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>