Epigenetic markers to predict conversion from gestational diabetes to type 2 diabetes

Abstract

Context: Lifestyle factors mediate epigenetic changes that can cause chronic diseases. Although animal and laboratory studies link epigenetic changes to diabetes, epigenetic information in women with gestational diabetes (GDM) and type 2 diabetes is lacking. Objective: This study sought to measure epigenetic markers across pregnancy and early postpartum and identify markers that could be used as predictors for conversion from GDM to type 2 diabetes. Design: Global histone H3 dimethylation was measured in white blood cells at three time points: 30 wk gestation, 8-10 wk postpartum, and 20 wk postpartum, from four groups of women with and without diabetes. Setting and Participants: A total of 39 participants (six to nine in each group) were recruited including: nondiabetic women; women with GDM who developed postpartum type 2 diabetes; women with GDM without postpartum type 2 diabetes; and women with type 2 diabetes. Main Outcome Measure: Percentages of dimethylation of H3 histones relative to total H3 histone methylation were compared between diabetic/nondiabetic groups using appropriate comparative statistics. Results: H3K27 dimethylation was 50-60% lower at 8-10 and 20 wk postpartum in women with GDM who developed type 2 diabetes, compared with nondiabetic women. H3K4 dimethylation was 75% lower at 8-10 wk postpartum in women with GDM who subsequently developed type 2 diabetes compared with women who had GDM who did not. Conclusions: The percentage of dimethylation of histones H3K27 and H3K4 varied with diabetic state and has the potential as a predictive tool to identify women who will convert from GDM to type 2 diabetes.