Thyroid Hormone Indices and Histopathological Severity of Diabetic Nephropathy in Euthyroid Patients with Type 2...

Thyroid hormones (THs) influence glucose homeostasis, vascular tone, and renal hemodynamics. Whether subtle variations in TH indices within the euthyroid range are associated with histopathological severity of diabetic nephropathy (DN) is unclear. We examined the association between TH indices and renal pathological severity in euthyroid patients with type 2 diabetes mellitus (T₂DM) and biopsy-proven DN.

In this single-center cross-sectional study, 362 euthyroid adults with T₂DM and biopsy-confirmed DN were included. DN lesions were classified according to the Renal Pathology Society classification as early (class I-II) or advanced (class III-IV). Serum free triiodothyronine (FT3), free thyroxine (FT4), thyroid-stimulating hormone (TSH), and the FT3/FT4 ratio were measured. Multivariable logistic regression and restricted cubic splines (RCS) were used to evaluate associations with advanced DN.

Of 362 patients, 143 had early DN and 219 had advanced DN. Compared with the early DN group, patients with advanced DN had lower FT3 levels (4.46 ± 0.66 vs 4.82 ± 0.73 pmol/L, P < 0.001) and a lower FT3/FT4 ratio (median 0.31 vs 0.33, P = 0.013). In fully adjusted models, lower FT3 levels were independently associated with higher odds of advanced DN (OR = 0.442, 95% CI 0.293-0.666, P < 0.001). In sensitivity analyses with further adjustment for estimated glomerular filtration rate (eGFR) and diabetic retinopathy, the inverse association between the FT3/FT4 ratio and advanced DN was attenuated and became borderline significant, whereas the association for FT3 remained robust. Moreover, higher FT3 quartiles were associated with progressively lower odds of advanced DN (Q4 vs Q1: OR = 0.160, 95% CI 0.070-0.365; P for trend < 0.001). RCS and quartile analyses suggested a predominantly linear inverse association between FT3 and the probability of advanced DN, with a similar but weaker pattern observed for the FT3/FT4 ratio.

Our findings extend prior studies based on eGFR or albuminuria by providing biopsy-confirmed histopathological evidence linking low-normal THs to the structural severity of DN. These results suggest that subtle reductions in peripheral T3 activity may be associated with underlying renal injury and could have potential value in identifying patients at higher risk.