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The association between thyroid hormones and MAFLD is mediated by obesity and metabolic disorders and varies among
Hong Fan1, Lili Li2, Zhenqiu Liu3
1Department of Epidemiology, School of Public Health, Fudan University, Shanghai, China. Key Laboratory of Public Health Safety (Fudan University), Ministry of Education, China; Shanghai Institute of Infectious Disease and Biosecurity, School of Public Health, Fudan University, Shanghai, China; Fudan University Taizhou Institute of Health Sciences, Taizhou, China.
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.
Insights
Thyroid hormone levels influence metabolic dysfunction-associated fatty liver disease (MAFLD) risk, primarily through overweight/obesity and metabolic disorders. These pathways differ across MAFLD subtypes like diabetes and obesity.
Area of Science:
- Endocrinology
- Hepatology
- Metabolic Diseases
Background:
- Thyroid hormone (TH) disorders are linked to an increased risk of metabolic dysfunction-associated fatty liver disease (MAFLD).
- Understanding the mediating factors and subtype-specific associations is crucial for MAFLD management.
Purpose of the Study:
- To investigate if metabolic dysfunctions mediate the relationship between TH and MAFLD.
- To examine how this association varies across different MAFLD subtypes: diabetes-MAFLD, overweight/obesity-MAFLD, and metabolic disorders-MAFLD.
Main Methods:
- A cohort study involving 18,427 participants from a Chinese hospital.
- Assessment of hepatic ultrasound, thyroid function tests, and MAFLD classification into subtypes.
Main Results:
- Overweight/obesity significantly mediated MAFLD associations with triiodothyronine (T3), free triiodothyronine (FT3), and free thyroxine (FT4).
- Metabolic disorders mediated MAFLD associations with T3, FT3, FT4, and thyroid-stimulating hormone (TSH).
- Elevated T3 and FT3, and decreased FT4 were associated with increased risk in overweight/obesity-MAFLD and metabolic disorder-MAFLD subtypes.
Conclusions:
- The association between TH and MAFLD is mediated by overweight/obesity and metabolic disorders.
- These mediating pathways differ across MAFLD subtypes, with no significant TH association found for diabetes-MAFLD.
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