Abstract
BACKGROUND: In several observational studies, vitamins B6, B9, B12, C and 25-hydroxyvitamin D[25(OH)D] concentrations were associated with type 2 diabetes mellitus (T2DM). Although vitamins play a role in the development of type 2 diabetes mellitus (T2DM), their associations remain unclear.
OBJECTIVE: This study employed Mendelian randomisation (MR) to explore the causal relationships between circulating concentrations of vitamins B6, B9, B12, C, 25-hydroxyvitamin D and T2DM.
METHODS: Single-nucleotide polymorphisms (SNPs) linked to vitamin B6, vitamin B9, vitamin B12, vitamin C and 25(OH)D levels were used as instrumental variables (IVs) in this study. We have two outcomes related to T2DM derived from two genome-wide association studies (GWAS). The first study, referenced by PMID: 3417140, encompasses a cohort of 406,831 individuals of European descent. The second study, identified by PMID: 29892013, includes a sample size of 468,298 Europeans.
RESULTS: Both univariable Mendelian randomization (UVMR) and multivariable Mendelian randomization (MVMR) analyses demonstrate that genetically predicted elevated levels of serum 25(OH)D are consistently associated with a reduced risk of T2DM. In the UVMR analyses, A 1-SD increase in genetically predicted serum 25(OH)D levels, the inverse-variance weighted (IVW) p = 3.8 × 10-7, pfdr = 7.6 × 10-7, the odds ratio(OR) of T2DM (GCST90013942) was 0.67, 95% confidence interval (CI): 0.57-0.78. Furthermore, a 1-SD increase in genetically predicted serum 25(OH)D levels was associated with an OR of 0.987 for T2DM (GCST90029024), the IVW p = 1.1 × 10-4, pfdr = 1.1 × 10-4 with a 95% CI of 0.981-0.994. In the MVMR analyses, genetically predicted higher serum 25(OH)D levels were associated with a decreased risk of T2DM by the IVW p = 1.2 × 10-5, pfdr = 5.9 × 10-5 in GCST90013942 and IVW p = 4.9 × 10-4, pfdr = 2.5 × 10-3 in GCST90029024. In contrast, levels of vitamins B6, B9, B12, and C did not domenstrate a significant association with T2DM.
CONCLUSION: Our research reveals that higher circulating serum 25(OH)D levels reduce the possibility of T2DM.