Association of vitamin B12 deficiency and metformin use in patients with type 2 diabetes

J Korean Med Sci. 2014 Jul;29(7):965-72. doi: 10.3346/jkms.2014.29.7.965. Epub 2014 Jul 11.

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 ≤ 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 ≤ 1,000 mg, the adjusted odds ratio for 1,000-2,000 mg, and ≥ 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 ≥ 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 (≥ 4 yr) of treatment.

Keywords: Diabetes Mellitus; Metformin; Type 2; Vitamin B12 Deficiency.

MeSH terms

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

Substances

  • Hypoglycemic Agents
  • Metformin
  • Folic Acid
  • Vitamin B 12