Association between vitamin D level and risk of type 2 diabetes: a systematic review of Mendelian Randomization studies

This study aims to review the evidence from Mendelian randomization (MR) studies on the causal role of vitamin D in type 2 diabetes (T2D). A systematic search (registered on PROSPERO (CRD42024551731)) was performed in PubMed, Embase and Web of Science for publications up to June 2024. MR studies including vitamin D as the exposure and T2D as the outcome were included. Among the 22 studies included, which were mainly in European populations, half used single nucleotide polymorphisms (SNPs) located on vitamin D synthesis and metabolism genes, while others selected SNPs based on statistical thresholds. Negative associations implying that vitamin D protects against T2D were reported in three one-sample and three two-sample MR studies. The remaining studies reported null associations between genetically predicted circulating 25-hydroxyvitamin D and risk of T2D regardless of MR design, study population, data source or SNP selection. Findings from MR studies on circulating 25-hydroxyvitamin D and risk of T2D do not consistently support the causal role of vitamin D in T2D in the general population. Future MR studies to examine the non-linear association of vitamin D with T2D or disease progression from prediabetes are warranted to clarify the use of vitamin D in the prevention of T2D.