Andres Cardenas1,2, Marie-France Hivert2,3, Diane R Gold4,5, Russ Hauser4, Ken P Kleinman6, Pi-I D Lin2, Abby F Fleisch7,8, Antonia M Calafat9, Xiaoyun Ye9, Thomas F Webster10, Edward S Horton11, Emily Oken2. 1. Division of Environmental Health Sciences, School of Public Health, University of California, Berkeley, Berkeley, CA andres.cardenas@berkeley.edu. 2. Division of Chronic Disease Research Across the Lifecourse, Department of Population Medicine, Harvard Medical School and Harvard Pilgrim Health Care Institute, Boston, MA. 3. Diabetes Unit, Massachusetts General Hospital, Boston, MA. 4. Department of Environmental Health, Harvard T.H. Chan School of Public Health, Boston, MA. 5. Channing Division of Network Medicine, Brigham and Women's Hospital, Boston, MA. 6. Department of Biostatistics and Epidemiology, University of Massachusetts-Amherst School of Public Health and Health Sciences, Amherst, MA. 7. Division of Pediatric Endocrinology and Diabetes, Maine Medical Center, Portland, ME. 8. Center for Outcomes Research and Evaluation, Maine Medical Center Research Institute, Portland, ME. 9. Division of Laboratory Sciences, National Center for Environmental Health, Centers for Disease Control and Prevention, Atlanta, GA. 10. Department of Environmental Health, Boston University School of Public Health, Boston, MA. 11. Joslin Diabetes Center, Harvard Medical School, Boston, MA.
Abstract
OBJECTIVE:Perfluoroalkyl and polyfluoroalkyl substances (PFASs) are suspected endocrine disruptors widely detected across populations. We examine the extent to which PFASs are associated with diabetes incidence and microvascular disease. Secondarily, we tested whether a lifestyle intervention modifies associations and decreases concentrations. RESEARCH DESIGN AND METHODS: We analyzed data from a prospective cohort of 957 participants from the Diabetes Prevention Program (DPP) trial and Diabetes Prevention Program Outcomes Study (DPPOS). At baseline, participants were randomized to an intensive lifestyle intervention of diet, physical activity, and behavior modification or a placebo medication. We quantified plasma concentrations of six PFASs at baseline and 2 years after randomization. Participants were monitored for ∼15 years, repeatedly tested for diabetes, and evaluated for microvascular disease at the end of the follow-up. RESULTS: A doubling in baseline branched perfluorooctanoic acid concentration was associated with a 14% increase in diabetes risk for the placebo (hazard ratio [HR] 1.14, 95% CI 1.04, 1.25) but not in the lifestyle intervention group (HR 1.01, 95% CI 0.92, 1.11, P interaction = 0.11). Mean change in plasma baselinebranched perfluorooctanoic acid concentration was greater for the placebo (0.96 ng/mL; 95% CI 0.71, 1.22) compared with the lifestyle intervention group (0.31 ng/mL; 95% CI 0.14, 0.48) 2 years after randomization. Each doubling in N-ethyl-perfluorooctane sulfonamido acetic acid was associated with 17% greater odds of prevalent microvascular disease (OR 1.17, 95% CI 1.05, 1.31), and a similar association was observed for perfluorodimethylhexane sulfonic acid (OR 1.18, 95% CI 1.04, 1.35), regardless of treatment. CONCLUSIONS: Some plasma PFASs were associated with diabetes and microvascular disease. Our results suggest that exercise and diet may attenuate the diabetogenic association of PFASs.
RCT Entities:
OBJECTIVE:Perfluoroalkyl and polyfluoroalkyl substances (PFASs) are suspected endocrine disruptors widely detected across populations. We examine the extent to which PFASs are associated with diabetes incidence and microvascular disease. Secondarily, we tested whether a lifestyle intervention modifies associations and decreases concentrations. RESEARCH DESIGN AND METHODS: We analyzed data from a prospective cohort of 957 participants from the Diabetes Prevention Program (DPP) trial and Diabetes Prevention Program Outcomes Study (DPPOS). At baseline, participants were randomized to an intensive lifestyle intervention of diet, physical activity, and behavior modification or a placebo medication. We quantified plasma concentrations of six PFASs at baseline and 2 years after randomization. Participants were monitored for ∼15 years, repeatedly tested for diabetes, and evaluated for microvascular disease at the end of the follow-up. RESULTS: A doubling in baseline branched perfluorooctanoic acid concentration was associated with a 14% increase in diabetes risk for the placebo (hazard ratio [HR] 1.14, 95% CI 1.04, 1.25) but not in the lifestyle intervention group (HR 1.01, 95% CI 0.92, 1.11, P interaction = 0.11). Mean change in plasma baseline branched perfluorooctanoic acid concentration was greater for the placebo (0.96 ng/mL; 95% CI 0.71, 1.22) compared with the lifestyle intervention group (0.31 ng/mL; 95% CI 0.14, 0.48) 2 years after randomization. Each doubling in N-ethyl-perfluorooctane sulfonamido acetic acid was associated with 17% greater odds of prevalent microvascular disease (OR 1.17, 95% CI 1.05, 1.31), and a similar association was observed for perfluorodimethylhexane sulfonic acid (OR 1.18, 95% CI 1.04, 1.35), regardless of treatment. CONCLUSIONS: Some plasma PFASs were associated with diabetes and microvascular disease. Our results suggest that exercise and diet may attenuate the diabetogenic association of PFASs.
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