PMID- 27173514 OWN - NLM STAT- MEDLINE DCOM- 20180119 LR - 20190318 IS - 1873-6750 (Electronic) IS - 0160-4120 (Linking) VI - 92-93 DP - 2016 Jul-Aug TI - Association between exposures to brominated trihalomethanes, hepatic injury and type II diabetes mellitus. PG - 486-93 LID - S0160-4120(16)30142-8 [pii] LID - 10.1016/j.envint.2016.04.012 [doi] AB - Non-alcoholic fatty liver disease (NAFLD) is considered the most common liver disorder in the Western world, commonly diagnosed in the majority of obese patients with type 2 diabetes mellitus (T2DM). Metabolic disrupting chemicals with short half-lives, such as those of halogenated structure (trihalomethanes, THM) have been linked with hepatic insulin resistance phenomena in animal studies. However, human studies evaluating the role of THM exposure on liver pathogenesis and T2DM disease process are scarce. The objectives of this study were to: i) determine the association of urinary brominated THM (BrTHM) levels and T2DM disease status, and ii) investigate the association between urinary BrTHM levels and serum alanine aminotransferase (ALT) concentrations, often used as surrogate markers of NAFLD. A pilot case-control study was conducted in Nicosia, Cyprus (n=95). Cases were physician-diagnosed T2DM patients and controls were healthy individuals. Liver enzymes, leptin and TNF-alpha were measured in sera, while urinary THM levels were measured using tandem mass spectrometry. Diabetics had higher levels of serum leptin, body mass index and ALT than the controls. Among all study participants those with serum ALT levels above the median (17IU/L) had higher mean tribromomethane (TBM) concentrations compared to those with serum ALT below 17IU/L. A significant increase in the odds of having above the median serum ALT levels [OR 6.38, 95% CI: 1.11, 42.84 (p=0.044)] was observed for each unit increase in creatinine-unadjusted urinary TBM levels, along with BMI and past smoking, after adjusting for possible confounders, such as urinary creatinine, age, sex, and leptin; no other THM compound showed a significant association with serum ALT. Logistic regression models for T2DM using the urinary BrTHM as exposure variables did not reach the predetermined level of significance. The interplay between exposures to BrTHM and the initiation of key pathophysiological events relating to hepatic injury (ALT) and inflammation (leptin) was recognized via the use of selected biomarkers of effect. Our evidence that THM could act as hepatic toxins with a further initiation of diabetogenic effects call for additional studies to help us better understand the disease process of the two co-morbidities (NAFLD and T2DM). CI - Copyright (c) 2016 Elsevier Ltd. All rights reserved. FAU - Makris, Konstantinos C AU - Makris KC AD - Cyprus International Institute for Environmental and Public Health, Cyprus University of Technology, Limassol, Cyprus. Electronic address: konstantinos.makris@cut.ac.cy. FAU - Andrianou, Xanthi D AU - Andrianou XD AD - Cyprus International Institute for Environmental and Public Health, Cyprus University of Technology, Limassol, Cyprus. FAU - Charisiadis, Pantelis AU - Charisiadis P AD - Cyprus International Institute for Environmental and Public Health, Cyprus University of Technology, Limassol, Cyprus. FAU - Burch, James B AU - Burch JB AD - South Carolina Statewide Cancer Prevention & Control Program, University of South Carolina, Columbia, SC, USA; Department of Epidemiology and Biostatistics, Arnold School of Public Health, University of South Carolina, Columbia, SC, USA; Dorn Department of Veterans Affairs Medical Center, Columbia, SC, USA. FAU - Seth, Ratanesh K AU - Seth RK AD - Environmental Health & Disease Laboratory, Department of Environmental Health Sciences, Arnold School of Public Health, University of South Carolina, Columbia, SC, USA. FAU - Ioannou, Androniki AU - Ioannou A AD - Cyprus International Institute for Environmental and Public Health, Cyprus University of Technology, Limassol, Cyprus. FAU - Picolos, Michael AU - Picolos M AD - Endocrinology Clinic, Nicosia, Cyprus. FAU - Christophi, Costas A AU - Christophi CA AD - Cyprus International Institute for Environmental and Public Health, Cyprus University of Technology, Limassol, Cyprus. FAU - Chatterjee, Saurabh AU - Chatterjee S AD - Environmental Health & Disease Laboratory, Department of Environmental Health Sciences, Arnold School of Public Health, University of South Carolina, Columbia, SC, USA. Electronic address: schatt@mailbox.sc.edu. LA - eng GR - R00 ES019875/ES/NIEHS NIH HHS/United States PT - Journal Article DEP - 20160510 PL - Netherlands TA - Environ Int JT - Environment international JID - 7807270 RN - 0 (Biomarkers) RN - 0 (Leptin) RN - 0 (Trihalomethanes) RN - 0 (Water Pollutants, Chemical) RN - EC 2.6.1.2 (Alanine Transaminase) SB - IM MH - Adult MH - Aged MH - Alanine Transaminase/blood MH - Biomarkers/blood MH - Body Mass Index MH - Case-Control Studies MH - Diabetes Mellitus, Type 2/*epidemiology/urine MH - Environmental Monitoring MH - Female MH - Halogenation MH - Humans MH - Inflammation/blood MH - Leptin/blood MH - Logistic Models MH - Male MH - Middle Aged MH - Non-alcoholic Fatty Liver Disease/*epidemiology/urine MH - Trihalomethanes/*urine MH - Water Pollutants, Chemical/*urine OTO - NOTNLM OT - *Brominated trihalomethanes OT - *Diabetes OT - *Disinfection byproducts OT - *Fatty liver OT - *Inflammation OT - *Non-alcoholic OT - *Obesity EDAT- 2016/05/14 06:00 MHDA- 2018/01/20 06:00 CRDT- 2016/05/14 06:00 PHST- 2016/01/05 00:00 [received] PHST- 2016/04/07 00:00 [revised] PHST- 2016/04/08 00:00 [accepted] PHST- 2016/05/14 06:00 [entrez] PHST- 2016/05/14 06:00 [pubmed] PHST- 2018/01/20 06:00 [medline] AID - S0160-4120(16)30142-8 [pii] AID - 10.1016/j.envint.2016.04.012 [doi] PST - ppublish SO - Environ Int. 2016 Jul-Aug;92-93:486-93. doi: 10.1016/j.envint.2016.04.012. Epub 2016 May 10.