Serum biomarkers from cell-based assays for AhRL and MIS strongly predicted the future development of diabetes in a large community-based prospective study in Korea

• Published in: Scientific reports Vol. 10; no. 1; p. 6339
• Main Authors: Lee, Hong Kyu, Park, Wook Ha, Kang, Young Cheol, Kang, Sora, Im, Suyeol, Park, Sol, Kim, Jin Taek, Lee, Minhyeok, Seok, Junhee, Oh, Man-Suk, Choi, Hoon Sung, Pak, Youngmi Kim
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 14.04.2020; Nature Publishing Group
• Subjects: 692/163/2743; 692/499; 692/53; 692/53/2423; Aged; Air Pollutants - toxicity; ATP; Basic Helix-Loop-Helix Transcription Factors - blood; Basic Helix-Loop-Helix Transcription Factors - genetics; Biomarkers - blood; Chemical pollution; Contamination; Diabetes; Diabetes mellitus; Diabetes Mellitus - blood; Diabetes Mellitus - chemically induced; Diabetes Mellitus - pathology; Environmental Biomarkers - genetics; Epidemiology; Female; Gender; Genomes; Glucose Intolerance - blood; Glucose Intolerance - genetics; Glucose tolerance; Glucose Tolerance Test; Health risk assessment; Health risks; Humanities and Social Sciences; Humans; Insulin; Insulin Resistance - genetics; Ligands; Male; Middle Aged; Mitochondria; Mitochondria - drug effects; multidisciplinary; Reactive oxygen species; Reactive Oxygen Species - metabolism; Receptors, Aryl Hydrocarbon - blood; Receptors, Aryl Hydrocarbon - genetics; Republic of Korea; Risk assessment; Science; Science (multidisciplinary); Serum levels; Republic of Korea
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-020-62550-6

Exposure to environment-polluting chemicals (EPC) is associated with the development of diabetes. Many EPCs exert toxic effects via aryl hydrocarbon receptor (AhR) and/or mitochondrial inhibition. Here we investigated if the levels of human exposure to a mixture of EPC and/or mitochondrial inhibitors could predict the development of diabetes in a prospective study, the Korean Genome and Epidemiological Study (KoGES). We analysed AhR ligands (AhRL) and mitochondria-inhibiting substances (MIS) in serum samples (n = 1,537), collected during the 2008 Ansung KoGES survey with a 4-year-follow-up. Serum AhRL, determined by the AhR-dependent luciferase reporter assay, represents the contamination level of AhR ligand mixture in serum. Serum levels of MIS, analysed indirectly by MIS-ATP or MIS-ROS, are the serum MIS-induced mitochondria inhibiting effects on ATP content or reactive oxygen species (ROS) production in the cultured cells. Among 919 normal subjects at baseline, 7.1% developed impaired glucose tolerance (IGT) and 1.6% diabetes after 4 years. At the baseline, diabetic and IGT sera displayed higher AhRL and MIS than normal sera, which correlated with indices of insulin resistance. When the subjects were classified according to ROC cut-off values, fully adjusted relative risks of diabetes development within 4 years were 7.60 (95% CI, 4.23–13.64), 4.27 (95% CI, 2.38–7.64), and 21.11 (95% CI, 8.46–52.67) for AhRL ≥ 2.70 pM, MIS-ATP ≤ 88.1%, and both, respectively. Gender analysis revealed that male subjects with AhRL ≥ 2.70 pM or MIS-ATP ≤ 88.1% showed higher risk than female subjects. High serum levels of AhRL and/or MIS strongly predict the future development of diabetes, suggesting that the accumulation of AhR ligands and/or mitochondrial inhibitors in body may play an important role in the pathogenesis of diabetes.