TY - JOUR
T1 - Per- and polyfluoroalkyl substance plasma concentrations and metabolomic markers of type 2 diabetes in the Diabetes Prevention Program trial
AU - Mitro, Susanna D.
AU - Liu, Jinxi
AU - Jaacks, Lindsay M.
AU - Fleisch, Abby F.
AU - Williams, Paige L.
AU - Knowler, William C.
AU - Laferrère, Blandine
AU - Perng, Wei
AU - Bray, George A.
AU - Wallia, Amisha
AU - Hivert, Marie France
AU - Oken, Emily
AU - James-Todd, Tamarra M.
AU - Temprosa, Marinella
N1 - Funding Information:
The authors thank Andres Cardenas, Diane Gold, Pi-I Debby Lin, Russ Hauser, Tom Webster, and the metabolomics working group in the Channing Division of Network Medicine at Brigham and Women's Hospital for constructive feedback to the analysis plan and thoughtful guidance on interpreting the results. The Research Group gratefully acknowledges the commitment and dedication of the participants of the DPP and DPPOS. Research reported in this publication was supported by the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) of the National Institutes of Health ( NIH ) under Award Number U01 DK048489 , by providing funding during DPP and DPPOS to the clinical centers and the Coordinating Center for the design and conduct of the study, and collection, management, analysis, and interpretation of the data. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. The Southwestern American Indian Centers were supported directly by the NIDDK , including its Intramural Research Program, and the Indian Health Service . The General Clinical Research Center Program , National Center for Research Resources , and the Department of Veterans Affairs supported data collection at many of the clinical centers. Funding was also provided by the National Institute of Child Health and Human Development , the National Institute on Aging , the National Eye Institute , the National Heart Lung and Blood Institute , the National Cancer Institute , the Office of Research on Women's Health , the National Institute on Minority Health and Health Disparities , the Centers for Disease Control and Prevention , and the American Diabetes Association . Merck KGaA provides medication for DPPOS. DPP/DPPOS have also received donated materials from Bristol-Myers Squibb, Parke-Davis, and LifeScan Inc. LifeScan Inc., Health O Meter, Hoechst Marion Roussel, Inc., Merck-Medco Managed Care, Inc., Merck and Co., Nike Sports Marketing, Slim Fast Foods Co., and Quaker Oats Co. donated materials, equipment, or medicines for concomitant conditions. McKesson BioServices Corp., Matthews Media Group, Inc., and the Henry M. Jackson Foundation provided support services under subcontract with the Coordinating Center. The sponsor of this study was represented on the Steering Committee and played a part in study design, how the study was done, and publication. All writing group authors had access to all data. The opinions expressed are those of the study group and do not necessarily reflect the views of the funding agencies. The Supplemental Material contains a complete list of Centers, investigators, and staff.
Funding Information:
The authors thank Andres Cardenas, Diane Gold, Pi-I Debby Lin, Russ Hauser, Tom Webster, and the metabolomics working group in the Channing Division of Network Medicine at Brigham and Women's Hospital for constructive feedback to the analysis plan and thoughtful guidance on interpreting the results. The Research Group gratefully acknowledges the commitment and dedication of the participants of the DPP and DPPOS. Research reported in this publication was supported by the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) of the National Institutes of Health (NIH) under Award Number U01 DK048489, by providing funding during DPP and DPPOS to the clinical centers and the Coordinating Center for the design and conduct of the study, and collection, management, analysis, and interpretation of the data. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. The Southwestern American Indian Centers were supported directly by the NIDDK, including its Intramural Research Program, and the Indian Health Service. The General Clinical Research Center Program, National Center for Research Resources, and the Department of Veterans Affairs supported data collection at many of the clinical centers. Funding was also provided by the National Institute of Child Health and Human Development, the National Institute on Aging, the National Eye Institute, the National Heart Lung and Blood Institute, the National Cancer Institute, the Office of Research on Women's Health, the National Institute on Minority Health and Health Disparities, the Centers for Disease Control and Prevention, and the American Diabetes Association. Merck KGaA provides medication for DPPOS. DPP/DPPOS have also received donated materials from Bristol-Myers Squibb, Parke-Davis, and LifeScan Inc. LifeScan Inc. Health O Meter, Hoechst Marion Roussel, Inc. Merck-Medco Managed Care, Inc. Merck and Co. Nike Sports Marketing, Slim Fast Foods Co. and Quaker Oats Co. donated materials, equipment, or medicines for concomitant conditions. McKesson BioServices Corp. Matthews Media Group, Inc. and the Henry M. Jackson Foundation provided support services under subcontract with the Coordinating Center. The sponsor of this study was represented on the Steering Committee and played a part in study design, how the study was done, and publication. All writing group authors had access to all data. The opinions expressed are those of the study group and do not necessarily reflect the views of the funding agencies. The Supplemental Material contains a complete list of Centers, investigators, and staff.This work was supported by the National Institutes of Health (T32-ES007069, K23ES024803, R01ES030101, R01ES024765).
