Persistent Organic Pollutants and Metabolism in Midlife Women

Details

• Personal Author:
  Grant-Alfieri A
• Description:
  Many environmental chemicals are known or suspected risk factors for metabolic disease, including persistent organic pollutants (POPs) such as polychlorinated biphenyls (PCBs), polybrominated diphenyl ethers (PBDEs), and organochlorine pesticides (OCPs). These chemicals persist in the environment following agricultural, industrial, and commercial use in electronics, plastics, pesticides and pesticide extenders, fabrics, and furniture. PCBs and many OCPs were banned by the U.S. and other high-income countries in the 1970s and 1980s. In 2013, the U.S. banned many classes of PBDEs. Despite these phase-outs, humans are still exposed to POPs primarily via diet and, in the case of PCBs and PBDEs, indoor air and dust. Due to their lipophilicity, POPs are sequestered in adipose tissue, where they may impair adipocyte functioning. Disruption of adipokine hormones has been linked to cardiometabolic diseases. Changes in adiposity may redistribute POPs between serum and adipose tissue. The menopausal transition entails rapidly changing adiposity. This dissertation explored potential impacts of POPs on metabolism. The following aims were assessed in a longitudinal, multi-ethnic, multi-site cohort of U.S. midlife women, the Study of Women's Health Across the Nation. The three aims explored different facets of visceral adipose tissue, as it relates to internal exposure to POPs and metabolic health. Aim 1 Changes in adiposity may affect the sequestration and circulation of POPs. Few studies have repeated measures of POPs. We evaluated the relationship between changes in central adiposity and changes in circulating concentrations of PCBs and OCPs in 75 women over a twelve-year period (1999-2011). After multivariable adjustment, a one-inch increase in the difference in waist circumference between visits was associated with a 4.9% decrease in the difference in serum concentration of PCB 194 (95% CI: -8.0%, -1.6%). No associations were observed for other PCBs or OCPs. PCB 194, a highly lipophilic congener, may be sequestered in adipose tissue following adiposity gain. The study's main strength was measuring POPs at multiple timepoints. The study was limited by its small sample. Future research should investigate intra-person variation in serum POP concentrations and predictors of temporal trends. Aim 2 Little is known about the joint effect of exposure to mixtures of POPs on diabetes risk. Few studies have evaluated diabetes risk associated with PBDEs. We explored the association between serum concentrations of POPs, individually and as mixtures, and diabetes development over 18 years (1999-2016) in 1,400 women. Using single pollutant models, most POPs were not identified as being significantly associated with diabetes risk. After multivariable adjustment, the hazard ratio (HR) and 95% CI for diabetes associated with tertiles of exposure (T2 or T3), relative to the first tertile, was 1.7 at T2 (1.0, 2.8) and 1.5 at T3 (0.84, 2.7) for hexachlorobenzene and 1.9 at T2 (1.1, 3.3) and 1.6 at T3 (0.88, 2.9) for PCB 123. We observed no association between diabetes risk and moderate and high levels of exposure to p,p'-DDE, p,p'-DDT, and p,p'-DDD, relative to non-detection. Using Quantile Based G-Computation to account for co-pollutant confounding between POP mixture components, we observed no significant overall joint effect of the mixture on incident diabetes (HR = 1.04 [0.53, 2.07]). This is the first prospective diabetes study to use a mixtures approach. Furthermore, this is one of few studies that analyzed PBDEs in addition to PCBs and OCPs. More research is needed on the diabetogenic effects of PBDEs, ideally in a more highly exposed population. Aim 3 Little is known about the relationship between POPs, especially as mixtures, and adipokines. We investigated the relationship between serum concentrations of POPs measured in 1999/2000, individually and as mixtures, and serum levels of leptin and high molecular weight (HMW) adiponectin, a biologically active form of adiponectin, measured in 2002/2003 among 1,400 women. After multivariable adjustment, no significant associations were observed for the overall joint effect of the POP mixture on adipokines using Bayesian Kernel Machine Regression (BKMR) models. Based on single pollutant analyses, a one-interquartile range (IQR) higher PCB 194 concentration was associated with 9.0% lower (95% CI: -13.2%, -4.7%) leptin and 4.1% higher (95% CI: 0.35%, 7.9%) HMW adiponectin. A one-IQR higher PCB 180 concentration was associated with 5.2% lower (95% CI: -9.6%, -0.6%) leptin. This is the first study of POPs and adipokines in adults not restricted to patients with obesity. Another study strength was our attempt to improve the validity of exposure measurement between POP and adipokine collection timepoints; limiting our interpretation to women with stable adiposity, we controlled for a loss or gain of adipose tissue that could alter serum concentrations of POPs and adipokines. This study highlights the potential complexity of mechanisms underlying POPs and adipokines. Overall, this dissertation does not provide consistent evidence of an association between POP mixtures and incident diabetes or adipokines in U.S. midlife women. Discordant results between single pollutant and mixtures models may have been due to co-pollutant confounding, individual POPs affecting risk in different directions, and/or compound-specific mechanistic activity. Aims 2 and 3 are notable for their analysis of mixtures of PCBs, OCPs, and PBDEs using numerous modeling approaches. In all aims, the role of serum lipids and visceral adiposity were carefully considered. Another strength was the representation of women from multiple urban areas across the U.S. and a focus on Chinese and Japanese women who have been historically underrepresented in U.S. studies. The dissertation leverages SWAN's original design to characterize changes throughout the menopausal transition including changes in adiposity. Moving forward, research is needed on the effects of POPs, especially PBDEs, on the metabolic functioning of adipose tissue. Further research is also warranted on intra-person variation in serum POP concentrations and factors affecting trends in serum concentrations. [Description provided by NIOSH]
• Subjects:
  Blood Body Weight Energy Metabolism Environmental Exposure Hematologic Diseases Insecticides Occupational Health Polychlorinated Biphenyls Safety Women
• Keywords:
  Adipose Tissue Blood Sugar Disorders Body Weight Environmental Exposure Metabolism PCBs Pesticides Polybrominated Diphenyl Ethers Polychlorinated Biphenyls
• Publisher:
  University of Michigan
• Document Type:
  Text
• Funding:
  Grant
• Genre:
  Dissertation
• Place as Subject:
  Michigan ; OSHA Region 5
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Pages in Document:
  1-217
• NIOSHTIC Number:
  nn:20068714
• Citation:
  Ann Arbor, MI: University of Michigan, 2023 Jun; :1-217
• Federal Fiscal Year:
  2023
• Performing Organization:
  University of Michigan, Ann Arbor
• Peer Reviewed:
  False
• Start Date:
  20050701
• Source Full Name:
  Persistent organic pollutants and metabolism in midlife women
• End Date:
  20280630
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:dc775ad1b6f16a3ca3d6ca39aa0519a2a3a21cf24e70a26ba15145afa97197534051fb09bcae31829d6fe3661f850d90515c454632509db5416f98baf8d916b9
• Download URL:
  https://stacks.cdc.gov/view/cdc/207300/cdc_207300_DS1.pdf
• File Type:
  [PDF - 18.66 MB ]