Endocrinol Metab.  2021 Apr;36(2):436-446. 10.3803/EnM.2020.883.

High Serum-Induced AhRL Is Associated with Prevalent Metabolic Syndrome and Future Impairment of Glucose Tolerance in the Elderly

Affiliations
  • 1Department of Physiology, Kyung Hee University School of Medicine, Graduate School, Seoul, Korea
  • 2Department of Neuroscience, Medical Research Center for Bioreaction to Reactive Oxygen Species and Biomedical Science Institute, Kyung Hee University School of Medicine, Graduate School, Seoul, Korea
  • 3Department of Internal Medicine, Kangwon National University School of Medicine, Chuncheon, Korea
  • 4Occupational and Environmental Medicine, Uppsala University, Uppsala, Sweden
  • 5Acute and Internal Medicine, Department of Medicine, Uppsala University Hospital, Uppsala, Sweden
  • 6Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea

Abstract

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.

Keyword

Receptors; aryl hydrocarbon; Dioxins; Persistent organic pollutants; Metabolic syndrome; Glucose intolerance
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