There is a striking interaction of genes and environment in the etiology of type 2 diabetes mellitus (T2DM). While endocrine disrupting chemicals (EDCs) like bisphenol-A ( ) have received special attention for their mechanistic role in metabolic disruption, there is a lack of clinically relevant data on levels in Asian Indians, a population which is more susceptible to type 2 diabetes mellitus (T2DM) and cardiovascular diseases. Therefore, we measured systemic levels of in patients with T2DM compared to individuals with normal glucose tolerance (na=a30 each). Serum levels were estimated using ELISA kit, and biochemical determinations were done by standard protocols. Peripheral blood mononuclear cells (PBMCs) were used to profile the gene expression alterations with special reference to inflammation, estrogen receptors, and cellular senescence in these subjects. Serum levels of were significantly higher in patients with T2DM compared to control individuals and positively correlated to poor glycemic control and insulin resistance. Patients with T2DM exhibited significantly elevated mRNA levels of senescence (GLB1, p16, p21, and p53) and inflammatory (IL6 and TNF-I+-) markers, shortened telomeres as well as elevated levels of estrogen-related receptor gamma (ERRI3), a recently identified receptor for . levels were positively correlated to senescence indicators, inflammatory markers and ERRI3 and negatively correlated to telomere length. Our study is the first data in the clinical diabetes setting to demonstrate an association of increased levels with cellular senescence, proinflammation, poor glycemic control, insulin resistance, and shortened telomeres in patients with T2DM.
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This project is supported by the Canadian Institutes of Health Research (award #111062), Alberta Innovates - Health Solutions, and by The Metabolomics Innovation Centre (TMIC), a nationally-funded research and core facility that supports a wide range of cutting-edge metabolomic studies. TMIC is funded by Genome Alberta, Genome British Columbia, and Genome Canada, a not-for-profit organization that is leading Canada's national genomics strategy with $900 million in funding from the federal government.