Associations of Serum Persistent Organic Pollutant Concentrations with Incident Diabetes in Midlife Women: The Study of Women's Health Across the Nation Multi-Pollutant Study

Abstract

BackgroundOrganochlorine pesticides (OCPs), polybrominated diphenyl ethers (PBDEs), and polychlorinated biphenyls (PCBs) are persistent organic pollutants (POPs) that can negatively impact metabolic health through pathways including endocrine disruption. Few studies have evaluated diabetes risk associated with PBDEs. Little is known about the joint effect of exposure to POP mixtures on diabetes risk.ObjectivesWe investigated the relationship between POPs, individually and as mixtures, and diabetes development over 18 years (1999-2016) in midlife women.MethodsWe measured lipid-standardized serum concentrations of 14 PCBs, 4 OCPs, and 1 PBDE in 1,040 midlife women aged 45-56 years from the Study of Women’s Health Across the Nation. We tested the association between POPs measured in 1999/2000 and incident diabetes assessed using Cox proportional hazards models. We evaluated diabetes risk associated with the overall POP mixture using Quantile-Based G-Computation (QBGC).ResultsFor most mixture components, single pollutant and mixtures analyses indicated null associations with diabetes risk, however results were inconsistent. After adjustment, hazard ratios (HRs) of developing diabetes (95% CI) associated with upper exposure tertiles (T2/T3) compared with the first tertile (T1), were 1.7 (1.0, 2.8) at T2 and 1.5 (0.84, 2.7) at T3 for hexachlorobenzene and 1.9 (1.1, 3.3) at T2 and 1.6 (0.88, 2.9) at T3 for PCB-123. After additional adjustment for waist circumference, PCB-138 was inversely associated with diabetes (T2 HR=0.77 [0.45, 1.33]; T3 HR=0.50 [0.26, 0.97]; p for trend=0.04). QBGC identified no association for the overall joint effect of the POP mixture on diabetes (HR=1.04 [0.53, 2.07]).ConclusionExposure to a mixture of PCBs, OCPs, and PBDEs was not associated with incident diabetes in midlife U.S. women, although some individual POPs demonstrated significant yet inconsistent associations with diabetes. Non-linear and non-monotonic dose-response dynamics deserve further exploration. More research is needed on the diabetogenic effects of PBDEs.

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Funding declaration: Funding The Study of Women’s Health Across the Nation (SWAN) has grant support from the National Institutes of Health (NIH), DHHS, through the National Institute on Aging (NIA), the National Institute of Nursing Research (NINR) and the NIH Office of Research on Women’s Health (ORWH) (Grants U01NR004061; U01AG012505, U01AG012535, U01AG012531, U01AG012539, U01AG012546, U01AG012553, U01AG012554, U01AG012495, and U19AG063720). The study was also supported by the SWAN Repository (U01AG017719). This publication was supported in part by the National Center for Research Resources and the National Center for Advancing Translational Sciences, National Institutes of Health, through UCSF-CTSI Grant Number UL1 RR024131. This study was also supported by grants from the National Institute of Environmental Health Sciences (NIEHS) R01-ES026578, R01-ES026964 and P30-ES017885, and by the Center for Disease Control and Prevention (CDC)/National Institute for Occupational Safety and Health (NIOSH) grant T42-OH008455. Amelia Grant-Alfieri was also supported by the Environmental Toxicology and Epidemiology (ETEP) training grant from NIEHS (T32 ES007062).

Conflict of Interests: The authors declare no competing interests.

Ethical Approval: . The institutional review board at each site approved the study protocol and all participants provided written, signed informed consent at each study visit.

Keywords: persistent organic pollutants, PCBs, Pesticides, PBDEs, Women, Diabetes