Figure 1.

The cycle of metabolic disease epidemics. Fetal overnutrition due to GDM and/or maternal obesity leads to epigenetic changes in the exposed offspring. As an example, the box plot diagrams on top show the significantly different distribution of placenta MEST methylation values in newborns of mothers with dietetically treated D-GDM and insulin-treated I-GDM, compared with newborns of mothers without GDM. MEST hypomethylation may foreshadow diet-induced obesity. Similarly, epigenetic changes in numerous other genes may increase the lifelong metabolic disease susceptibility and, thus, the likelihood for a new generation of mothers with GDM and/or obesity, feeding the vicious cycle. Consistent with the decreasing plasticity of the epigenome, the effect of possible interventions to break the cycle can be expected to be larger in the periconceptional and prenatal period than after birth, during infancy and in adulthood.