Funding Information:
This work was supported by the National Institutes of Health ( T32-ES007069 , K23ES024803 , R01ES030101 , R01ES024765 ).
Publisher Copyright:
© 2020 Elsevier GmbH
PY - 2021/3
Y1 - 2021/3
N2 - Background: Per- and polyfluoroalkyl substances (PFAS) are widely used chemicals, some of which have been linked to type 2 diabetes. We tested whether PFAS concentrations were cross-sectionally associated with metabolites previously shown to predict incident type 2 diabetes using the Diabetes Prevention Program (DPP), a trial of individuals at high risk of type 2 diabetes. Methods: We evaluated 691 participants enrolled in the DPP with baseline measures of 10 PFAS (including total perfluorooctanesulfonic acid (PFOS), total perfluorooctanoic acid (PFOA), and Sb-PFOA [branched isomers of PFOA]) and 77 metabolites. We used log2-transformed PFAS concentrations as exposures and standardized metabolite concentrations as outcomes in linear regression models adjusted for age, sex, race/ethnicity, use of anti-hyperlipidemic or triglyceride-lowering medication, income, years of education, marital status, smoking, and family history of diabetes, with Benjamini-Hochberg linear step-up false discovery rate correction. Results: Sb-PFOA was associated with the largest number of tested metabolites (29 of 77). Each doubling in Sb-PFOA was associated with higher leucine (β = 0.07 [95%CI: 0.02, 0.11] SD) and lower glycine (−0.08 [95%CI: 0.03, −0.13] SD). Each doubling of either total PFOA or n-PFOA was associated with −0.13 [95%CI: 0.04, −0.22] SD lower glycine. PFOA and Sb-PFOA were positively associated with multiple triacylglycerols and diacylglycerols, and total PFOS, total PFOA, and Sb-PFOA were positively associated with phosphatidylethanolamines. Conclusions: PFAS concentrations are associated with metabolites linked to type 2 diabetes (particularly amino acid, glycerolipid and glycerophospholipid pathways). Further prospective research is needed to test whether these metabolites mediate associations of PFAS and type 2 diabetes.
AB - Background: Per- and polyfluoroalkyl substances (PFAS) are widely used chemicals, some of which have been linked to type 2 diabetes. We tested whether PFAS concentrations were cross-sectionally associated with metabolites previously shown to predict incident type 2 diabetes using the Diabetes Prevention Program (DPP), a trial of individuals at high risk of type 2 diabetes. Methods: We evaluated 691 participants enrolled in the DPP with baseline measures of 10 PFAS (including total perfluorooctanesulfonic acid (PFOS), total perfluorooctanoic acid (PFOA), and Sb-PFOA [branched isomers of PFOA]) and 77 metabolites. We used log2-transformed PFAS concentrations as exposures and standardized metabolite concentrations as outcomes in linear regression models adjusted for age, sex, race/ethnicity, use of anti-hyperlipidemic or triglyceride-lowering medication, income, years of education, marital status, smoking, and family history of diabetes, with Benjamini-Hochberg linear step-up false discovery rate correction. Results: Sb-PFOA was associated with the largest number of tested metabolites (29 of 77). Each doubling in Sb-PFOA was associated with higher leucine (β = 0.07 [95%CI: 0.02, 0.11] SD) and lower glycine (−0.08 [95%CI: 0.03, −0.13] SD). Each doubling of either total PFOA or n-PFOA was associated with −0.13 [95%CI: 0.04, −0.22] SD lower glycine. PFOA and Sb-PFOA were positively associated with multiple triacylglycerols and diacylglycerols, and total PFOS, total PFOA, and Sb-PFOA were positively associated with phosphatidylethanolamines. Conclusions: PFAS concentrations are associated with metabolites linked to type 2 diabetes (particularly amino acid, glycerolipid and glycerophospholipid pathways). Further prospective research is needed to test whether these metabolites mediate associations of PFAS and type 2 diabetes.
KW - Metabolomics
KW - PFAS
KW - Type 2 diabetes
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U2 - 10.1016/j.ijheh.2020.113680
DO - 10.1016/j.ijheh.2020.113680
M3 - Article
C2 - 33348273
AN - SCOPUS:85099500020
SN - 1438-4639
VL - 232
JO - International Journal of Hygiene and Environmental Health
JF - International Journal of Hygiene and Environmental Health
M1 - 113680
ER -
