Poster Presentation Australian Diabetes Society and the Australian Diabetes Educators Association Annual Scientific Meeting 2017

Association of increased bisphenol-A (BPA) levels with poor glycemic control and accelerated ageing signatures in patients with Type 2 Diabetes. (#350)

Avinash Soundararajan 1 , Prabu Paramasivam 2 , Mohan Viswanathan 2 , Yann Gibert 1 , Balasubramanyam Muthuswamy 2
  1. Metabolic Research Unit/School of Medicine, Deakin University, Geelong, Victoria, Australia
  2. Cell and Molecular Biology, Madras Diabetes Research Foundation, Chennai, Tamil Nadu, India

Epidemiological studies indicate that the increased presence of endocrine disrupting chemicals (EDCs) in the environment may also play an important role in the incidence of metabolic diseases. Recently bisphenol-A (BPA), one of the most common EDCs received special attention in the development of insulin resistance and type 2 diabetes mellitus (T2DM). However, there is lack of data on this in Asian Indians, a population highly vulnerable to diabetes and its vascular complications. Therefore, we investigated the systemic levels of BPA in patients with T2DM compared to control subjects with normal glucose tolerance (n=30 each). In addition, peripheral blood mononuclear cells (PBMCs) were utilized to profile the gene expression alterations with special reference to inflammation and cellular senescence in these subjects. Serum levels of BPA was significantly (p<0.05) increased in patients T2DM compared to control subjects. BPA levels in patients with T2DM were also positively correlated to poor glycemic control and insulin resistance. Transcriptional analysis in PBMCs revealed that patients with T2DM exhibited significantly (p<0.05) elevated mRNA levels of senescence (β-gal, p16, p21 and p53) and inflammatory (IL6 and TNF-α) markers. The chronic burden of senescence and inflammation was also mirrored by significantly (p<0.05) shortened telomeres in patients with T2DM compared to control subjects. Most interestingly, PBMCs from patients with T2DM also exhibited significantly (p<0.05) elevated mRNA expression of ERRgamma – a newly identified receptor for BPA which has also recently been linked to elevated hepatic gluconeogenesis. For the first-time, our study has holistically demonstrated an association increased BPA levels with accelerated ageing characteristics (cellular senescence and proinflammation) implicating a role of ‘senescence associated secretory phenotype’ (SASP) alterations in patients with T2DM. Furthering research on this direction is expected to unravel novel drug targets and development of newer therapeutic measures for T2DM and associated metabolic disorders.