Metformin is very common
routine medication prescribed to nearly 120 million T2DM patients worldwide.
Close to one third of metformin-treated type-2
diabetes mellitus (T2DM) patients had vitamin B12 deficiency and the
deficiency was not associated with peripheral neuropathy.
Metformin is very common routine medication prescribed to nearly 120 million T2DM patients worldwide. Multiple studies have confirmed the correlation between long-term use of metformin and vitamin B12 deficiency. Irrespective of the evidences confirming the existence of a relationship between metformin use and vitamin B12 deficiency, the actual statistics of this association has not been quantified yet. The incidences of metformin-induced vitamin B12 deficiency ranges between 5.8% and 52%. Neuropathy might be the only clinical presentation of vitamin B12 deficiency, without haematological signs and symptoms. Vitamin B12 deficiency-associated peripheral neuropathy may interact with T2DM and thus, likely to be misdiagnosed as diabetic neuropathy. The long-term use of metformin, mediated by vitamin B12 deficiency, may contribute to increasing the substantial burden of peripheral neuropathy in T2DM patients. Several studies have tried to find the relationship between long-term metformin use and vitamin B12 deficiency-mediated peripheral neuropathy, but has come up with conflicting results.
Rationale behind research:
Objective:
The aim of this study was to investigate:
Study outcomes
Vitamin B12 deficiency:
NTSS-6 questionnaire was used to grade peripheral neuropathy. The investigator asked each participant about frequency and the intensity of six peripheral neuropathic symptoms, and used the answers to complete the questionnaire. The sum of scores for each patient were obtained (possible range between 0.00 and 21.96).
The relationship between vitamin B12 and peripheral neuropathy was investigated when two variables were in the binary and continuous forms.
Multiple logistic regression analysis was used to determine the risk factors for vitamin B12 deficiency.
Outcomes:
Figure 2. Correlation of Vitamin B12 and peripheral neuropathy.
The study demonstrated that the
prevalence of vitamin B12 deficiency, defined by levels <150
pmol/L, in metformin treated T2DM patients was as high as 28.1%. There was no
association between vitamin B12 and peripheral neuropathy. A novel
finding was the association between black South African descent and lower odds
of vitamin B12 deficiency in metformin-treated patients. Regular
screening for vitamin B12 deficiency in patients on long-term
metformin is recommended.
Vitamin B12 prevalence is found
to be higher in the present study as compared to previously reported estimates.
It is exactly the same as that of Beulens et al. study; however, mean metformin
dose and duration were higher in the present study. The study did not report
any statistically significant difference in neuropathy between those with
normal and deficient vitamin levels (36.8% vs. 32.3%, P=0.209). The present
study findings are also in concordance with the results of the cross-sectional
study of Chen et al. which revealed no significant differences between
metformin users and non-users when neuropathy status was assessed by both
objectives (monofilament and neurothesiometry) and relatively subjective
(questionnaires) measures. Low HbA1c level was a significant risk factor for
vitamin B12 deficiency in the final (OR=0.97, 95% CI: 0.95 to 0.99,
P=0.003) regression model. Kang et al. reported, but did not explain, the similar
results. They reported stronger association between HbA1c and vitamin B12
deficiency (OR=0.74, CI: 0.56 to 0.99). This study reveals the need for
setting-specific evidence to tackle the subject. Further research that
judiciously considers study design issues is warranted to clarify the possible
impact of metformin-induced vitamin B12 deficiency on peripheral
neuropathy in T2DM patients.
The
study established that the prevalence of vitamin B12 deficiency,
defined by levels <150 pmol/L, in metformin treated T2DM patients was as
high as 28.1% and there was no association between vitamin B12 and
peripheral neuropathy.
Ahmed et al. BMC Pharmacology and Toxicology (2016) 17:44
Vitamin B12 deficiency in metformin-treated type-2 diabetes patients, prevalence and association with peripheral neuropathy
Marwan A. Ahmed et al.
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