Association of vitamin B12 deficiency in people with type 2 diabetes on metformin and without metformin: a multicenter study, Karachi, Pakistan

Abstract

Objective: To assess the prevalence of vitamin B₁₂ deficiency in people with type 2 diabetes mellitus (T2DM) on metformin and without metformin.

Methodology: Between May 2018 and January 2019, this prospective multicenter observational study recruited participants from seven centers in four provinces of Pakistan (Sindh, Punjab, Baluchistan and Khyber Pakhtunkhwa). Participants with T2DM treated with metformin for >2 years and those not on metformin underwent assessment of hemoglobin, vitamin B₁₂, homocysteine and diabetic neuropathy (vibration perception threshold (VPT) >15V) and painful diabetic neuropathy (Douleur Neuropathique 4 (DN4) ≥4) and Diabetic Neuropathy Symptom (DNS) score ≥1.

Results: Of 932 subjects, 645 (69.2%) were treated with metformin, while 287 (30.8%) were not on metformin. Overall, B₁₂ deficiency (<200 pg/mL) was significantly higher in metformin users of 25 (3.9%), compared with non-metformin users of 6 (2.1%), while B₁₂ insufficiency (200-300 pg/mL) was significantly lower in metformin users of 117 (18.4%) compared with non-metformin users of 80 (27.9%). Subjects with B₁₂ deficiency and insufficiency with hyperhomocysteinemia (≥15) were found in 19 (76%) µmol/L and 69 (60.5%) µmol/L in metformin users compared with 6 (100%) µmol/L and 57 (73.1%) μmol/L in non-metformin users, respectively. VPT>25 and DN4 score ≥4 were significantly higher in B₁₂-deficient metformin users compared with non-metformin users. Similarly, DNS score ≥1 was non-significantly higher in B₁₂-deficient metformin users compared with non-metformin users.

Conclusion: This study shows that vitamin B₁₂ insufficiency was frequently found in our population and may progress into B₁₂ deficiency. It is also associated with neuropathy in subjects on metformin. Further interventional studies to assess the benefit of B₁₂ treatment on painful neuropathy in patients on metformin may be warranted. B₁₂ levels may be checked in people with T2DM using metformin for >2 years.

Keywords: blood glucose monitoring; clinical research; control; metformin.