β-Cell death is decreased in women with gestational diabetes mellitus

Background: Gestational diabetes mellitus (GDM) affects approximately 7-17 % of all pregnancies and has been recognized as a significant risk factor to neonatal and maternal health. Postpartum, GDM significantly increases the likelihood of developing type 2 diabetes (T2D). While it is well established that insulin resistance and impaired beta-cell function contribute to GDM development, the role of active beta-cell loss remains unknown. Differentially methylated circulating free DNA (cfDNA) is a minimally invasive biomarker of beta-cell loss in type 1 diabetes mellitus. Here we use cfDNA to examine the levels of A-cell death in women with GDM. Methods: Second to third-trimester pregnant women with GDM were compared with women with normal pregnancy (PRG), women at postpartum (PP), and non-pregnant (NP) women. Fasting glucose levels, insulin, and C-peptide levels were measured. Serum samples were collected and cfDNA purified and bisulfite treated. Methylation-sensitive probes capable of differentiating between beta-cell-derived DNA (demethylated) and non--cell-derived DNA (methylated) were used to measure the presence of beta-cell loss in the blood. Results: GDM was associated with elevated fasting glucose levels (GDM = 185.9 +/- 5.0 mg/dL) and reduced fasting insulin and c-peptide levels when compared with NP group. Interestingly, beta-cell derived insulin DNA levels were significantly lower in women with GDM when compared with PRG, NP, and PP groups (demethylation index: PRG = 7.74 x 10(-3) +/- 3.09 x 10(-3), GDM = 1.01 x 10(-3) +/- 5.86 x 10(-4), p < 0.04; NP = 4.53 x 10(-3) +/- 1.62 x 10(-3), PP = 3.24 x 10(-3) +/- 1.78 x 10(-3)). Conclusions: These results demonstrate that beta-cell death is reduced in women with GDM. This reduction is associated with impaired insulin production and hyperglycemia, suggesting that beta-cell death does not contribute to GDM during the 2nd and 3rd trimester of pregnancy.