School of Medicine, Xiamen University, Xiamen, China.
Xiamen Diabetes Institute, The First Affiliated Hospital of Xiamen University, Xiamen, China.
BMC Endocr Disord. 2022 Dec 12;22(1):313. doi: 10.1186/s12902-022-01228-8.
The severity of liver fibrosis is an important predictor of death in patients with non-alcoholic fatty liver disease (NAFLD) and type 2 diabetes mellitus (T2DM). However, there is still no definite conclusion on the relationship between triiodothyronine (T3) and the severity of liver fibrosis. Thus, the aim of this study was to analyze the correlation between T3 level and the severity of liver fibrosis.
We performed a cross-sectional study of 2072 T2DM patients with normal thyroid function from January 2017 to January 2020. NAFLD fibrosis score (NFS), Fibrosis index based on the 4 factors (FIB-4) and BARD score (BARD) were used to assess the severity of fibrosis in T2DM patients, and linear regression analyses were used to determine the factors independently associated with liver fibrosis. Further experiments were performed to assess the impact of low T3 on fibrosis progression in mice model and explore possible mechanisms.
Free triiodothyronine (fT3) levels had significantly inverse correlations with NFS and FIB-4, and BARD in T2DM patients (P < 0.05). In multiple linear regression analyses, decreased fT3 level was an independent risk factor for the severity of liver fibrosis of T2DM patients (P < 0.01). Findings from in-vivo experiment using mice model proved that hypothyroidism mice had more severe of liver fibrosis than those mice with normal thyroid function. We also found that T3 could inhibit the profibrotic TREM2CD9 macrophage, which had been identified an important player in the progression of liver fibrosis.
The findings from this study proved an inverse correlation between T3 level and the severity of liver fibrosis, and lower fT3 level within the normal range was an independent risk factor for severe liver fibrosis.
非酒精性脂肪性肝病（NAFLD）和 2 型糖尿病（T2DM）患者肝纤维化的严重程度是死亡的重要预测因素。然而，三碘甲状腺原氨酸（T3）与肝纤维化严重程度之间的关系仍没有明确的结论。因此，本研究旨在分析 T3 水平与肝纤维化严重程度的相关性。
我们对 2017 年 1 月至 2020 年 1 月期间 2072 例甲状腺功能正常的 T2DM 患者进行了横断面研究。采用 NAFLD 纤维化评分（NFS）、基于 4 项指标的纤维化指数（FIB-4）和 BARD 评分（BARD）评估 T2DM 患者的纤维化严重程度，采用线性回归分析确定与肝纤维化独立相关的因素。进一步实验评估了低 T3 对小鼠模型纤维化进展的影响，并探讨了可能的机制。
游离三碘甲状腺原氨酸（fT3）水平与 T2DM 患者的 NFS 和 FIB-4 以及 BARD 呈显著负相关（P<0.05）。在多元线性回归分析中，fT3 水平降低是 T2DM 患者肝纤维化严重程度的独立危险因素（P<0.01）。使用小鼠模型进行的体内实验结果表明，甲状腺功能减退小鼠的肝纤维化程度比甲状腺功能正常的小鼠更严重。我们还发现，T3 可以抑制促纤维化的 TREM2CD9 巨噬细胞，该细胞已被确定为肝纤维化进展的重要参与者。
本研究结果证明 T3 水平与肝纤维化严重程度呈负相关，正常范围内较低的 fT3 水平是严重肝纤维化的独立危险因素。
