Size at birth, postnatal weight gain, and adult risk for type 2 diabetes may reflect environmental exposures during developmental plasticity and may be mediated by epigenetics. Both low birth weight (BW), as a marker of fetal growth restraint, and high birth weight (BW), especially after gestational diabetes mellitus (GDM), have been linked to increased risk of adult type 2 diabetes. We assessed DNA methylation patterns using a bead chip in cord blood samples from infants of mothers with GDM (group 1) and infants with prenatal growth restraint indicated by rapid postnatal catch-up growth (group 2), compared with infants with normal postnatal growth (group 3). Seventy-five CpG loci were differentially methylated in groups 1 and 2 compared with the controls (group 3), representing 72 genes, many relevant to growth and diabetes. In replication studies using similar methodology, many of these differentially methylated regions were associated with levels of maternal glucose exposure below that defined by GDM [the Hyperglycemia and Adverse Pregnancy Outcome (HAPO) study] or were identified as changes observed after randomized periconceptional nutritional supplementation in a Gambian cohort characterized by maternal deprivation. These studies provide support for the concept that similar epigenetic modifications may underpin different prenatal exposures and potentially increase long-term risk for diseases such as type 2 diabetes.

Ancillary Datasets S1 and S2 Quilter et al. FASEB J 2014Sample analysis was carried out using the Methylation Module of the Illumina Genome Studio software for Ancillary Datasets: S1: results have a cut off values of ± 10% delta beta at a P value < 0.001 equivalent to a DiffScore of >30 or <-30 on the Illumina significance threshold scale.S2: results have a cut off values of ± 5-10% delta beta at a P value < 0.001 equivalent to a DiffScore of >30 or <-30 on the Illumina significance threshold scale.Ancillary Dataset S1 and S2 Quilter et al. FASEB 2014.doc