Free Triiodothyronine and Free Triiodothyronine to Free Thyroxine Ratio Predict All-Cause Mortality in Patients with Diabetic Foot Ulcers

Jing Hong,1,&ast; Wen-Yue Liu,1,&ast; Xiang Hu,1 Wen-Wen Chen,2 Fei-Fei Jiang,1 Ze-Ru Xu,1 Fei-Xia Shen,1 Hong Zhu1 1Department of Endocrinology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000, People’s Republic of China; 2Department of Geriatrics, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Hong Zhu, Department of Endocrinology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, People’s Republic of China, Tel +86 577-55579622, Fax +86 577-55578522, Email zhuhong@wmu.edu.cnPurpose: Free triiodothyronine (FT3) and FT3/free thyroxine (FT4) ratio have been associated with mortality in various diseases. However, no study to date has identified a link between FT3, FT3/FT4 ratio and all-cause mortality in patients with diabetic foot ulcers (DFUs). This study aimed to investigate this relationship.Methods: This retrospective cohort study included 726 patients diagnosed with DFUs in a public hospital from January 2015 to October 2019. Patients were classified by the optimal cut-off values of the FT3 and FT3/FT4 ratio, respectively. The association of FT3 and FT3/FT4 ratio with all-cause mortality was evaluated in a multivariable cox regression model. Directed acyclic graphs were used to assess the minimally sufficient sets of confounding variables.Results: Log rank tests indicated that patients with low FT3 and FT3/FT4 ratio had lower overall survival rates (all p < 0.001). The adjusted HRs for all-cause mortality were 0.48 (95% CI: 0.32– 0.73, P = 0.001) when comparing high versus low FT3 and 0.47 (95% CI: 0.32– 0.70, P < 0.001) when comparing high versus low FT3/FT4 ratio. Subgroup analyses showed that these associations existed only in elderly patients (≥ 65 years) and women, after adjustment. In men, only high FT3/FT4 ratio was associated with low all-cause mortality