Abstract
Aims Phthalates, which are recognized environmental endocrine-disrupting chemicals, are associated with thyroid hormone disruption. We aimed to evaluate the relationship of phthalate metabolites with thyroid function and thyroid homeostasis parameters in type 2 diabetes and to explore whether thyroid autoimmunity status and metformin, the most common antidiabetic drug, may influence such associations. Methods Concurrent urine and blood samples were collected from 639 participants with type 2 diabetes in the METAL (Environmental Pollutant Exposure and Metabolic Diseases in Shanghai) study. We measured urinary concentrations of thirteen phthalate metabolites along with serum levels of thyroid-stimulating hormone (TSH), total T4 and T3, free T4 (FT4) and T3 (FT3), thyroid peroxidase antibody (TPOAb), and thyroglobulin antibody (TgAb). Four parameters of thyroid homeostasis, including the sum activity of step-up deiodinases (SPINA-GD), thyroid secretory capacity (SPINA-GT), Jostel's TSH index (TSHI), and thyrotroph thyroid hormone resistance index (TTSI), were also calculated. Results Among all participants, after full adjustment, multivariable regression analysis showed that some urine phthalate metabolites were negatively associated with TSH, TSHI, and TTSI levels and positively associated with FT3, T3, SPINA-GD, and SPINA-GT levels. None of the urine phthalate metabolites exhibited a significant association with thyroid autoimmunity. The associations of phthalate metabolites with thyroid function and thyroid homeostasis parameters differed based on thyroid autoantibody and metformin treatment status. Conclusions Urinary phthalate metabolites may be associated with thyroid function and thyroid homeostasis parameters among participants with type 2 diabetes. Furthermore, our present study suggested that thyroid autoantibody status and metformin treatment status are potential mediators of such associations.
Highlights
Phthalates, a group of similar diesters of phthalic acid, are ubiquitous in different environmental exposure media around the world
We evaluated the relationship of thirteen phthalate metabolites with thyroid function variables (TSH, FT3, free T4 (FT4), T3, and T4) and thyroid homeostasis parameters (SPINA-GD, SPINA-GT, TSH index (TSHI), and thyrotroph thyroid hormone resistance index (TTSI)) among participants with type 2 diabetes in the METAL study (2018) in Shanghai, China
We found that some of the urine phthalate metabolites were negatively associated with thyroid-stimulating hormone (TSH), TSHI, and TTSI levels and positively associated with FT3, T3, SPINA-GD, and SPINA-GT levels
Summary
Phthalates, a group of similar diesters of phthalic acid, are ubiquitous in different environmental exposure media around the world. Human exposure to phthalates mainly occurs through food due to their use during food production, processing, and packaging [1, 2]. Studies have demonstrated that thyroid-stimulating hormone (TSH) levels within the reference range were associated with neurocognitive problems [9], obesity, lipid profile, insulin resistance, and other risk factors for cardiovascular diseases [10, 11]. The literature has reported associations between different phthalate metabolites and thyroid hormone levels in both children and adults with inconsistent results [12,13,14]. Animal studies have indicated that phthalates alter thyroid signaling through a number of potential mechanisms, including interference with the TSH receptor, binding to transport proteins, interfering with the hypothalamic-pituitarythyroid axis, and changing sodium-iodide symportermediated iodide uptake, iodothyronine deiodinases, or hepatic enzymes [12, 15,16,17,18,19]
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