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

• Published in: Metabolomics 2019-04, Vol.15 (4), p.60-16, Article 60
• Main Authors: Gängler, Stephanie, Waldenberger, Melanie, Artati, Anna, Adamski, Jerzy, van Bolhuis, Jurjen N., Sørgjerd, Elin Pettersen, van Vliet-Ostaptchouk, Jana, Makris, Konstantinos C.
• Format: Article
• Language: English
• Subjects: Adult; Biochemistry; Biomarkers; Biomarkers - blood; Biomarkers - urine; Biomedical and Life Sciences; Biomedicine; Case-Control Studies; Cell Biology; Chloroform; Chloroform - adverse effects; Cohort Studies; Developmental Biology; Diabetes; Diabetes mellitus; Diabetes mellitus (non-insulin dependent); Diabetes Mellitus, Type 2 - etiology; Diabetes Mellitus, Type 2 - metabolism; Disinfectants - adverse effects; Disinfection; Female; Halogenation; Humans; Life Sciences; Male; Mass spectroscopy; Metabolism; Metabolites; Metabolomics; Metabolomics - methods; Middle Aged; Molecular Medicine; Original Article; Prediction models; Prospective Studies; Risk Factors; Trihalomethanes; Trihalomethanes - adverse effects; Trihalomethanes - metabolism
• ISSN: 1573-3882; 1573-3890
• DOI: 10.1007/s11306-019-1519-0

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.