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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
- Title
- 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
- Authors
- Lee H.K.; Park W.H.; Kang Y.C.; Kang S.; Im S.; Park S.; Kim J.T.; Lee M.; Seok J.; Oh M.-S.; Choi H.S.; Pak Y.K.
- Ewha Authors
- 오만숙
- SCOPUS Author ID
- 오만숙
- Issue Date
- 2020
- Journal Title
- Scientific Reports
- ISSN
- 2045-2322
- Citation
- Scientific Reports vol. 10, no. 1
- Publisher
- Nature Research
- Indexed
- SCIE; SCOPUS
- Document Type
- Article
- Abstract
- 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. © 2020, The Author(s).
- DOI
- 10.1038/s41598-020-62550-6
- Appears in Collections:
- 자연과학대학 > 통계학전공 > Journal papers
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