05. **<i>P</i><0.001. Significant differences between NGT and T2D at ⁺<i>P</i><0.05, ⁺⁺<i>P</i><0.001. Significant differences between IFG/IGT and T2D at ^§<i>P</i><0.05, ^§§<i>P</i><0.001. All parameters except age and BMI were analyzed with unpaired non-parametric tests due to lack of normal distribution. Indices of insulin sensitivity and insulin secretion were calculated as described in subjects and methods. BMI, body mass index; CIR, corrected insulin response; HOMA-β, homeostatic model assessment of β-cell function; HOMA-IR, homeostatic model assessment of insulin resistance; IFG, impaired fasting glycemia; IGT, impaired glucose tolerance; NGT, normal glucose tolerance; OGTT, oral glucose tolerance test; T2D, type 2 diabetes.</p

Skeletal muscle gene expression of <i>PPARGC1A</i>.

<p>Participants are stratified according to glucose tolerance status (NGT, IFG/IGT, T2D). Data are mean±SE.</p

Correlation between average skeletal muscle DNA methylation and gene expression of <i>PPARGC1A</i>.

<p>Methylation is show in percentage and gene expression in arbitrary units (AU). β = 0.013 (−0.034;0.059), <i>P = </i>0.59, adjusted for age, gender, BMI, glucose tolerance and family pedigree. Unadjusted (Spearman’s correlation): ρ 0.22, <i>P</i> = 0.04.methylation at CpG site −260 in the <i>PPARGC1A</i> promoter was 0% in 98 individuals and 4–10% in 11 individuals (4 with T2D and 7 with NGT). The DNA methylation at CpG site −260 was not different among T2D (1.1±1.7) compared to NGT subjects (0.74±2.3), and there were no significant associations between DNA methylation and whole body insulin sensitivity, gene expression or any other clinical parameter (data not shown).</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