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 Koreaopen access
- 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
- Issue Date
- Apr-2020
- Publisher
- NATURE PUBLISHING GROUP
- Citation
- SCIENTIFIC REPORTS, v.10, no.1
- Journal Title
- SCIENTIFIC REPORTS
- Volume
- 10
- Number
- 1
- URI
- https://scholarworks.bwise.kr/cau/handle/2019.sw.cau/69901
- DOI
- 10.1038/s41598-020-62550-6
- ISSN
- 2045-2322
- 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.
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