Intermittent fasting-induced amelioration of thyroid hormone sensitivity was associated with improvements in insulin sensitivity independent of weight loss in steatotic liver disease

Aim: This study aimed to evaluate the effect of the intermittent fasting (IF) intervention on metabolism and thyroid hormone sensitivity (THS) in patients with steatotic liver disease (SLD) and to further investigate the association between changes in THS and alterations in metabolic parameters during the intervention. Methods: A total of 78 patients with SLD underwent a 5:2 IF intervention for 8 weeks. Metabolic outcomes and THS, measured by the thyroid feedback quantile-based index (TFQI), thyrotroph thyroxine resistance index, thyroid-stimulating hormone index (TSHI), and free triiodothyronine to free thyroxine ratio (FT3/FT4), were assessed at baseline and after the intervention. Multiple regression analysis was performed to examine relationships between changes in THS and metabolic parameters during the intervention. Results: Average hepatic fat content was 15.02% at baseline and decreased by 3.79% after the 8-week IF intervention, accompanied by significant reductions in body weight, blood glucose, serum lipids, fasting insulin, homeostatic model assessment of insulin resistance (HOMA-IR), and adipose tissue insulin resistance index (Adipo-IR). After the intervention, THS improved: TFQI, thyrotroph thyroxine resistance index, and TSHI all decreased, while FT3/FT4 increased. Significant positive correlations were observed between ΔTFQI and ΔTSHI and changes in fasting insulin, HOMA-IR, and Adipo-IR. In multivariate models adjusted for age, sex, and weight loss, ΔTFQI and ΔTSHI remained significantly correlated with Δinsulin, ΔHOMA-IR, and ΔAdipo-IR. Conclusion: IF-induced improvement in THS was associated with enhanced insulin sensitivity independent of weight loss in patients with SLD. These findings suggest that THS may play a role in metabolic improvements and could inform therapeutic strategies for SLD.