Maternal diabetes, gestational diabetes and the role of epigenetics in their long term effects on offspring

There is a global epidemic of obesity and diabetes, and current efforts to curb the diabetes epidemic have had limited success. Epidemiological studies have highlighted increased risk of obesity, diabetes and cardiovascular complications in offspring exposed to maternal diabetes, and gestational diabetes increases the risk of diabetes in subsequent generations, thereby setting up a vicious cycle of “diabetes begetting diabetes”. This relationship between maternal hyperglycaemia and long-term health in the offspring is likely to become even more important with an increasing proportion of young woman being affected by diabetes, and the number of pregnancies complicated by hyperglycaemia continuing to rise. Animal models of gestational diabetes or maternal hyperglycaemia have highlighted long-term changes in the offspring with some instances of sex bias, including increased adiposity, insulin resistance, β-cell dysfunction, hypertension, as well as other structural and functional changes. Furthermore, several of these changes appear to be transmissible to later generations through the maternal line. Epigenetic changes play an important role in regulating gene expression, especially during early development. Recent studies have identified a number of epigenetic modifications in the offspring associated with maternal hyperglycaemia. In this review, we provide an overview of the epidemiological evidence linking maternal hyperglycaemia with adverse long-term outcome in the offspring, as well as of some of the studies that explore the underlying epigenetic mechanisms. A better understanding of the pathways involved may provide novel approaches for combating this global epidemic.