Glucose Metabolism in Adults Prenatally Exposed to Diabetic Pollutants

Country/Countries:
,

Principal Investigator:
Philippe Grandjean, Adjunct Professor of Environmental Health

Dates of Research:
February 1, 2013 — October 31, 2017

Description:

To assess the role of environmental chemicals in the etiology of type 2 diabetes development, a birth cohort of 1022 subjects born in 1986-1987 will be examined in the Faroe Islands, where an unusually wide range of exposures to environmental chemicals has been documented. Cohort members, who are now 27 years, will be invited for clinical examination, including oral glucose tolerance test, to assess glucose metabolism, hepatic insulin sensitivity, metabolic flexibility, and clinical signs of metabolic syndrome development. Existing exposure data including methylmercury, PCB, and DDE, will now be complemented by analyses of perfluorinated compounds in cord blood and postnatal samples. To establish an epigenetic signature for these exposures we will conduct a genome-wide epigenetic mapping using DNA extracted from whole blood from cohort members. We will examine CpG islands and shores, CpG outside islands, non-CpG methylated sites identified in human cancer stem cells, miRNA promoter regions and disease-associated regions identified through GWAS. The total and site-specific DNA methylations will be linked to exposures to environmental chemicals at birth and postnatally and to clinical indicators of glucose metabolism and metabolic flexibility. Determinations of exposures to the pollutants associated with subclinical changes related to type 2 diabetes, whether these changes are mediated by DNA methylation, and whether they are affected by changes in body weight. These results will therefore contribute to our understanding of developmental programming effects of environmental chemicals, as indicated by DNA methylation, and their role in type 2 diabetes pathogenesis.