Relationship between metformin use, vitamin B12 deficiency, hyperhomocysteinemia and vascular complications in patients with type 2 diabetes

[摘要] References(25)Cited-By(10)Aim of the study was to clarify the relationship between metformin-induced vitamin B12 (B12) deficiency, hyperhomocysteinemia and vascular complications in patients with type 2 diabetes.Serum B12 concentrations, homocysteine plasma levels, the presence of retinopathy and history of macroangiopathy (stroke or coronary heart disease) were analyzed in patients without renal dysfunction (serum creatinine<115 μmol/L).Firstly, B12 status was analyzed in 62 consecutive metformin-treated patients.Secondly, the relationship between B12, homocysteine and vascular complications was analyzed in 46 metformin-treated and 38 age- and sex-matched non-metformin-treated patients.Among the 62 consecutive metformin-treated patients, B12 was deficient (<150 pmol/L) in 8 (13%) and borderline-deficient (150-220 pmol/L) in 18 (29%): the larger the metformin dosage, the lower the B12 (P=0.02, Spearman’s ρ=-0.30).There were independent correlations between metformin use and B12 lowering (P=0.02, r = -0.25), and B12 lowering and elevation of homocysteine (Pr=-0.34).Elevation of homocysteine was a risk for retinopathy (P=0.02, OR 1.26, 95%CI 1.04-1.52).There was no significant relation between homocysteine and macroangiopathy.Correlation between B12 and homocysteine was stronger in metformin-treated (Pr=-0.48) than non-metformin-treated (P=0.04, r=-0.38) patients.In ten B12 deficient patients, B12 supplementation (1,500 μg/day) for 2.2±1.0 months with continued use of metformin raised B12 levels: 152±42 and 299±97 pmol/L before and after treatment, respectively (P<0.01).Metformin-induced B12 lowering in diabetes was associated with elevation of homocysteine, and hyperhomocysteinemia was independently related to retinopathy.Metformin-induced B12 deficiency was correctable with B12 supplementation.

[学科分类] 内分泌与代谢学

[关键词] Metformin;Homocysteine;Diabetes;Retinopathy