Mediating role of triglyceride-glucose index and its derivatives in the relationship between central obesity and Hashimoto thyroiditis in type 2 diabetes

Background: Obesity and insulin resistance (IR) may be risk factors for thyroid disease, but there is no clinical-based consensus on this topic. Therefore, this study aims to evaluate the associations between the triglyceride-glucose index (TyG) and its derivatives and Hashimoto thyroiditis (HT) in type 2 diabetes mellitus (T2DM) patients, and explore the relationships between the central obesity indicators and HT risk to provide a reliable basis for the early prevention of HT.

Methods: A total of 1071 T2DM patients aged ≥ 20 years were selected from a tertiary hospital in Tianjin, all of them had normal thyroid function (including free triiodothyronine, free thyroxine, total triiodothyronine, total thyroxine, and thyroid-stimulating hormone). HT was assessed via thyroid-associated antibodies and thyroid colour Doppler ultrasound. TyG and its derivatives were measured via IR. Restricted cubic spline (RCS) models, multivariable logistic regression, and receiver operating characteristic (ROC) curve analysis were used to explore the correlations and predict HT. Mediation analysis explored the mediating role of TyG and its derivatives in the associations between the central obesity indicators and HT.

Results: RCS models revealed that increases in waist circumference (WC), waist-to-height ratio (WHtR), waist-to-hip ratio (WHR), TyG-WC, TyG-WHR, and TyG-WHtR were associated with increased HT risk. Logistic regression revealed that participants in the fourth quartile of TyG-WC, TyG-WHR, and TyG-WHtR had approximately 3.38 times greater HT risk (odds ratio range: 2.807 to 3.375). ROC analysis revealed that WC, WHtR, WHR, TyG-WC, TyG-WHtR and TyG-WHtR could distinguish the presence of HT. In females, the WHR had the highest predictive power, with an area under the ROC curve of 0.651 (95% confidence interval 0.611-0.691, P < 0.001). Mediation analysis revealed that high IR, as assessed by the TyG-body mass index (TyG-BMI), significantly mediated the effects of WC, WHtR, and WHR on the risk of HT. Among them, the TyG-BMI had the highest proportion of mediating effect of WC on HT risk, reaching 74.08%.

Conclusion: IR significantly mediates the increased risk of HT associated with central obesity. In clinical practice, WC, WHtR, WHR, TyG-WC, TyG-WHR, and TyG-WHtR serve as sensitive indicators for predicting HT risk in adult T2DM patients.