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Intergenerational Programming of Diabesity in Offspring of Women With Gestational Diabetes Mellitus

Kem Hospital, Pune, India · 2014
ClinicalTrials.gov · Datasets · License: Public Domain · 2014
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epigeneticsgestational-diabetes
India is one of the diabetes capitals in the world. Indians are susceptible to develop diabetes at a younger age and at a lower BMI compared to Europeans. Current prevention strategies focus on reducing risk in those with the established disease or risk factors. The Developmental Origins of Health and Disease (DOHaD) hypothesis suggests that chronic non-communicable diseases (NCDs) are programmed by disturbances in maternal and fetal undernutrition. This offers an alternative primordial prevention strategy to reduce NCDs in future generations by improving health and nutrition of young women. Previous work in the Diabetes Unit, KEM Hospital, Pune has described the role of maternal micronutrients affecting 1-Carbon metabolism in the fetal programming of diabesity. In this application, the investigators offer to study other pathways of fetal programming i.e. maternal hyperglycemia and gestational diabetes mellitus (GDM) using an 'OMICs' approach. It is believed that epigenetic changes may be the main driver of programming. The investigators hypothesize that offspring of diabetic mothers will have different epigenetic signatures in cord blood and placenta compared to offspring of non-diabetic mothers. The investigators propose to study the effect of gestational hyperglycemia on newborn epigenetic signatures using the most appropriate technologies available and associate them with the underlying genotype. This will be performed on cord blood of 150 offspring of women with GDM and compared with a similar number of offspring of non-diabetic mothers recruited at Pune. The differentially methylated regions (DMRs) identified will then be validated by pyrosequencing in \~300 stored GDM cord blood samples in Pune. The investigators from Pune will also validate these markers in 200 newly recruited offspring of GDM and 200 controls from a different cohort in Punjab which has a different diet and lifestyle. The DMRs will also be validated in placental samples from both Pune and Pu
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