The Environment-Wide Approach for the Assessment of the Effect of Environmental Stressors on Overweight, Obesity and Diabetes: A Study on Singletons for the Heals Project

摘要

One of the main aims of the HEALS project is to unravel, through an exposomic approach, the development of metabolic diseases. The objective of the present study was to investigate the relationship between body burden from endocrine disrupting chemicals (EDCs) exposure (Holtcamp, 2012; La Merrill and Birnbaum, 2011) and the onset of overweight, obesity and diabetes, in view to promote preventive actions. Data was obtained from several pre-existing European cohorts (REPRO-PL, Pll, PI2, IMCA, SEASD, CCM, PHIME-CRO, PHIME-SI, G21, EPITeen, EDEN, CHISQ200 and MAAS). They were harmonised and cleaned to obtain a final dataset of 28,608 individuals. To replace missing values, a multiple imputation methodology was used. The EWAS analysis employed a survey-weighted logistic regression method with a Bonferroni correction to adjust the probability values and counteract the problem of multiple comparisons. As dependent variables, the health outcomes considered were overweight (BMI>=25), obesity (BMI>=30) and type-2 diabetes mellitus. As independent variables, 70 environmental assays and other demographic factors, at different periods of life were included. Obesity was found to be positively and significantly associated with PM10 (OR=1.174, p-value=0.005), N02 (1.276, 0.030), PCB118 (2.687, 0.026)), zinc (1.098, 0.021) and several class of phthalates like MEHP (1.095, 0.026). A negative association was observed for some stressors like brominated diphenyl ether BDE153 (0.980, 0.001) and cadmium (0.868, 0.001). Comparable results were obtained for overweight and diabetes. Our EWAS analyses confirm potential association between multiple environmental factors and overweight, obesity and diabetes. Whether mechanisms underlying metabolic changes depend on adipocyte proliferation and differentiation, glucose homeostasis, insulin release or behaviour (traffic pollution may also lead to less physical activities and sedentary lifestyle) needs to be further investigated.