Exposure to disinfection byproducts and risk of type 2 diabetes: a nested case-control study in the HUNT and Lifelines cohorts

Stephanie Gängler; Melanie Waldenberger; Anna Artati; Jerzy Adamski; Jurjen N van Bolhuis; Elin Pettersen Sørgjerd; Jana van Vliet-Ostaptchouk; Konstantinos C Makris

doi:10.1007/s11306-019-1519-0

Exposure to disinfection byproducts and risk of type 2 diabetes: a nested case-control study in the HUNT and Lifelines cohorts

Metabolomics. 2019 Apr 8;15(4):60. doi: 10.1007/s11306-019-1519-0.

Authors

Affiliations

¹ Water and Health Laboratory, Cyprus International Institute for Environmental and Public Health, Cyprus University of Technology, Irenes 95, 3041, Limassol, Cyprus.
² Research Unit of Molecular Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health, 85764, Neuherberg, Bavaria, Germany.
³ Institute of Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health, 85764, Neuherberg, Bavaria, Germany.
⁴ Research Unit Molecular Endocrinology and Metabolism, Genome Analysis Center, Helmholtz Zentrum München, German Research Center for Environmental Health, 85764, Neuherberg, Germany.
⁵ German Center for Diabetes Research (DZD e.V.), 85764, Neuherberg, Germany.
⁶ Chair of Experimental Genetics, Technical University of Munich, 85350, Freising, Germany.
⁷ Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, 117596, Singapore, Singapore.
⁸ Lifelines Research Office, The Lifelines Cohort, Bloemsingel 1, 9713 BZ, Groningen, The Netherlands.
⁹ HUNT Research Center, Department of Public Health and Nursing, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology, NTNU, Forskningsvegen 2, 7600, Levanger, Norway.
¹⁰ Department of Endocrinology, University Medical Center Groningen, University of Groningen, 9700, Groningen, The Netherlands.
¹¹ Department of Epidemiology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
¹² Water and Health Laboratory, Cyprus International Institute for Environmental and Public Health, Cyprus University of Technology, Irenes 95, 3041, Limassol, Cyprus. konstantinos.makris@cut.ac.cy.

PMID: 30963292
DOI: 10.1007/s11306-019-1519-0

Abstract

Introduction: Environmental chemicals acting as metabolic disruptors have been implicated with diabetogenesis, but evidence is weak among short-lived chemicals, such as disinfection byproducts (trihalomethanes, THM composed of chloroform, TCM and brominated trihalomethanes, BrTHM).

Objectives: We assessed whether THM were associated with type 2 diabetes (T2D) and we explored alterations in metabolic profiles due to THM exposures or T2D status.

Methods: A prospective 1:1 matched case-control study (n = 430) and a cross-sectional 1:1 matched case-control study (n = 362) nested within the HUNT cohort (Norway) and the Lifelines cohort (Netherlands), respectively, were set up. Urinary biomarkers of THM exposure and mass spectrometry-based serum metabolomics were measured. Associations between THM, clinical markers, metabolites and disease status were evaluated using logistic regressions with Least Absolute Shrinkage and Selection Operator procedure.

Results: Low median THM exposures (ng/g, IQR) were measured in both cohorts (cases and controls of HUNT and Lifelines, respectively, 193 (76, 470), 208 (77, 502) and 292 (162, 595), 342 (180, 602). Neither BrTHM (OR = 0.87; 95% CI: 0.67, 1.11 | OR = 1.09; 95% CI: 0.73, 1.61), nor TCM (OR = 1.03; 95% CI: 0.88, 1.2 | OR = 1.03; 95% CI: 0.79, 1.35) were associated with incident or prevalent T2D, respectively. Metabolomics showed 48 metabolites associated with incident T2D after adjusting for sex, age and BMI, whereas a total of 244 metabolites were associated with prevalent T2D. A total of 34 metabolites were associated with the progression of T2D. In data driven logistic regression, novel biomarkers, such as cinnamoylglycine or 1-methylurate, being protective of T2D were identified. The incident T2D risk prediction model (HUNT) predicted well incident Lifelines cases (AUC = 0.845; 95% CI: 0.72, 0.97).

Conclusion: Such exposome-based approaches in cohort-nested studies are warranted to better understand the environmental origins of diabetogenesis.

Keywords: Brominated disinfection byproducts; Disinfection byproducts; HUNT; LASSO; Lifelines; Metabolomics; Trihalomethanes; Type 2 diabetes.

Publication types

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

MeSH terms

Adult
Biomarkers / blood
Biomarkers / urine
Case-Control Studies
Chloroform / adverse effects
Cohort Studies
Diabetes Mellitus, Type 2 / etiology
Diabetes Mellitus, Type 2 / metabolism
Disinfectants / adverse effects*
Female
Halogenation
Humans
Male
Metabolomics / methods
Middle Aged
Prospective Studies
Risk Factors
Trihalomethanes / adverse effects*
Trihalomethanes / metabolism*

Substances

Biomarkers
Disinfectants
Trihalomethanes
Chloroform