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Observational Study
. 2016 Oct 7;17(1):44.
doi: 10.1186/s40360-016-0088-3.

Vitamin B12 deficiency in metformin-treated type-2 diabetes patients, prevalence and association with peripheral neuropathy

Marwan A Ahmed  1 , George Muntingh  2 , Paul Rheeder  3
Affiliations
Observational Study

Vitamin B12 deficiency in metformin-treated type-2 diabetes patients, prevalence and association with peripheral neuropathy

Marwan A Ahmed et al. BMC Pharmacol Toxicol. .

Abstract

Background: 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. The potential of the deficiency to cause or worsen peripheral neuropathy in type-2 diabetes mellitus (T2DM) patients has been investigated with conflicting results. The aim of the study was to investigate: 1) the prevalence of vitamin B12 deficiency in T2DM patients on metformin; 2) the association between vitamin B12 and peripheral neuropathy; 3) and the risk factors for vitamin B12 deficiency in these patients.

Methods: In this cross-sectional study, consecutive metformin-treated T2DM patients attending diabetes clinics of two public hospitals in South Africa were approached for participation. Participation included measuring vitamin B12 levels and assessing peripheral neuropathy using Neuropathy Total Symptom Score-6 (NTSS-6) questionnaire. The prevalence of vitamin B12 deficiency (defined by concentrations <150 pmol/L) was determined. Those with NTSS-6 scores >6 were considered to have peripheral neuropathy. The relationship between vitamin B12 and peripheral neuropathy was investigated when the two variables were in the binary and continuous forms. Multiple logistic regression was used to determine risk factors for vitamin B12 deficiency.

Results: Among 121 participants, the prevalence of vitamin B12 deficiency was 28.1 %. There was no difference in presence of neuropathy between those with normal and deficient vitamin levels (36.8 % vs. 32.3 %, P = 0.209). Vitamin B12 levels and NTSS-6 scores were not correlated (Spearman's rho =0.056, P = 0.54). HbA1c (mmol/mol) (OR = 0.97, 95 % CI: 0.95 to 0.99, P = 0.003) and black race (OR = 0.34, 95 % CI: 0.13 to 0.92, P = 0.033) were risk factors significantly associated with vitamin B12 deficiency. Metformin daily dose (gram) showed borderline significance (OR = 1.96, 95 % CI: 0.99 to 3.88, P = 0.053).

Conclusions: Close to third of metformin-treated T2DM patients had vitamin B12 deficiency. The deficiency was not associated with peripheral neuropathy. Black race was a protective factor for vitamin B12 deficiency.

Keywords: Diabetes; Metformin; Peripheral Neuropathy; Vitamin B12.

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Figures

Fig. 1
Fig. 1
Scatter plot for vitamin B12 levels vs. NTSS-6 scores among all metformin-treated T2DM patients
Fig. 2
Fig. 2
Scatter plot for vitamin B12 levels vs. NTSS-6 scores among metformin-treated T2DM patients with vitamin B12 deficiency
Fig. 3
Fig. 3
Scatter plot for vitamin B12 levels vs. NTSS-6 scores among metformin-treated T2DM patients with normal vitamin B12 levels
See this image and copyright information in PMC

References

    1. Viollet B, Guigas B, Sanz Garcia N, Leclerc J, Foretz M, Andreelli F. Cellular and molecular mechanisms of metformin: an overview. Clin Sci (Lond) 2012;122(6):253–270. doi: 10.1042/CS20110386. - DOI - PMC - PubMed
    1. Tomkin GH, Hadden DR, Weaver JA, Montgomery DA. Vitamin-B12 status of patients on long-term metformin therapy. Br Med J. 1971;2(5763):685–687. doi: 10.1136/bmj.2.5763.685. - DOI - PMC - PubMed
    1. de Jager J, Kooy A, Lehert P, Wulffele MG, van der Kolk J, Bets D, et al. Long term treatment with metformin in patients with type 2 diabetes and risk of vitamin B-12 deficiency: randomised placebo controlled trial. BMJ. 2010;340:c2181. doi: 10.1136/bmj.c2181. - DOI - PMC - PubMed
    1. Reinstatler L, Qi YP, Williamson RS, Garn JV, Oakley GP., Jr Association of biochemical B12 deficiency with metformin therapy and vitamin B12 supplements: the National Health and Nutrition Examination Survey, 1999–2006. Diabetes Care. 2012;35(2):327–333. doi: 10.2337/dc11-1582. - DOI - PMC - PubMed
    1. Hermann LS, Nilsson B, Wettre S. Vitamin B12 status of patients treated with metformin: a cross-sectional cohort study. Br J Diabetes Vasc Dis. 2004;4:401–404. doi: 10.1177/14746514040040060701. - DOI

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