Plasma metabolites associated with exposure to perfluoroalkyl substances and risk of type 2 diabetes - A nested case-control study

Tessa Schillemans; Lin Shi; Carolina Donat-Vargas; Kati Hanhineva; Andreas Tornevi; Ingegerd Johansson; Jani Koponen; Hannu Kiviranta; Olov Rolandsson; Ingvar A Bergdahl; Rikard Landberg; Agneta Åkesson; Carl Brunius

doi:10.1016/j.envint.2020.106180

Plasma metabolites associated with exposure to perfluoroalkyl substances and risk of type 2 diabetes - A nested case-control study

Environ Int. 2021 Jan:146:106180. doi: 10.1016/j.envint.2020.106180. Epub 2020 Oct 25.

Authors

Affiliations

¹ Cardiovascular and Nutritional Epidemiology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden. Electronic address: [email protected].
² Department of Biology and Biological Engineering, Chalmers University of Technology, Gothenburg, Sweden; School of Food Engineering and Nutritional Science, Shaanxi Normal University, Xi'an, China.
³ Cardiovascular and Nutritional Epidemiology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden; Department of Preventive Medicine and Public Health, School of Medicine, Universidad Autónoma de Madrid, CEI UAM+CSIC, Madrid, Spain.
⁴ Department of Biology and Biological Engineering, Chalmers University of Technology, Gothenburg, Sweden; Institute of Public Health and Clinical Nutrition, University of Eastern Finland, Kuopio, Finland; Department of Biochemistry, University of Turku, Turku, Finland.
⁵ Department of Public Health and Clinical Medicine, Section of Sustainable Health, Umeå University, Umeå, Sweden.
⁶ Departments of Odontology, Umeå University, Umeå, Sweden.
⁷ Department for Health Security, Environmental Health Unit, Finnish Institute for Health and Welfare, Kuopio, Finland.
⁸ Department of Public Health and Clinical Medicine, Family Medicine, Umeå University, Umeå, Sweden.
⁹ Department of Biology and Biological Engineering, Chalmers University of Technology, Gothenburg, Sweden; Department of Public Health and Clinical Medicine, Section of Sustainable Health, Umeå University, Umeå, Sweden.
¹⁰ Cardiovascular and Nutritional Epidemiology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
¹¹ Department of Biology and Biological Engineering, Chalmers University of Technology, Gothenburg, Sweden.

PMID: 33113464
DOI: 10.1016/j.envint.2020.106180

Abstract

Perfluoroalkyl substances (PFAS) are widespread persistent environmental pollutants. There is evidence that PFAS induce metabolic perturbations in humans, but underlying mechanisms are still unknown. In this exploratory study, we investigated PFAS-related plasma metabolites for their associations with type 2 diabetes (T2D) to gain potential mechanistic insight in these perturbations. We used untargeted LC-MS metabolomics to find metabolites related to PFAS exposures in a case-control study on T2D (n = 187 matched pairs) nested within the Västerbotten Intervention Programme cohort. Following principal component analysis (PCA), six PFAS measured in plasma appeared in two groups: 1) perfluorononanoic acid, perfluorodecanoic acid and perfluoroundecanoic acid and 2) perfluorohexane sulfonic acid, perfluorooctane sulfonic acid and perfluorooctanoic acid. Using a random forest algorithm, we discovered metabolite features associated with individual PFAS and PFAS exposure groups which were subsequently investigated for associations with risk of T2D. PFAS levels correlated with 171 metabolite features (0.16 ≤ |r| ≤ 0.37, false discovery rate (FDR) adjusted p < 0.05). Out of these, 35 associated with T2D (p < 0.05), with 7 remaining after multiple testing adjustment (FDR < 0.05). PCA of the 35 PFAS- and T2D-related metabolite features revealed two patterns, dominated by glycerophospholipids and diacylglycerols, with opposite T2D associations. The glycerophospholipids correlated positively with PFAS and associated inversely with risk for T2D (Odds Ratio (OR) per 1 standard deviation (1-SD) increase in metabolite PCA pattern score = 0.2; 95% Confidence Interval (CI) = 0.1-0.4). The diacylglycerols also correlated positively with PFAS, but they associated with increased risk for T2D (OR per 1-SD = 1.9; 95% CI = 1.3-2.7). These results suggest that PFAS associate with two groups of lipid species with opposite relations to T2D risk.

Keywords: Metabolomics; Nested case-control study; Perfluoroalkyl substances; Type 2 Diabetes.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Alkanesulfonic Acids* / toxicity
Case-Control Studies
Diabetes Mellitus, Type 2* / etiology
Environmental Pollutants* / toxicity
Fluorocarbons* / toxicity
Humans
Plasma

Substances

Alkanesulfonic Acids
Environmental Pollutants
Fluorocarbons