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

Abstract

BackgroundGestational 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.MethodsSecond 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.ResultsGDM 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).ConclusionsThese 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.

Postpartum Circulating Cell-Free Insulin DNA Levels Are Higher in Women with Previous Gestational Diabetes Mellitus Who Develop Type 2 Diabetes in Later Life

“…We did not observe any increase in unmethylated insulin cfDNA copies in women who progressed to T2DM during the study. This is in line with the gestational islet β -cell death measurements made by Kenna et al [24], suggesting that there is no islet β -cell death during pregnancy or immediately postpartum but that the overall effect of GDM-related stressors affects nonislet tissues that possibly induce a series of inflammatory events resulting in reduced β -cell function and progression to T2DM later in life.…”

“…This is the first report analyzing postpartum insulin cfDNA in a longitudinal study cohort of women with GDM ( n = 97). In an earlier cross-sectional study, 22 women with GDM were compared with 14 non-GDM pregnant women with an aim to assess the death of pancreatic β -cell (increased unmethylated insulin cfDNA) in the women with GDM [24]. These investigators did not observe any increased islet β -cell death in mothers with GDM compared to those without GDM.…”

Circulating unmethylated insulin DNA as a potential non-invasive biomarker of beta cell death in type 1 Diabetes: a review and future prospect

“…We believe that with technological advances, more target genes of interest can be explored and readily combined into panels to optimize the sensitivity and specificity of these assays. Another recent study reported a negative relation between the onset of gestational diabetes mellitus (GDM) and β cell loss by using the detection of unmethylated INS DNA [ 31 ]. Interestingly, the levels of unmethylated INS DNA were significantly decreased in women with GDM comparing to women with normal pregnancy, women at postpartum, and non-pregnant women [ 31 ].…”

“…Another recent study reported a negative relation between the onset of gestational diabetes mellitus (GDM) and β cell loss by using the detection of unmethylated INS DNA [ 31 ]. Interestingly, the levels of unmethylated INS DNA were significantly decreased in women with GDM comparing to women with normal pregnancy, women at postpartum, and non-pregnant women [ 31 ]. The study told us that the detection of unmethylated INS DNA may provide more detailed information about the natural history and heterogeneity of T1D, which is crucial to illustrate the etiology of T1D [ 32 ].…”

Genetic association between angiotensin converting enzyme gene in Saudi obese women established gestational diabetes; Non-replication of case-control studies in insertion and deletion polymorphism

“…6 A significant risk factor for GDM has been documented as maternal health, macrosomia and cesarean delivery. 7 Born neonates to GDM mother will have risk of low blood glucose other complications such as jaundice, pre-eclampsia, polycythemia and respiratory related syndromes. 8 All types of diabetes such as T1DM, T2DM, GDM and specific types of diabetes due to other causes has genetic com--ponent.…”