Causal Relationship Between Various Vitamins and Different Diabetic Complications: A Mendelian Randomization Study

Epidemiological evidence regarding the association between vitamins and diabetic complications remains inconsistent. This study aims to explore the potential causal relationships between diabetic complications and circulating vitamins in diabetics. We selected vitamin A (VitA) genetic variants (n = 5,006), vitamin B₆ (VitB₆) genetic variants (n = 64,974), vitamin C (VitC) genetic variants (n = 52,018) and vitamin D (VitD) genetic variants (n = 441,291) as exposures of interest from large-scale Genome-Wide Association Studies (GWAS) databases. Then we performed two-sample Mendelian randomization (MR) analyses to evaluate the causal association of plasma vitamin levels with diabetic complications, which included maculopathy, ketoacidosis, hypoglycemia, neuropathy, nephropathy and retinopathy. Multiple methods were performed and used including the inverse-variance weighted (IVW), the weighted median, MR-Egger and MR-PRESSO regression. Heterogeneity and sensitivity analyses were conducted. The results of the IVW method revealed that the level of VitB₆ were associated with diabetic hypoglycemia with (OR: 8.54; 95% CI: 1.77 to 41.2; p: 0.01). No association was detected between other vitamins (VitA, VitC or VitD) and diabetic complications (maculopathy, ketoacidosis, hypoglycemia, neuropathy, nephropathy or retinopathy). After MR-PRESSO analysis, there was no causal relationship detected between VitD and diabetic hypoglycemia (OR: 0.867, CI: 0.64 to 1.18, p: 0.37), diabetic ketosis (OR: 0.763515, CI: 0.58 to 1.00, p: 0.055), diabetic maculopathy (OR: 0.72, CI: 0.48 to 1.07, p: 0.105). This analysis provided genetic evidence that the level of VitB₆ may be the risk factor for diabetic hypoglycemia. VitA, VitC, or VitD were not associated with various diabetic complications. Monitoring for excess VitB₆ and suitable supplements might be important, and other vitamins may have limited effects in complications prevention, and further investigations were needed to unveil the mechanisms.