Abstract
BACKGROUND: The association between circulating Vitamin D levels and the risk of major endocrine diseases remains insufficiently explored. Vitamin D may play a role in preventing the onset of various endocrine disorders, but the underlying mechanisms are still unclear.
METHODS: This study analyzed data from 62 985 participants in the UK Biobank and 19 518 participants in the UK Biobank Pharmaceutical Proteomics Project. Vitamin D concentrations were measured from blood samples collected between 2015 and 2017, with follow-up until 31 August 2022. We employed propensity score matching, Kaplan-Meier curves, multivariate Cox regression, and dose-response analyses to assess the relationship between circulating Vitamin D levels and the risk of major endocrine diseases. X-tile software was used to define Vitamin D deficiency thresholds. Additionally, we analyzed the relationship between Vitamin D-related circulating proteins and endocrine diseases using multivariate Cox and Spearman regressions.
RESULTS: Participants with sufficient Vitamin D levels had a lower risk of developing nontoxic single thyroid nodule [hazard ratio (HR) 0.55, 95% confidence interval (CI): 0.38-0.80], hyperparathyroidism (HR 0.45, 95% CI: 0.24-0.85), noninsulin-dependent diabetes mellitus (HR 0.69, 95% CI: 0.63-0.75), and hypercholesterolemia (HR 0.97, 95% CI: 0.89-1.00). Individuals with vitamin D levels above the threshold defined by X-tile still had a reduced risk of developing hyperthyroidism (HR 0.81, 95% CI: 0.71-0.93), nontoxic single thyroid nodule (HR 0.55, 95% CI: 0.38-0.80), hyperparathyroidism (HR 0.45, 95% CI: 0.32-0.63), insulin-dependent diabetes (HR 0.56, 95% CI: 0.38-0.84), and noninsulin-dependent diabetes mellitus (HR 0.70, 95% CI: 0.64-0.76). Restricted cubic splines showed a nonlinear relationship between Vitamin D levels and hypothyroidism, nontoxic thyroid nodule, and hypercholesterolemia ( P -nonlinearity 0.012, 0.044, <0.001). Of 1462 measured circulating proteins, 47 correlated significantly with Vitamin D levels (Spearman coefficient >0.1; P < 0.05), with interleukin-6 (IL-6) showing a specific interaction with major endocrine diseases.
CONCLUSION: The findings suggest that maintaining serum Vitamin D levels above 75 nmol/L reduces the risk of major endocrine diseases. The preventive effect of Vitamin D on endocrine diseases may be linked to its interaction with IL-6.