Abstract
BACKGROUND: Evidence is limited and inconsistent regarding vitamin D and heart failure (HF) risk in people with type 2 diabetes (T2D), among whom vitamin D insufficiency or deficiency is common.</p>
OBJECTIVE: This study aimed to investigate the associations of serum 25-hydroxyvitamin D (25[OH]D) with HF risk among individuals with T2D, in observational and Mendelian randomization (MR) frameworks.</p>
METHODS: Observational analyses were performed among 15,226 T2D participants aged 40-72 from the UK Biobank. HF incidence was ascertained through electronic health records. Cox proportional hazard regression models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for the association between serum 25(OH)D and HF risk among people with T2D. MR analyses were conducted among 11,260 unrelated participants with T2D. A weighted genetic risk score (GRS) for genetically predicted 25(OH)D concentration was instrumented using 62 confirmed genome-wide variants.</p>
RESULTS: The mean ± standard deviation of serum 25(OH)D was 43.4 ± 20.4 nmol/L. During a median follow-up of 11.3 years, 836 incident HF events occurred. Serum 25(OH)D was nonlinearly and inversely associated with HF and the decreasing risk tended to plateau at around 50 nmol/L. Comparing those with 25(OH)D <25 nmol/L, the multivariable-adjusted HR (95% CI) was 0.67 (0.54, 0.83) for participants with 25(OH)D of 50.0-74.9 nmol/L and was 0.71 (0.52, 0.98) for 25(OH)D >75 nmol/L. In MR analysis, each 7% increment in genetically predicted 25(OH)D was associated with 36% lower risk of HF among people with T2D (HR: 0.64, 95% CI: 0.41, 0.99).</p>
CONCLUSIONS/INTERPRETATION: Higher serum 25(OH)D was associated with lower HF risk among individuals with T2D and the MR analysis suggested a potential causal relationship. These findings indicate a role of maintaining adequate vitamin D status in the prevention of HF among individuals with T2D.</p>