Vol 11, No 1 (2022)
Letter to the Editor
Published online: 2021-12-29

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letter to the editor

ISSN 2450–7458
e-ISSN 2450–8187

Vitamin B12 and risk of diabetic foot ulcers: a new paradigm

Amir Yarahmadi12Daryoush Hamidi Alamdari13Negar Azarpira2Zohreh Mostafavi-Pour45
1Department of Clinical Biochemistry, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
2Transplant Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
3Surgical Oncology Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
4Department of Biochemistry, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran
5Autophagy Research Center, Shiraz University of Medical Sciences, Shiraz, Iran

Address for correspondence:

Professor Zohreh Mostafavi-Pour

Department of Biochemistry, School of Medicine

Shiraz University of Medical Sciences

Shiraz, Iran

Autophagy Research Center

Shiraz University of Medical Sciences

Shiraz, Iran

e-mail: zmostafavipour88@yahoo.co.uk

Clinical Diabetology 2022, 11; 1:52–53

DOI: 10.5603/DK.a2021.0054

Received: 16.06.2021 Accepted: 24.10.2021

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.


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