Correlation Between the Thyroid Hormone Levels and Type 2 Diabetes Mellitus in Non-Alcoholic Fatty Liver Disease

Liya Bian,1,* Hua Fan,2,* Qingwen Yu,1,* Xiyun Rao,1 Ting Tang,1 Lanlan Feng,1 Yongmin Yong Shi,1 Xuhan Tong,1 Xingwei Zhang,1 Jiake Tang,1 Pengwei Zhang,1 Mingwei Wang,1,3,4 Xianguo Qu5 1Department of Cardiology, The Affiliated Hospital of Hangzhou Normal University, Hangzhou Normal University, Hangzhou, Zhejiang, People’s Republic of China; 2School of Clinical Medicine, The First Affiliated Hospital of Henan University of Science and Technology, Luoyang, Henan, People’s Republic of China; 3Department of Cardiology, Hangzhou Lin’an Fourth People’s Hospital, Hangzhou, Zhejiang, People’s Republic of China; 4Department of Cardiology, Jiande First People’s Hospital, Hangzhou, Zhejiang, People’s Republic of China; 5Affiliated Hangzhou First People’s Hospital, School of Medicine, Westlake University, Hangzhou, Zhejiang, People’s Republic of China*These authors contributed equally to this workCorrespondence: Pengwei Zhang, Affiliated Hospital of Hangzhou Normal University, Hangzhou Normal University, No. 126, Wenzhou Road, Gongshu District, Hangzhou, Zhejiang, 310015, People’s Republic of China, Email [email protected] Mingwei Wang, Affiliated Hospital of Hangzhou Normal University, Hangzhou Normal University, No. 126, Wenzhou Road, Gongshu District, Hangzhou, Zhejiang, 310015, People’s Republic of China, Email [email protected]: Nonalcoholic fatty liver disease (NAFLD) and type 2 diabetes mellitus (T2DM) are significant metabolic disorders that frequently coexist and share interrelated pathophysiological mechanisms. Thyroid hormones (THs) play multifaceted roles in metabolic regulation. This study explored the association between THs—particularly the free triiodothyronine (FT3) to free thyroxine (FT4) ratio (FT3/FT4)—and T2DM among NAFLD individuals.Patients and Methods: A total of 4942 patients with NAFLD hospitalized at the Affiliated Hospital of Hangzhou Normal University between 2020 and 2023 were retrospectively analyzed. Partial correlation analysis controlling for age and sex was conducted to investigate the relationships between THs and the FT3/FT4 ratio with hemoglobin A1c (HbA1c) and fasting blood glucose (FBG) in NAFLD patients with T2DM. Meanwhile, the association between the FT3/FT4 ratio and T2DM was assessed by binary logistic regression. Receiver operating characteristic (ROC) curve analysis was performed to assess the discriminatory ability of the FT3/FT4 ratio for T2DM.Results: Patients with T2DM had significantly lower FT3, TT3, and the FT3/FT4 ratio, while higher FT4, compared with those without. Partial correlation analysis further showed the negative correlation of FT3, TT3, and the FT3/FT4 with HbA1c and FBG, with the FT3/FT4 ratio showing the strongest correlation with HbA1c (r = − 0.222, p < 0.001). After adjusting for confounding factors, individuals in the highest FT3/FT4 quartile had a markedly reduced likelihood of T2DM relative to those in the lowest quartile (OR 0.27, 95% CI 0.23– 0.33; p < 0.001). ROC analysis showed a moderate discriminatory performance of the FT3/FT4 ratio for T2DM (AUC up to 0.668).Conclusion: In patients with NAFLD, a lower FT3/FT4 ratio was significantly associated with T2DM and poorer glycemic status. Compared with individual TH levels, the FT3/FT4 ratio may serve as a more integrative marker of metabolic risk in this population. Keywords: nonalcoholic fatty liver disease, type 2 diabetes mellitus, FT3/FT4, hemoglobin A1c, fasting blood glucose