Impaired Thyroid Hormone Sensitivity Linked to Increased Diabetic Nephropathy Risk in Euthyroid T2DM Patients: Study

"Higher values of thyroid feedback indices—PTFQI (OR 1.51), TFQI (OR 1.54), and TSHI—along with a lower FT3/FT4 ratio, were linked to greater DN risk," the researchers reported. "These hormonal alterations corresponded with elevated urinary albumin-to-creatinine ratio (UACR) and reduced estimated glomerular filtration rate (eGFR), indicating worsening kidney function."

Diabetes affects over 500 million people worldwide, with type 2 diabetes making up over 90% of cases. Diabetic nephropathy is a serious complication, often leading to kidney failure. Early signs are subtle, delaying diagnosis. While thyroid function is linked to DN, single hormone levels may not give the full picture—composite indices assessing thyroid hormone sensitivity may offer better insight into DN risk and progression.

Against the above background, Dengrong Ma, The First Clinical Medical College, Lanzhou University, Lanzhou, Gansu Province, People’s Republic of China, and colleagues aimed to explore the link between reduced thyroid hormone sensitivity and diabetic nephropathy in euthyroid individuals with type 2 diabetes mellitus (T2DM).

For this purpose, the researchers selected 1,305 euthyroid patients with T2DM who were hospitalized at the Endocrinology Department of the First Hospital of Lanzhou University between July 2021 and August 2023. Thyroid hormone sensitivity was assessed using several indices, including PTFQI, TFQI, TSHI, FT3/FT4 ratio, and TT4RI. Patients were divided into four groups based on the quartile levels of these indices. The association between thyroid hormone sensitivity and diabetic nephropathy (DN) was evaluated using binary logistic regression and restricted cubic spline (RCS) analysis.

The study revealed the following findings:

• PTFQI, TFQI, and TSHI levels were significantly higher in patients with diabetic nephropathy compared to those without DN.
• The FT3/FT4 ratio was notably lower in the DN group.
• Higher levels of PTFQI and TFQI were positively associated with an increased risk of DN, as confirmed by multivariate logistic regression analysis.
• Restricted cubic spline (RCS) analysis revealed a linear dose-response relationship between thyroid hormone sensitivity indices (PTFQI, TFQI, TSHI, FT3/FT4, and TT4RI) and the risk of DN.
• As PTFQI, TFQI, and TSHI levels increased and FT3/FT4 levels decreased, there was a corresponding rise in DN prevalence and urinary albumin-to-creatinine ratio (UACR).
• The estimated glomerular filtration rate (eGFR) declined with worsening thyroid hormone sensitivity, indicating a deterioration in kidney function.

In euthyroid patients with type 2 diabetes, impaired thyroid hormone sensitivity was found to be associated with diabetic nephropathy (DN), elevated UACR, and reduced eGFR. According to the authors, thyroid hormone sensitivity indices provide a more comprehensive evaluation of thyroid function than individual markers like TSH, FT3, or FT4.

The findings emphasize the importance of assessing thyroid hormone sensitivity in T2DM patients for the early detection and management of DN, even when conventional thyroid function tests are within normal ranges. The authors suggest that further research is warranted to better understand the mechanisms linking impaired thyroid hormone sensitivity with DN.

Reference:

Ma, D., Zhao, P., Gao, J., Guo, X., Han, M., Zan, X., … Liu, J. (2025). The Correlation Between Impaired Thyroid Hormone Sensitivity and Diabetic Nephropathy in Euthyroid Patients with Type 2 Diabetes Mellitus. Diabetes, Metabolic Syndrome and Obesity, 18, 1207–1221. https://doi.org/10.2147/DMSO.S507750