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

Abstract

Purpose

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, after adjustment.

Conclusion

Routine assessment of FT3 and FT3/FT4 ratio may be a simple and effective way to identify high-risk patients with DFUs, especially in elderly patients and women.

Keywords:

• FT3
• FT3/FT4 ratio
• mortality
• diabetic foot ulcer

Abbreviations

DFUs, diabetic foot ulcers; T3, triiodothyronine; FT3, free triiodothyronine; T4, thyroxine; FT4, free thyroxine; TSH, thyroid-stimulating hormone; SBP, systolic blood pressure; DBP, diastolic blood pressure; HDL, high-density lipoprotein; LDL, low-density lipoprotein; TC, total cholesterol; TG, triglyceride; HbA1c, hemoglobin A1c; ALB, albumin; Hb, hemoglobin; eGFR, estimated glomerular filtration rate; OS, overall survival; DAG, directed acyclic graph; ROC, receiver operating characteristic; AUC, area under ROC curve; Ref, Reference.

Data Sharing Statement

The datasets used and analysed during the current study are available from the corresponding author on reasonable request.

Ethics Approval and Consent to Participate

The study protocol was approved by the ethics committee of the First Affiliated Hospital of Wenzhou Medical University (approval number: 2018-105). The data of patients accessed were anonymized and maintained with confidentiality. Due to the retrospective nature of the study, not compromising the privacy of patients, the requirement for informed consent was waived. This study was performed in accordance with the Declaration of Helsinki as revised in 2013.

Acknowledgments

The authors like to acknowledge all the patients who participated in the study.

Disclosure

The authors have no conflicts of interest to disclose.

Additional information

Funding

This study was supported by the Natural Science Foundation of China (81900737), the Basic Scientific Research Program of Wenzhou Medical University, China (KYYW202015).