Association between circulating vitamin D levels and the risk of major endocrine diseases: insights from a longitudinal prospective cohort study

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 non-toxic single thyroid nodule (HR 0.55, 95% CI: 0.38-0.80), hyperparathyroidism (HR 0.45, 95% CI: 0.24-0.85), non-insulin dependent diabetes mellitus (HR 0.69, 95% CI: 0.63-0.75), and hypercholesterolemia (HR 0.97, 95% CI: 0.89-1.00). Using X-tile software to define Vitamin D deficiency thresholds, the risks for hyperthyroidism (HR 0.81, 95% CI: 0.71-0.93), non-toxic 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) decreased. Restricted cubic splines showed a nonlinear relationship between Vitamin D levels and hypothyroidism, non-toxic thyroid nodule, and hypercholesterolemia (P-nonlinearity 0.012, 0.044, < 0.001). Of 1,462 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 the Vitamin D receptor. Conclusion: The findings suggest that maintaining serum Vitamin D levels above 75 nmol/L reduce the risk of major endocrine diseases. The preventive effect of Vitamin D on endocrine diseases may be linked to its interaction with the IL-6.