J Korean Med Sci.  2014 Jul;29(7):965-972. 10.3346/jkms.2014.29.7.965.

Association of Vitamin B12 Deficiency and Metformin Use in Patients with Type 2 Diabetes

• Ko SH
• Ko SH
• Ahn YB
• Song KH
• Han KD
• Park YM
• Ko SH
• Kim HS

• KMID: 1789956
• DOI: http://doi.org/10.3346/jkms.2014.29.7.965

Abstract

We evaluated the prevalence of vitamin B12 deficiency and associated factors in type 2 diabetes patients using metformin. A total of 799 type 2 diabetes patients using metformin was enrolled. Vitamin B12 and folate levels were quantified by chemiluminescent enzyme immunoassay. Vitamin B12 deficiency was defined as vitamin B12 < or = 300 pg/mL without folate deficiency (folate > 4 ng/mL). The prevalence of vitamin B12 deficiency in metformin-treated type 2 diabetes patients was 9.5% (n = 76), and the mean vitamin B12 level was 662.5 +/- 246.7 pg/mL. Vitamin B12 deficient patients had longer duration of metformin use (P < 0.001) and higher daily metformin dose (P < 0.001) than non-deficient patients. Compared with daily metformin dose of < or = 1,000 mg, the adjusted odds ratio for 1,000-2,000 mg, and > or = 2,000 mg were 2.52 (95% CI, 1.27-4.99, P = 0.008) and 3.80 (95% CI, 1.82-7.92, P < 0.001). Compared with metformin use of < 4 yr, the adjusted odds ratios for 4-10 yr, and > or = 10 yr were 4.65 (95% CI, 2.36-9.16, P < 0.001) and 9.21 (95% CI, 3.38-25.11, P < 0.001), respectively. In conclusion, our study indicates that patients with type 2 diabetes treated with metformin should be screened for vitamin B12 deficiency, especially at higher dosages (> 1,000 mg) and longer durations (> or = 4 yr) of treatment.

Keyword

Diabetes Mellitus; Type 2; Metformin; Vitamin B12 Deficiency

MeSH Terms

Aged
Area Under Curve
Diabetes Mellitus, Type 2/complications/diagnosis/*drug therapy
Female
Folic Acid/blood
Humans
Hypoglycemic Agents/adverse effects/*therapeutic use
Immunoassay
Male
Metformin/adverse effects/*therapeutic use
Middle Aged
Odds Ratio
Patients
Prevalence
ROC Curve
Time Factors
Vitamin B 12/blood
Vitamin B 12 Deficiency/diagnosis/epidemiology/*etiology
Folic Acid
Hypoglycemic Agents
Metformin
Vitamin B 12

Figure

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  Fig. 1 Study design summarizing sample recruitment.

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  Fig. 2 Box-and-whisker plot for vitamin B12 level according to different duration of metformin use (A) and dose of metformin (B) (P for trend < 0.001 ).

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  Fig. 3 Receiver operator characteristic curve analysis for the duration of metformin use and daily metformin dose related to vitamin B12 deficiency.

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  Fig. 4 The prevalence of vitamin B12 deficiency stratified according to the daily doses and duration of metformin use (P < 0.001). m, month.

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