title: β-Cell death is decreased in women with gestational diabetes mellitus.
abstract: 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 β-cell function contribute to GDM development, the role of active β-cell loss remains unknown. Differentially methylated circulating free DNA (cfDNA) is a minimally invasive biomarker of β-cell loss in type 1 diabetes mellitus. Here we use cfDNA to examine the levels of β-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 β-cell-derived DNA (demethylated) and non-β-cell-derived DNA (methylated) were used to measure the presence of β-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, β-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 × 10(-3) ± 3.09 × 10(-3), GDM = 1.01 × 10(-3) ± 5.86 × 10(-4), p < 0.04; NP = 4.53 × 10(-3) ± 1.62 × 10(-3), PP = 3.24 × 10(-3) ± 1.78 × 10(-3)).
  
  
  CONCLUSIONS
  These results demonstrate that β-cell death is reduced in women with GDM. This reduction is associated with impaired insulin production and hyperglycemia, suggesting that β-cell death does not contribute to GDM during the 2nd and 3rd trimester of pregnancy.
authors: Research Institute, Islet Biology, Winthrop-University Hospital, 101 Mineola Blvd. Rm. 4-39, Mineola, NY 11501 USA.
authors: Lauren A
authors: LA
authors: Kenna
authors: Research Institute, Islet Biology, Winthrop-University Hospital, 101 Mineola Blvd. Rm. 4-39, Mineola, NY 11501 USA.
authors: John A
authors: JA
authors: Olsen
authors: Research Institute, Islet Biology, Winthrop-University Hospital, 101 Mineola Blvd. Rm. 4-39, Mineola, NY 11501 USA.
authors: Michael G
authors: MG
authors: Spelios
authors: Division of Endocrinology, Diabetes & Metabolism, Winthrop-University Hospital, Mineola, NY USA ; Stony Brook University School of Medicine, Stony Brook, NY USA.
authors: Michael S
authors: MS
authors: Radin
authors: Research Institute, Islet Biology, Winthrop-University Hospital, 101 Mineola Blvd. Rm. 4-39, Mineola, NY 11501 USA ; Stony Brook University School of Medicine, Stony Brook, NY USA.
authors: Eitan M
authors: EM
authors: Akirav