A defining feature of mammals is the development in utero of the fetus supported by the constant flow of nutrients from the mother (John and Hemberger, 2012). Poor growth in utero combined with rapid post natal catch up growth is known to predispose to the development of metabolic diseases in adult humans, including type 2 diabetes. A significant proportion of human low birth weight infants exhibit elevated placental expression of the imprinted PLECKSTRIN HOMOLOGY-LIKE DOMAIN, FAMILY A, MEMBER 2 (PHLDA2/IPL/TSSC3) gene (McMinn et al., 2006). We have engineered this specific alteration in a mouse model system and found that elevated expression of Phlda2 drives severe placental defects alongside asymmetrical fetal growth restriction (Tunster et al., 2010). The low birth weight offspring rapidly catch up growth with their littermates but develop glucose intolerance and show increased adiposity as adults. Using another genetic model, we are able to rescue both fetal growth restriction and glucose intolerance thus assigning the adult phenotypes to the in utero growth restricting properties of Phlda2. We are also able to demonstrate that Phlda2 is a nutrient responsive gene in the placenta. These data support the idea that factors manipulating epigenetic processes early in life can influence the aging process. Furthermore, our data suggest that low birth weight human infants with high PHLDA2 expression may be predisposed to develop type 2 diabetes and other diseases linked to fetal programming.