The association between thyroid hormones and MAFLD is mediated by obesity and metabolic disorders and varies among MAFLD subtypes

Background Thyroid hormone (TH) disorders increased the risk of metabolic dysfunction-associated fatty liver disease (MAFLD). Aim To assess whether the association between TH and MAFLD is mediated via metabolic dysfunctions and varies among MAFLD subtypes (diabetes-MAFLD, overweight/obesity-MAFLD, metabolic disorders-MAFLD). Methods A total of 18,427 participants (661 diabetes-MAFLD, 3,600 overweight/obesity-MAFLD, 691 metabolic disorder-MAFLD cases, 13,475 non-MAFLD controls) from a Chinese hospital were enrolled. Hepatic ultrasound measurements and thyroid function were assessed. Results Overweight/obesity mediated the associations of MAFLD with triiodothyronine (T3), free triiodothyronine (FT3), free thyroxine (FT4), and the mediator accounted for 46.43%, 39.69%, and 42.68%, respectively. Metabolic disorder mediated the association of MAFLD with T3, FT3, FT4, thyroid stimulating hormone (TSH), and the mediator accounted for 36.57%, 23.19%, 34,65%, and 60.92%, respectively. Diabetes did not complementary mediate any association between TH and MAFLD. Elevated T3, FT3, TSH and decreased FT4 increased the risk of overweight/obesity-MAFLD, and the odds ratios were 1.59, 1.72, 1.18, and 0.60, respectively (Q4 vs.Q1, false discovery rate (FDR)<0.05). Elevated T3, FT3, and decreased FT4 increased the risk of metabolic disorder-MAFLD, and the odds ratios were 1.45, 1.33, and 0.52, respectively (Q4 vs.Q1, FDR<0.05). No significant association between TH and diabetes-MAFLD was detected. Conclusion The association between TH and MAFLD is mediated by overweight/obesity and metabolic disorders and varies among MAFLD subtypes.