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Original Article
Clinical Study
High Serum-Induced AhRL Is Associated with Prevalent Metabolic Syndrome and Future Impairment of Glucose Tolerance in the Elderly
Youngmi Kim Pak, Hoon Sung Choi, Wook Ha Park, Suyeol Im, P. Monica Lind, Lars Lind, Hong Kyu Lee
Endocrinol Metab. 2021;36(2):436-446.   Published online April 19, 2021
DOI: https://doi.org/10.3803/EnM.2020.883
  • 3,781 View
  • 108 Download
  • 2 Web of Science
  • 2 Crossref
AbstractAbstract PDFSupplementary MaterialPubReader   ePub   
Background
High circulating levels of dioxins and dioxin-like chemicals, acting via the aryl hydrocarbon receptor (AhR), have previously been linked to diabetes. We now investigated whether the serum AhR ligands (AhRL) were higher in subjects with metabolic syndrome (MetS) and in subjects who had developed a worsened glucose tolerance over time.
Methods
Serum AhRL at baseline was measured by a cell-based AhRL activity assay in 70-year-old subjects (n=911) in the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) study. The main outcome measures were prevalent MetS and worsening of glucose tolerance over 5 years of follow-up.
Results
AhRL was significantly elevated in subjects with prevalent MetS as compared to those without MetS, following adjustment for sex, smoking, exercise habits, alcohol intake and educational level (P=0.009). AhRL at baseline was higher in subjects who developed impaired fasting glucose or diabetes at age 75 years than in those who remained normoglycemic (P=0.0081). The odds ratio (OR) of AhRL for worsening glucose tolerance over 5 years was 1.43 (95% confidence interval [CI], 1.13 to 1.81; P=0.003, continuous variables) and 2.81 (95% CI, 1.31 to 6.02; P=0.008, in the highest quartile) adjusted for sex, life style factors, body mass index, and glucose.
Conclusion
These findings support a large body of epidemiologic evidence that exposure to AhR transactivating substances, such as dioxins and dioxin-like chemicals, might be involved in the pathogenesis of MetS and diabetes development. Measurement of serum AhRL in humans can be a useful tool in predicting the onset of metabolic disorders.

Citations

Citations to this article as recorded by  
  • An Interactive Online App for Predicting Diabetes via Machine Learning from Environment-Polluting Chemical Exposure Data
    Rosy Oh, Hong Kyu Lee, Youngmi Kim Pak, Man-Suk Oh
    International Journal of Environmental Research and Public Health.2022; 19(10): 5800.     CrossRef
  • A Novel Aryl Hydrocarbon Receptor Antagonist HBU651 Ameliorates Peripheral and Hypothalamic Inflammation in High-Fat Diet-Induced Obese Mice
    Sora Kang, Aden Geonhee Lee, Suyeol Im, Seung Jun Oh, Hye Ji Yoon, Jeong Ho Park, Youngmi Kim Pak
    International Journal of Molecular Sciences.2022; 23(23): 14871.     CrossRef
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Review Article
Miscellaneous
Evidence of the Possible Harm of Endocrine-Disrupting Chemicals in Humans: Ongoing Debates and Key Issues
Duk-Hee Lee
Endocrinol Metab. 2018;33(1):44-52.   Published online March 21, 2018
DOI: https://doi.org/10.3803/EnM.2018.33.1.44
  • 9,903 View
  • 132 Download
  • 43 Web of Science
  • 44 Crossref
AbstractAbstract PDFPubReader   ePub   

Evidence has emerged that endocrine-disrupting chemicals (EDCs) can produce adverse effects, even at low doses that are assumed safe. However, systemic reviews and meta-analyses focusing on human studies, especially of EDCs with short half-lives, have demonstrated inconsistent results. Epidemiological studies have insuperable methodological limitations, including the unpredictable net effects of mixtures, non-monotonic dose-response relationships, the non-existence of unexposed groups, and the low reliability of exposure assessment. Thus, despite increases in EDC-linked diseases, traditional epidemiological studies based on individual measurements of EDCs in bio-specimens may fail to provide consistent results. The exposome has been suggested as a promising approach to address the uncertainties surrounding human studies, but it is never free from these methodological issues. Although exposure to EDCs during critical developmental periods is a major concern, continuous exposure to EDCs during non-critical periods is also harmful. Indeed, the evolutionary aspects of epigenetic programming triggered by EDCs during development should be considered because it is a key mechanism for developmental plasticity. Presently, living without EDCs is impossible due to their omnipresence. Importantly, there are lifestyles which can increase the excretion of EDCs or mitigate their harmful effects through the activation of mitohormesis or xenohormesis. Effectiveness of lifestyle interventions should be evaluated as practical ways against EDCs in the real world.

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Endocrinol Metab : Endocrinology and Metabolism