Context: The association between long-term metformin use and low vitamin B12 levels has been proven. However, the prevalence estimates of metformin-induced vitamin B12 deficiency showed considerable variation among the studies and have not been studied in African settings. The potential of the deficiency to cause or worsen peripheral neuropathy in T2DM patients has been investigated with conflicting results.
Objectives: The main objectives were to determine the prevalence of vitamin B12 deficiency among metformin users and to examine the association between the vitamin status and neuropathy in those patients. The secondary objective was to investigate the risk factors for vitamin B12 deficiency.
Research design and methods: In this cross-sectional study, consecutive T2DM patients on long-term metformin attending the diabetes clinic of the Department of Internal Medicine at Steve Biko Academic Hospital and Kalafong Hospital were approached for participation. Serum vitamin B12 levels were measured and neuropathy was assessed using the Neuropathy Total Symptom Score-6 (NTSS-6) questionnaire. Records were used to obtain other data. Vitamin B12 deficiency was defined by levels <150 pmol/L. Those with NTSS-6 scores >6 were considered to have neuropathy. The percentage of vitamin B12-deficient patients was determined. The relationship between vitamin B12 and neuropathy was investigated by using Chi-square test and Spearman?s correlation coefficient when the two variables are in the binary and continuous forms, respectively. Multiple logistic regression was used to determine the risk factors for vitamin B12 deficiency.
Results: Among 121 patients, the prevalence of vitamin B12 deficiency was 28.1%. There was no difference in presence of neuropathy between those with normal and deficient vitamin B12 levels (36.8% vs. 32.4%, P = 0.209). The levels of vitamin B12 and the NTSS-6 scores were not correlated (Spearman?s correlation coefficient = 0.056, P = 0.54). The multivariable logistic regression analysis showed that metformin dose (mg) (OR = 1.01, P = 0.050), HbA1c (OR = 0.71, P = 0.003) and black South African race (OR = 0.34, P = 0.033) were the only risk factors significantly associated with vitamin B12 deficiency.
Conclusions: Close to third of metformin-treated T2DM patients had vitamin B12 deficiency. The deficiency was, however, not associated with peripheral neuropathy. Black South African race was a protective factor for vitamin B12 deficiency.