Bidirectional association between diabetic peripheral neuropathy and vitamin B12 deficiency: Two longitudinal 9-year follow-up studies using a national sample cohort

Aim: This study aims to investigate the association among metformin use, vit B12 deficiency, and DPN occurrence in diabetes. Methods: This retrospective, propensity-matched cohort study was performed using National Health Insurance Service database - National Sample Cohort in South Korea. Study 1 analyzed DPN incidence according to vit B12 deficiency and study 2 analyzed vit B12 deficiency incidence according to the presence/absence of DPN. Moreover, we compared the results with respect to metformin use. Results: In study 1, DPN incidence per 10000 person-year (PY) was 179.7 and 76.6 in the vit B12 and non-vit B12 deficiency groups, respectively. The adjusted HR was 1.32 (95% CI; 1.21–1.44, P < 0.05) and metformin use elicited a more significant effect of DPN occurrence in patient with vit B12 deficiency (HR: 5.76 (95% CI; 5.28–6.29). In study 2, vit B12 deficiency incidence per 10000 PY was 250.6 and 129.4 in the DPN and non-DPN groups, respectively. The adjusted HR was 2.44 (95% CI; 2.24–2.66, P < 0.05), however, metformin prescription was associated with the reduced incidence of vit B12 deficiency in DPN patients (HR 0.68 (95% CI; 0.62–0.74, P < 0.05). Conclusion: DPN occurrence increased in diabetes with vit B12 deficiency and the incidence of vit B12 deficiency was also high in DPN patients. However, metformin showed opposite effects in both cohorts. Further studies clarifying the causal relationship among DPN occurrence, vit B12 deficiency, and metformin use are warranted.