Association of Perfluoroalkyl and Polyfluoroalkyl Substances With Adiposity

Abstract

Importance: Perfluoroalkyl and polyfluoroalkyl substances (PFASs) are ubiquitous synthetic chemicals that are suspected endocrine disruptors.

Objectives: To determine the extent to which PFASs are associated with increases in weight and body size and evaluate whether a lifestyle intervention modifies this association.

Design, setting, and participants: This prospective cohort study included 957 individuals who participated in the Diabetes Prevention Program trial, conducted from July 1996 to May 2001, and the Diabetes Prevention Program Outcomes Study, conducted from September 2002 to January 2014. Statistical analysis was conducted from September 1, 2017, to May 25, 2018.

Interventions and exposures: The initial lifestyle intervention consisted of training in diet, physical activity, and behavior modification, with the major goals of achieving 7% weight loss with subsequent maintenance and a minimum of 150 minutes per week of physical activity. Participants randomized to placebo received standard information about diet and exercise. A total of 6 plasma PFASs were quantified at baseline and 2 years after randomization, means were calculated from baseline and year 2 concentrations, and means were summed to assess total PFAS burden.

Main outcomes and measures: Weight, waist circumference, and hip girth were measured at baseline and at scheduled visits.

Results: Of the 957 participants, 625 (65.3%) were women and 731 participants (76.4%) were between 40 and 64 years of age; 481 participants were randomized to the lifestyle intervention and 476 participants were randomized to the placebo arm. The PFAS concentrations were not different by treatment arm and were similar to concentrations reported for the US population in 1999-2000. The association of PFAS and weight change differed by treatment. Each doubling in total PFAS concentration was associated with an increase of 1.80 kg (95% CI, 0.43-3.17 kg; P = .01) from baseline to 9 years after randomization for the placebo group but not the lifestyle intervention group (-0.59 kg; 95% CI, -1.80 to 0.62 kg; P = .34). Similarly, each doubling in PFAS was associated with a 1.03-cm increase in hip girth in the Diabetes Prevention Program trial for the placebo group (95% CI, 0.18-1.88 cm; P = .02) but not the lifestyle intervention group (-0.09 cm; 95% CI, -0.82 to 0.63 cm; P = .80). No associations were observed for changes in mean waist circumference.

Conclusions and relevance: Among adults at high risk for diabetes, higher plasma PFAS concentration was associated with increases in weight and hip girth over time, but a lifestyle intervention attenuated these associations. Diet and exercise may mitigate the obesogenic effects of environmental chemicals.

Trial registration: ClinicalTrials.gov Identifier: NCT00004992 and NCT00038727.

Conflict of interest statement

Conflict of Interest Disclosures: Dr Cardenas reported receiving grants from the National Institutes of Health (NIH) during the conduct of the study. Dr Hauser reported receiving grants from the NIH during the conduct of the study. Dr Gold reported receiving grants from the NIH during the conduct of the study. Dr Kleinman reported receiving grants from the NIH during the conduct of the study. Dr Fleisch reported receiving grants from the NIH during the conduct of the study. Dr Horton reported receiving personal fees from PTS Diagnostics, Takeda, and Theracos outside the submitted work. Dr Oken reported receiving grants from the NIH during the conduct of the study. No other disclosures were reported.

Figures

Figure 1.. Geometric Means for Select Perfluoroalkyl and Polyfluoroalkyl Substances (PFASs) Measured in the US National Health and Nutrition Examination Survey (NHANES) 1999-2014 and the Diabetes Prevention Program (DPP) at Baseline and Year 2

Trends in PFASs for the US population as well as the study sample. PFHxS indicates perfluorohexane sulfonic acid; PFNA, perfluorononanoic acid; PFOA, perfluorooctanoic acid; and PFOS, perfluorooctane sulfonic acid.

Figure 2.. Estimates and 95% CIs Among Adjusted Cross-sectional Associations of Outcomes per Doubling in Perfluoroalkyl and Polyfluoroalkyl Substance (PFAS) Concentrations Measured at Baseline

Cross-sectional associations of PFASs and adiposity. Et-PFOSA-AcOH indicates N-ethyl-perfluorooctane sulfonamido acetic acid; Me-PFOSA-AcOH, N-methyl-perfluorooctane sulfonamido acetic acid; L4-L5, lumbar vertebrae; PFHxS, perfluorohexane sulfonic acid; PFNA, perfluorononanoic acid; PFOA, perfluorooctanoic acid; and PFOS, perfluorooctane sulfonic acid.

Figure 3.. Adjusted Estimated Change in Weight and Body Size From Baseline at the 25th and 75th Percentiles of Total Mean Perfluoroalkyl and Polyfluoroalkyl Substances (PFASs)

A, Adjusted estimated change in weight from baseline at the 25th and 75th percentiles of total mean PFASs. B, Adjusted estimated change in waist circumference from baseline at the 25th and 75th percentiles of total mean PFASs. C, Adjusted estimated change in hip girth from baseline at the 25th and 75th percentiles of total mean PFASs. DPP indicates Diabetes Prevention Program.