Association between vitamin B12 level and clinical peripheral neuropathy in type 2 diabetic patients on metformin therapy

Abstract

Background Vitamin B12 malabsorption is one of the side effects of long-term metformin intake. Prolonged vitamin B12 deficiency can lead to irreversible nervous system damage. So, the current study aimed to determine the association between serum vitamin B12 level and clinical peripheral neuropathy among type 2 DM patients who are on metformin in comparison to those not taking it. It is a cross-sectional study that was conducted in Egypt and recruited 100 type 2 diabetic patients who were divided into 2 groups: metformin treated, and non-metformin treated (50 subjects per group). The collected data included personal history, medical history, dietetic history that included frequency of eating food rich in vitamin B12 and clinical peripheral neuropathy assessment by Toronto Clinical Scoring System (TCSS). Blood samples were collected for assessment of HbA1c and vitamin B12 level. Results Vitamin B12 deficiency was present in 4% of metformin group and 2% of non-metformin group. The mean value of vitamin B12 between metformin users (624.3 ± 364.1 pg/ml) and non-metformin users (991.0 ± 489.9 pg/ml) showed a high significant difference, p value < 0.001. There was a significant difference between study groups regarding HbA1c level (p value = 0.03). Peripheral neuropathy was significantly associated with HbA1c (p value = 0.04) and female gender (p value = 0.001). Conclusions Vitamin B12 level was lower in type 2 diabetic patients on metformin compared to those on other oral anti-diabetic drugs, but without significant deficiency. Peripheral neuropathy was significantly associated with poor glycemic control and female gender, but was not associated with vitamin B12 deficiency.

Prevalence and Characteristics of Vitamin B12 Deficiency Among Patients with Type-2 Diabetes Mellitus in Bahrain- A Cross-Sectional Study

“…Although VB12 is an important factor for neurological functioning, the association between low VB12 and neuropathy was not evident in our research. A study conducted in Egypt reported similar ndings 25 . This could be elucidated by the early detection and treatment of VB12 de ciency in the pre-clinical stage and the overall low prevalence of neuropathy among the cohort.…”

Effect of Metformin on Vitamin B12 Deficiency in Patients With Type 2 Diabetes Mellitus and Factors Associated With It: A Meta-Analysis

“…After removing duplicates, we reviewed the titles and abstracts of 1598 articles and identified 180 possible eligible studies for full-text screening. Among all the eligible studies, 17 were included in the current meta-analysis [11][12][13][14][15][16][17][18][19][20][21][22][23][24][25][26][27]. Among all the included studies, 13 were cross-sectional studies, 3 were retrospective cohorts, and 1 was a case-control study.…”

“…FIGURE 2: Forest plot showing the association of metformin with vitamin B12 deficiencySources: References[12,14,16,21,23,[25][26] …”

Peripheral Neuropathy: A review of mechanism-based treatments with a focus on metformin as a possible choice

“…Contrary to initial disappointing results, Russo et al mentioned that in type 2 DM patients who received Metformin for at least 6 months, vitamin B12 deficiency was just mild and didn't have a relationship with developing diabetic neuropathy [76]. Fakkar et al confirmed the previous study and mentioned that despite the lower levels of vit B12 in Metformin recipients, it is not associated with higher incidence of developing PN [77]. The last systematic review published in could not analyze the effect of Metformin on PN in diabetic patients due to the lack of data [78].…”