Association of Phthalate Exposure with Thyroid Function and Thyroid Homeostasis Parameters in Type 2 Diabetes

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.

Iodine Deficiency, Maternal Hypothyroxinemia and Endocrine Disrupters Affecting Fetal Brain Development: A Scoping Review

“…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-pituitary-thyroid axis, and changing NIS-mediated iodide uptake, iodothyronine deiodinases, or hepatic enzymes [ 102 , 168 ].…”

“…From observational studies, there is strong evidence that TDCs are disturbing the thyroid hormone metabolism (s. Table 2 ). This is reported for several classes of TDCs, for mother-child pairs, in case controls, smaller cohorts or larger epidemiological studies [ 6 , 102 , 135 , 136 , 137 , 138 , 139 , 140 , 141 , 142 , 143 , 144 , 145 , 146 , 147 , 148 , 149 , 150 , 151 , 152 , 153 , 154 , 155 , 156 , 157 , 158 , 159 , 160 , 161 , 162 , 163 , 164 , 165 , 166 , 167 , 168 , 169 , 170 , 171 , 172 , 173 , 174 , 175 , 176 , 177 , 178 , 179 , 180 , 18...…”

“…The available evidence suggests that intrauterine PM 2.5 exposure can alter prenatal brain development through oxidative stress and systemic inflammation, leading to chronic neuroinflammation, microglial activation, and neuronal micturition disorder [ 18 , 168 , 246 ]. It has been shown that particulate matter exposure during fetal lifetime was associated with structural changes in the child’s cerebral cortex, as well as with impairment of essential executive functions, such as inhibitory control [ 247 , 248 ].…”

“…This is reported for several classes of TDCs, for mother-child pairs, in case controls, smaller cohorts or larger epidemiological studies [6,102,. However, further research and long-term clinical studies are necessary to finally elaborate on the dose-related associations [6,168,227,229,[233][234][235][236].…”

Differential expression of serum mir-363-3p in patients with polycystic ovary syndrome and its predictive value for their pregnancy

“…The FBG level of PCOS patients is generally higher than that of the control group. Long-term high-level of FBG can make the blood insulin content increase continuously, thus inducing hyperinsulinemia, further inducing insulin resistance, and ultimately inducing the disorder of glucose metabolism and reproductive hormones [ 23 ]. Presently, the correlation between miR-363-3p and insulin resistance has only been verified in animal experiments.…”