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Epigenetics and gestational diabetes – a review of epigenetic epidemiology studies and their use to explore epigenetic mediation and improve prediction

Research output: Contribution to journalReview article

Original languageEnglish
JournalDiabetologia
DateAccepted/In press - 22 Jul 2019

Abstract

Epigenetics encapsulates a group of molecular mechanisms including DNA methylation, histone modification and microRNAs (miRNAs). Gestational diabetes (GD) increases the risk of adverse perinatal outcomes and is associated with future offspring risk of obesity and type 2 diabetes (T2D). It has been hypothesised that epigenetic mechanisms mediate an effect of GD on offspring adiposity and T2D and this could provide a modifiable mechanism to reduce T2D in the next generation. Evidence for this hypothesis is lacking. Epigenetic epidemiology could also contribute to reducing T2D by identifying biomarkers that accurately predict risk of GD and its associated future adverse outcomes.
We reviewed published human studies that explored associations between any of maternal GD, T2D, gestational fasting or post-load glucose and any epigenetic marker (DNA methylation, histone modification or miRNA). Of the 81 relevant studies we identified, most focused on the potential role of epigenetic mechanisms in mediating intrauterine effects of GD on offspring outcomes. Studies were small (median total number of participants =58; median GD cases =27) and mostly did not attempt replication. The most common epigenetic measure analysed was DNA methylation. Most studies that aimed to explore epigenetic mediation examined associations of in utero exposure to GD with offspring cord- or infant-blood/placenta DNA methylation. Exploration of any causal effect, or effect on downstream offspring outcomes, was lacking.
There is a need for more robust methods to explore the role of epigenetic mechanisms as possible mediators of effects of exposure to GD on future risk of obesity and T2D. Research to identify epigenetic biomarkers to improve identification of women at risk of GD and its associated adverse (maternal and offspring) outcomes is currently rare but could contribute to future tools for accurate risk stratification.

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