The prevalence of metabolic syndrome, obesity and type 2 diabetes has dramatically increased worldwide during the last few decades and exceeds World Health Organisations predictions. It is not possible anymore to explain this real pandemic only by genetic predisposition and/or by classical lifestyle changes such as sedentary lifestyle or energy-dense diet. There is increasing experimental and epidemiological evidence suggesting that exposure to environmental factors such as noxy foods, dysbiosis or endocrine disrupting chemicals (EDCs) may also contribute to the prevalence of DT2. EDCs are natural or synthetic chemical compounds, present in the everyday domestic environment, interfering with hormonal regulation systems critical for energy homeostasis. Many are present in the food chain and after absorption are sequestred in adipose tissue. They may represent after low-doses exposure during sensitive windows or via chronic exposure to cumulative doses, one aspect of the genetic/environment interface, involved in the pathophysiology of DT2. In humans, some epidemiologic reports suggested a strong link between exposure to some persistent EDCs (pesticides, polychorinated biphenyls, bisphenol A, phthalates, dioxins, polycyclic aromatic hydrocarbons) and DT2, especially after acute and accidental releases of EDCs (Seveso plant explosion, Vietnam war veterans). Other cross-sectional studies around the world reported suggestive to strong association between diabetes and obesity and EDCs exposure, especially for persistent organic pollutants, which should be considered as insulin-resistance risk factors. In rodents, exposure to bisphenol A is responsible for modifications of insulin synthesis and secretion in pancreatic beta cells but also for modifications of insulin signaling in liver, skeletal muscle and adipose tissue, which both lead to insulin-resistanc. In vivo and in vitro experimental studies have shown that EDCs may act through nuclear receptors (ERs, AhR, PPARγ, ERRγ) involved in metabolic control and are able to induce in specific windows of exposure (fetal, perinatal, pre-pubertal periods) epigenetic changes (DNA methylation, histone modifications, miRNA dysregulation) programming later obesity, insulin resistance, and/or β cell failure. It is still necessary to better understand the involved molecular mechanisms, to develop additional human prospective, longitudinal case/control epidemiological studies, and to identify early biomarkers of exposure, in order to improve assessment of chronic exposure to mixture of EEDs in order to determine the real implication of EEDs in DT2 highly susceptible patients.
20 - 23 May 2017
European Society of Endocrinology