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

Area of Science:

• Nutritional Epidemiology
• Genetic Epidemiology
• Metabolic Disorders

Background:

• Inconsistent epidemiological evidence exists regarding the link between vitamin levels and diabetic complications.
• Understanding potential causal relationships is crucial for effective diabetes management and complication prevention.

Purpose of the Study:

• To investigate the causal associations between circulating vitamin levels (A, B6, C, D) and various diabetic complications using genetic variants.
• To provide robust genetic evidence to clarify the role of vitamins in the development of diabetic complications.

Main Methods:

• Utilized two-sample Mendelian randomization (MR) analyses with large-scale Genome-Wide Association Studies (GWAS) data for vitamin genetic variants (VitA, VitB6, VitC, VitD).
• Assessed associations with diabetic complications including maculopathy, ketoacidosis, hypoglycemia, neuropathy, nephropathy, and retinopathy.
• Employed multiple MR methods (IVW, weighted median, MR-Egger, MR-PRESSO) and conducted heterogeneity and sensitivity analyses.

Main Results:

• Inverse-variance weighted (IVW) analysis revealed a significant association between higher vitamin B6 (VitB6) levels and an increased risk of diabetic hypoglycemia (OR: 8.54; P=0.01).
• No significant causal associations were detected between vitamin A (VitA), vitamin C (VitC), or vitamin D (VitD) and the studied diabetic complications.
• Post-MR-PRESSO analysis confirmed no causal relationship between VitD and diabetic hypoglycemia, ketosis, or maculopathy.

Conclusions:

• Genetic evidence suggests that elevated vitamin B6 levels may be a risk factor for diabetic hypoglycemia.
• Vitamins A, C, and D do not appear to have a significant causal role in the development of common diabetic complications.
• Monitoring vitamin B6 levels and considering appropriate supplementation may be important for managing hypoglycemia risk, while other vitamins may have limited preventive effects.