Persistent Organic Pollutants and Type 2 Diabetes Mellitus. Addressing causality with repeated measurements using novel study designs

Abstract

<p><i>Background:</i> Persistent Organic Pollutants (POPs) are chemicals that have negative impacts on the environment and biota and have been investigated as possible risk factors for Type 2 Diabetes Mellitus (T2DM). Other well-established risk factors for T2DM, for example, obesity, increased lipids, and age have been reported to influence human POP concentrations. Previous studies have reported positive associations between single POP measurement and prevalent and incident T2DM, although causality has not been established. Longitudinal studies with repeated pre-diagnostic POP measurements, which may help in addressing causality, are lacking. <p><i>Aims:</i> This thesis aimed to investigate if the different classes of POPs (perfluoroalkyl acids [PFAAs], polychlorinated biphenyls [PCBs], organochlorine pesticides [OCPs], and polybrominated diphenyl ethers [PBDEs]) are causal factors of T2DM using repeated POP measurements from the same individuals. We also assessed if T2DM status influences the body burden of POPs. <p><i>Methods:</i> We used questionnaire data and blood samples from two different population-based studies. The Norwegian Women and Cancer study was used to investigate PFAAs-T2DM associations and time trends in PFAAs (2001-2005/06) with two repeated measurements. The Tromsø study was used to study the associations between PCBs, OCPs, PBDEs, and T2DM, and time trends (1986-2016) in cases and controls using three to five repeated POP measurements per individual. <p><i>Results:</i> Among the PCBs and OCPs, only cis-heptachlor epoxide showed strong pre- and post-diagnostic associations. Further, PCBs and OCPs declined slower in cases compared to controls. PFAAs and PBDEs showed similar time trends in cases and controls, and these POPs were not associated with T2DM before or after diagnosis. <p><i>Conclusion:</i> The results from this thesis do not support POPs being causal factors of T2DM but suggest that T2DM-related physiological changes may cause retention of certain POPs already years before T2DM diagnosis leading to higher concentrations in prospective cases, and thus, positive associations with T2DM status.