Baseline 25-Hydroxyvitamin D as a Stronger Protector Against Type 2 Diabetes in the Context of Hyperuricemia and Gout: A Cohort Study Based on the UK Biobank.

Abstract

Background: To elucidate the association between Vitamin D and the risk of Type 2 diabetes (T2D) in individuals with hyperuricemia or gout.

Methods: A total of 43731 patients with hyperuricemia and 9695 with gout were included to assess the association between Vitamin D levels and T2D risk. Serum 25(OH)D (nmol/L) concentrations were measured. Multivariable logistic regression, cumulative incidence curves, Cox proportional-hazards models, and restricted cubic spline analysis were used to evaluate the relationship between 25(OH)D and T2D risk. Sensitivity and stratified analyses were performed to ensure the robustness of the findings.

Results: Higher serum 25(OH)D concentration was associated with lower risk of baseline T2D. During a median follow-up of 14.27 years for hyperuricemia patients and 14.09 years for gout patients, 4617 and 1072 new-onset T2D cases were documented, respectively. An inverse, nonlinear dose-response relationship was found between 25(OH)D and incident T2D in hyperuricemia patients. Compared to participants with 25(OH)D < 25 nmol/L, the adjusted HR for those with 25(OH)D > 75 nmol/L was 0.62 (0.54, 0.72). In gout patients, the protective effect of 25(OH)D was even more pronounced [HR: 0.45(0.32, 0.62)]. Sensitivity analyses confirmed the robustness of our findings. Significant interactions were observed with age, smoking, and cardiovascular disease, while genetic susceptibility showed no interaction. The protective effect of 25(OH)D (per 10 nmol/L increase) was stronger in hyperuricemia patients aged <65 years [<65 years: 0.91 (0.89, 0.93), ≥65 years 0.96 (0.93, 0.99)] and in never smokers [Never: 0.92 (0.89, 0.95), Current: 1.00 (0.95, 1.06)]. Among gout patients, the effect was more evident in those without cardiovascular disease [No: 0.86 (0.82, 0.90), Yes: 0.92 (0.84, 1.00)].

Conclusions: Higher serum 25(OH)D concentration is significantly associated with a lower risk of incident T2D in patients with hyperuricemia or gout, and this association is especially pronounced among younger individuals, non-smokers and those without cardiovascular disease.