About 40–50% of patients with diabetes experience peripheral neuropathy within ten years of disease onset [1]. Peripheral neuropathy associated with diabetes is one of the most important reasons for foot ulceration among these patients, finally leading to amputation [2, 3]. Diabetic foot ulcers (DFU) are one of the leading causes of mortality and morbidity worldwide [4].
Recent studies have shown that vitamin B12 deficiency plays an important role in developing peripheral neuropathy, especially in patients with a prolonged history of diabetes [2, 5]. Vitamin B12 plays a key functional role in the metabolism of fatty acids, which are crucial for maintaining the nerve myelin [6]. Furthermore, vitamin B12 is a cofactor in many intracellular enzymatic reactions necessary for correct central nervous system functions in healthy individuals [6]. Lengthy vitamin B12 insufficiency or deficiency can lead to neuronal degeneration and severe neurological damages, including peripheral neuropathy [7].
Patients with diabetes usually use antihyperglycemic drugs for regulating blood glucose levels. Metformin is the most widely prescribed antihyperglycemic agent for the treatment of type 2 diabetes [8]. Previous studies have reported that metformin induces vitamin B12 deficiency in patients with diabetes [8]. However, there are controversies in the metformin mechanism of action in the induction of vitamin B12 deficiency. The best-proposed mechanism is that metformin, through its biguanide hydrophobic tail binds to the hydrocarbon core of the cell membrane [9]. Then, metformin biguanide groups become positively charged and give their positive charge to the cell membrane. This positive charge can displace divalent cations like calcium and magnesium. It is well known that vitamin B12 uptake in the ileum is a calcium-dependent process; therefore, it can be impaired by metformin [9, 10].
Considering the high rates of patients with diabetes consuming metformin and the sequential vitamin B12 deficiency and following neuropathy, it is vital to monitor diabetic patients’ vitamin B12 levels to prevent costly and devastating DFU in the future.
Conflict of interest
None declared.