Prognostic Role of TSH Within Euthyroid T2DM Patients with Retinopathy: A 3-Year Cohort Study

Abstract

Background/objectives: We aimed to determine how baseline TSH levels relate to clinical outcomes over a three-year follow-up in euthyroid patients with T2DR.

Methods: This single-center retrospective cohort study included 363 euthyroid T2DR patients who were followed for three years after baseline TSH measurement. Patients were stratified into tertiles based on TSH values belonging to the standard clinical limits (0.35-4.50 mIU/L). Binary and multivariate logistic regression analyses, along with non-linear modeling, were used to evaluate the prognostic impact of TSH and its interaction with age on mortality. The study adhered to the STROBE guidelines.

Results: In the first year of follow-up, Group 1 (TSH 0.35-1.24 mIU/L) had significantly higher rates of mortality and combined outcomes compared to Group 2 (TSH 1.24-1.94 mIU/L; p = 0.025 and p = 0.041, respectively). Group 2 had a lower risk (OR for mortality = 0.349, p = 0.004; OR for combined outcome = 0.358, p = 0.007). Between TSH and TSH tertiles, a non-linear, inverted U-shaped relationship was observed, with the lowest mortality risk near 2.0 mIU/L. A significant interaction between TSH and age was found for third-year mortality (p = 0.016).

Conclusions: TSH values showed a non-linear association with outcomes in euthyroid T2DR patients. Group 2 was linked to the lowest risk. Given the significantly higher mortality and combined complications identified within Group 1, closer monitoring and individualized follow-up strategies may be warranted for these patients. Additionally, TSH's impact on long-term mortality increased with age, supporting its use alongside age for risk stratification in T2DR.

Keywords: hormonal biomarkers; non-linear association; risk stratification; short-term prognosis; thyrotropin reference range.

Figure 1

Distribution of TSH levels across tertile groups. Box plots are used to visually represent the median, interquartile range, and full range. A statistically significant difference was observed between the groups (p < 0.001, Kruskal–Wallis test); TSH: thyroid-stimulating hormone; mIU/L: milli-international units per liter.

Figure 2

Inverse U-shaped correlation observed with serum TSH levels and one-year mortality risk, X-axis: TSH levels; Y-axis: mortality risk (predicted probability); blue line: predicted mortality risk across TSH levels; red dashed line: optimal TSH level where mortality risk is lowest, gray-shaded area: TSH Group 2 (1.24–1.94 mIU/L).

Figure 3

Age-stratified 3–year mortality rates across TSH tertile groups. Intermediate TSH levels (Group 2: 1.24–1.94 mIU/L) were consistently associated with lower mortality across all age strata.