title: DNA methylation and its role in the pathogenesis of diabetes.
abstract: Although the factors responsible for the recent increase in the prevalence of diabetes worldwide are not entirely known, the morbidity associated with this disease results in substantial health and economic burden on society. Epigenetic modifications, including DNA methylation have been identified as one mechanism by which the environment interacts with the genome and there is evidence that alterations in DNA methylation may contribute to the increased prevalence of both type 1 and type 2 diabetes. This review provides a summary of DNA methylation and its role in gene regulation, and includes descriptions of various techniques to measure site-specific and genome-wide DNA methylation changes. In addition, we review current literature highlighting the complex relationship between DNA methylation, gene expression, and the development of diabetes and related complications. In studies where both DNA methylation and gene expression changes were reported, DNA methylation status had a strong inverse correlation with gene expression, suggesting that this interaction may be a potential future therapeutic target. We highlight the emerging use of genome-wide DNA methylation profiles as a biomarker to predict patients at risk of developing diabetes or specific complications of diabetes. The development of a predictive model that incorporates both genetic sequencing and DNA methylation data may be an effective diagnostic approach for all types of diabetes and could lead to additional innovative therapies.
authors.affiliation: Center for Research on Reproduction and Women's Health, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.|Center of Excellence in Environmental Toxicology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.|Division of Neonatology, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania.
authors.forename: Amita
authors.initials: A
authors.lastname: Bansal
authors.affiliation: Center for Research on Reproduction and Women's Health, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.|Center of Excellence in Environmental Toxicology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.|Division of Endocrinology and Diabetes, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania.|Department of Pediatrics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.
authors.forename: Sara E
authors.identifier: 0000-0001-7824-2999
authors.initials: SE
authors.lastname: Pinney
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D003131:Combined Modality Therapy; D019175:DNA Methylation; D048909:Diabetes Complications / Q000453:epidemiology / Q000517:prevention & control; D003922:Diabetes Mellitus, Type 1 / Q000150:complications / Q000235:genetics / Q000378:metabolism* / Q000628:therapy; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000235:genetics / Q000378:metabolism* / Q000628:therapy; D044127:Epigenesis, Genetic; D018507:Gene Expression Regulation, Developmental; D019456:Health Transition; D006801:Humans; D007333:Insulin Resistance; D012307:Risk Factors
chemical_list: D015415:Biomarkers
keywords: DNA methylation; epigenetics; insulin secretion; insulin sensitivity; islets; type 2 diabetes