Serum 25-hydroxyvitamin D and peripheral thyroid hormone sensitivity in euthyroid type 2 diabetes: Linear estimates and low-range threshold

Abstract

BACKGROUND

Vitamin D insufficiency is common in type 2 diabetes (T2D) and may relate to peripheral thyroid hormone sensitivity. We hypothesized that higher serum 25-hydroxyvitamin D [25(OH)D] is associated with a higher free triiodothyronine-to-free thyroxine ratio in euthyroid adults, with a nonlinear pattern.

AIM

To evaluate the association between serum 25(OH)D and the free triiodothyronine-to-free thyroxine ratio in euthyroid adults with T2D.

METHODS

We conducted a cross-sectional study in a real-world cohort from a metabolic management center in China. Euthyroid adults with T2D were enrolled (n = 1408). Free triiodothyronine, free thyroxine, thyroid-stimulating hormone, and 25(OH)D were measured at the same visit. Analyses of 25(OH)D were restricted to participants with available measurements (n = 1271). Multivariable linear regression modeled the ratio scaled by 100. Restricted cubic splines and two-piecewise models assessed nonlinearity and estimated a threshold. Prespecified subgroups included age, sex, body mass index, current smoking, and current drinking.

RESULTS

Higher 25(OH)D was associated with a higher scaled ratio in the fully adjusted model (β = 0.088 per 1 ng/mL; 95%CI: 0.037-0.139; P < 0.001), equivalent to +0.88 units per 10 ng/mL. Spline and segmented analyses indicated a low-range threshold at 14.7 ng/mL (95%CI: 12.85-16.11). The slope was steeper below the threshold and not significant above it. Estimates were numerically larger in participants aged ≥ 60 years, but age interaction was not significant (P for interaction = 0.113). A drinking interaction was observed: The association was positive in non-drinkers but null in current drinkers (P for interaction = 0.0115). Interaction testing was exploratory and not adjusted for multiple comparisons.

CONCLUSION

In euthyroid adults with T2D, higher 25(OH)D is associated with a higher free triiodothyronine-to-free thyroxine ratio, mainly at low 25(OH)D concentrations.

Keywords: 25-hydroxyvitamin D; Free triiodothyronine-to-free thyroxine ratio; Thyroid hormone sensitivity; Type 2 diabetes; Nonlinear association; Restricted cubic splines; Piecewise regression

Core Tip: In a real-world cohort of euthyroid adults with type 2 diabetes, we examined the association between serum 25-hydroxyvitamin D and the free triiodothyronine-to-free thyroxine (FT3/FT4) ratio, a pragmatic circulating proxy of peripheral thyroid hormone sensitivity. Using multivariable models with restricted cubic splines and segmented regression, we identified a low-range threshold around 14.7 ng/mL: The positive gradient was steeper below this level and was attenuated above it. The overall pattern was broadly consistent across prespecified subgroups, with attenuation among current drinkers. These findings are associative and require longitudinal or interventional confirmation.