Association between central thyroid hormone dysregulation and chronic kidney disease in type 2 diabetes: a cross-sectional study

Abstract

This cross-sectional study investigated the association between central thyroid hormone resistance and chronic kidney disease (CKD) in patients with type 2 diabetes mellitus (T2DM) who have normal peripheral thyroid hormones. The study included 2,759 T2DM patients with normal serum free triiodothyronine (FT3) and free thyroxine (FT4) levels. Central thyroid sensitivity was quantified using the Thyroid Feedback Quantile-based Index (TFQI), thyrotrophic thyroxine resistance index (TT4RI), TSH Index (TSHI), and FT3/FT4 ratio. Utilizing multivariable logistic regression and restricted cubic splines (RCS), we found that elevated TSH levels and increased central thyroid hormone resistance (indicated by higher TFQI, TT4RI, and TSHI) were independently associated with an increased risk of CKD. Notably, RCS analysis revealed a significant non-linear relationship (p < 0.001). Participants in the highest TSH quartile exhibited a 1.5-fold increased risk of CKD in multivariable regression (OR 1.50, 95% CI 1.08–2.07). Crucially, this association remained robust after propensity score-matched analyses (n = 684 pairs, OR 1.66, 95% CI 1.21–2.27). In conclusion, for T2DM patients with normal peripheral thyroid hormones, elevated TSH and reduced central thyroid hormone sensitivity are independently associated with a heightened risk of eGFR-defined CKD. These easily calculated indices may serve as valuable clinical biomarkers for early renal risk stratification.