http://repub.eur.nl/res/aut/7591/ List of Publications en http://repub.eur.nl/static-eur/img/logo.png http://repub.eur.nl http://repub.eur.nl/res/pub/33052/ 2010-10-01T00:00:00Z OBJECTIVE - Early developmental adaptations in response to undernutrition may play an essential role in susceptibility to type 2 diabetes, particularly for those experiencing a "mismatched rich nutritional environment" in later life. We examined the associations of exposure to the Chinese famine (1959-1961) during fetal life and childhood with the risk of hyperglycemia and type 2 diabetes in adulthood. RESEARCH DESIGN AND METHODS - We used the data for 7,874 rural adults born between 1954 and 1964 in selected communities from the cross-sectional 2002 China National Nutrition and Health Survey. Hyperglycemia was defined as fasting plasma glucose ≥6.1 mmol/l and/or 2-h plasma glucose ≥7.8 mmol/l and/or a previous clinical diagnosis of type 2 diabetes. RESULTS - Prevalences of hyperglycemia among adults in nonexposed, fetal exposed, early-childhood, mid-childhood, and late-childhood exposed cohorts were 2.4%, 5.7%, 3.9%, 3.4%, and 5.9%, respectively. In severely affected famine areas, fetal-exposed subjects had an increased risk of hyperglycemia compared with nonexposed subjects (odds ratio = 3.92; 95% CI: 1.64 -9.39; P = 0.002); this difference was not observed in less severely affected famine areas (odds ratio = 0.57; 95% CI: 0.25-1.31; P = 0.185). The odds ratios were significantly different between groups from the severe and less severe famine areas (P for interaction = 0.001). In severely affected famine areas, fetalexposed subjects who followed an affluent/Western dietary pattern (odds ratios = 7.63; 95% CI: 2.41-24.1; P = 0.0005) or who had a higher economic status in later life experienced a substantially elevated risk of hyperglycemia (odds ratios = 6.20; 95% CI: 2.08 -18.5; P = 0.001). CONCLUSIONS - Fetal exposure to the severe Chinese famine increases the risk of hyperglycemia in adulthood. This association appears to be exacerbated by a nutritionally rich environment in later life. http://repub.eur.nl/res/pub/2541/ 1997-01-01T00:00:00Z We previously demonstrated that the zinc finger transcription factors GATA-2 and GATA-3 are expressed in trophoblast giant cells and that they regulate transcription from the mouse placental lactogen I gene promoter in a transfected trophoblast cell line. We present evidence here that both of these factors regulate transcription of the placental lactogen I gene, as well as the related proliferin gene, in trophoblast giant cells in vivo. Placentas lacking GATA-3 accumulate placental lactogen I and proliferin mRNAs to a level 50% below that reached in the wild-type placenta. Mutation of the GATA-2 gene had a similar effect on placental lactogen I expression, but led to a markedly greater reduction (5- to 6-fold) in proliferin gene expression. Placentas lacking GATA-2 secrete significantly less angiogenic activity than wild-type placentas as measured in an endothelial cell migration assay, consistent with a reduction in expression of the angiogenic hormone proliferin. Furthermore, within the same uterus the decidual tissue adjacent to mutant placentas displays markedly reduced neovascularization compared to the decidual tissue next to wild-type placentas. These results indicate that GATA-2 and GATA-3 are important in vivo regulators of trophoblast-specific gene expression and placental function, and reveal a difference in the effect of these two factors in regulating the synthesis of related placental hormones.