Vitamin D, Prediabetes, and Diabetes—Bidirectional Mendelian Randomization Analysis

Abstract

Background: Vitamin D deficiency is associated with diabetes in many observational studies. However, the causality between them has not been established. We used bi-directional mendelian randomization (MR) analysis to explore the causal relationship between 25-hydroxyvitamin D [25(OH)D] and glycemic status and indices. Methods: Participants were included from a survey in East China from 2014-2016 (10,338 and 10,655 participants having diabetes and vitamin D related genotyping information). We calculated weighted genetic risk scores (GRS) as the instrumental variables for 25(OH)D concentration and diabetes based on related single nucleotide polymorphisms. Fasting plasma glucose and HbA1c were measured. Diagnosis of diabetes and prediabetes was based on American Diabetes Association criteria. Results: The MR-derived odds ratios of genetically determined 25(OH)D for risk of diabetes and prediabetes was 0.985 (95% CI 0.940, 1.032) and 0.982 (95% CI 0.948, 1.016), respectively. The MR-derived estimates for fasting plasma glucose and HbA1c were also not significant. Conversely, the MR-derived regression coefficients of genetically determined diabetes and prediabetes for 25(OH)D was 0.448 (95% CI -0.395, 1.291) and 1.303 (95% CI -1.210, 3.816). Conclusion: Our results support the conclusion that there is no causal association between vitamin D and diabetes and prediabetes using a bi-directional MR approach in a Chinese population. MR studies using 1,25-dihydroxyvitamin D and large intervention trials are needed to further validate the findings. Disclosure N. Wang: None. L. Zhao: None. C. Chen: None. Y. Chen: None. Y. Lu: None.