Epigenetic Markers to Predict Conversion From Gestational Diabetes to Type 2 Diabetes

J Clin Endocrinol Metab. 2016 Jun;101(6):2396-404. doi: 10.1210/jc.2015-4206. Epub 2016 Apr 5.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • DNA Methylation
  • Diabetes Mellitus, Type 2 / diagnosis*
  • Diabetes Mellitus, Type 2 / genetics
  • Diabetes, Gestational / genetics*
  • Disease Progression
  • Epigenesis, Genetic*
  • Female
  • Genetic Markers
  • Histones / genetics*
  • Humans
  • Middle Aged
  • Pregnancy

Substances

  • Genetic Markers
  • Histones