Background:

Metformin-induced vitamin B₁₂ deficiency state or metformin-induced hypocobalaminemia is gradually becoming an epidemic among diabetic patients on moderate-to-high doses of metformin or those diabetic patients on metformin for a long period of time. The potential effect of chronic metformin pharmacotherapy to cause vitamin B₁₂ deficiency with abnormalities in haematologic indices and central/peripheral neuropathy has been widely reported. Long-term usage of metformin has been reported to be associated with intestinal malabsorption of vitamin B₁₂ culminating in vitamin B₁₂ deficiency with likely associated haematologic abnormalities (including macro-ovalocytic anaemia and immune dysfunctioning due to hypersegmentation of polymorphonuclear leukocytes), central/peripheral neuropathy and manifestation of biochemical derangements such as elevated homocysteine and methyl malonate levels.

Aim:

This study aimed to determine the correlation between serum vitamin B₁₂ levels and various haematologic indices among metformin-treated type 2 diabetic patients in a clinical practice setting with the rational purpose of alleviating/preventing the associated derangements.

Materials and Methods:

This was a case-control, prospective, analytical, observational study of 200 adult participants (100 per group) attending the Endocrinology Out-patients Clinic of Irrua Specialist Teaching Hospital, Irrua, Edo State, Nigeria. For each participant, serum vitamin B₁₂ level was determined using a vitamin B₁₂ immunoassay technique, while the corresponding complete blood count was done using PCE-210N autohaematology analyser. Data were presented using tables and figures. Chi-square test was used to compare categorical variables, Student t-test was used in comparing means of continuous variables, while Pearson’s correlation study was done to determine the existence of any statistically significant correlation(s) between the serum vitamin B₁₂ levels and various haematologic indices among the participants.

Results:

Approximately 41% versus 20% of the metformin-treated and metformin-naive diabetic patients, respectively, had frank vitamin B₁₂ deficiency. There was a statistical difference between the total serum vitamin B₁₂ levels in male and female diabetic patients with p = 0.048. Also, statistically significant differences existed with respect to mean corpuscular volume (MCV), mean corpuscular haemoglobin and total white blood cells count among the metformin-treated and metformin-naive diabetic patients. Furthermore, a statistically significant weak positive correlation existed between pack cell volume (PCV) and serum vitamin B₁₂ level (r = +0.148, p = 0.037), but a statistically significant weak negative correlation existed between MCV and serum vitamin B₁₂ level (r = −0.245, p = 0.0001). In addition, the test for associations between the serum vitamin B₁₂ categorization status or metformin exposure status and the peripheral neuropathy components assessment revealed that there were statistically significant associations between the serum vitamin B₁₂ categorization status or metformin exposure status versus pain sense (p < 0.0001 or <0.001), vibration sense (p < 0.0001 or <0.001) and light touch sense (p < 0.0001 or <0.001) among the participants.

Conclusion:

In this study, statistically significant weak positive and weak negative correlations existed between serum vitamin B₁₂ level versus PCV, and serum vitamin B₁₂ level versus MCV, respectively. The peripheral neuropathy components assessment revealed that there were statistically significant associations between the serum vitamin B₁₂ categorization status or metformin exposure status versus pain sense, vibration sense and light touch sense among the participants.

Search results

Evaluating the correlation between serum vitamin B 12 levels and various haematologic indices among metformin-treated type 2 diabetic patients: A prospective analytical study