Kim Jiwoon, Ahn Chul Woo, Fang Sungsoon, Lee Hye Sun, Park Jong Suk
Department of Internal Medicine, Yongin Severance Hospital, Yonsei University College of Medicine, Yongin.
Department of Internal Medicine.
Medicine (Baltimore). 2019 Nov;98(46):e17918. doi: 10.1097/MD.0000000000017918.
Metformin can cause serum vitamin B12 deficiency, but studies on the influence of its duration and dose are lacking. We investigated vitamin B12 deficiency in patients with type 2 diabetes using metformin, in conjunction with other related factors.
This cross-sectional study included 1111 patients with type 2 diabetes who took metformin for at least 6 months. Serum vitamin B12 levels were quantified using a competitive-binding immunoenzymatic assay, and vitamin B12 deficiency was defined as serum B12 <300 pg/mL. Information on metformin use and confounding variables were collected from records or questionnaires and interviews.
Serum vitamin B12 deficiency occurred in 22.2% of patients (n = 247). After adjusting for confounders, a 1 mg increase in daily metformin dose was associated with a 0.142 pg/mL decrease in vitamin B12 (P < .001). Compared with a daily dose of <1000 mg, the adjusted odds ratios for 1000 to 1500, 1500 to 2000, and ≥2000 mg metformin were 1.72 (P = .080), 3.34 (P < .001), and 8.67 (P < .001), respectively. Vitamin B12 deficiency occurred less often in patients taking multivitamins (odds ratio 0.23; P < .001). After adjusting for confounding factors, there was no correlation between B12 deficiency and duration of metformin use. Serum homocysteine levels showed significant negative correlation with vitamin B12.
Metformin at ≥1500 mg/d could be a major factor related to vitamin B12 deficiency, whereas concurrent supplementation of multivitamins may potentially protect against the deficiency. Serum homocysteine levels were negatively correlated with vitamin B12 levels, suggesting that B12 deficiency due to metformin use may occur at the tissue level. However, this hypothesis will require further study.
二甲双胍可导致血清维生素B12缺乏，但关于其使用时长和剂量影响的研究尚缺。我们研究了使用二甲双胍的2型糖尿病患者的维生素B12缺乏情况以及其他相关因素。
这项横断面研究纳入了1111例服用二甲双胍至少6个月的2型糖尿病患者。采用竞争性结合免疫酶测定法定量血清维生素B12水平，维生素B12缺乏定义为血清B12<300 pg/mL。从记录或问卷及访谈中收集二甲双胍使用情况和混杂变量的信息。
22.2%的患者（n = 247）出现血清维生素B12缺乏。校正混杂因素后，二甲双胍每日剂量每增加1 mg，维生素B12水平降低0.142 pg/mL（P <.001）。与每日剂量<1000 mg相比，二甲双胍剂量为1000至1500、1500至2000以及≥2000 mg时的校正比值比分别为1.72（P = 0.080）、3.34（P <.001）和8.67（P <.001）。服用多种维生素的患者维生素B12缺乏的发生率较低（比值比0.23；P <.001）。校正混杂因素后，B12缺乏与二甲双胍使用时长之间无相关性。血清同型半胱氨酸水平与维生素B12呈显著负相关。
≥1500 mg/d的二甲双胍可能是导致维生素B12缺乏的主要因素，而同时补充多种维生素可能预防这种缺乏。血清同型半胱氨酸水平与维生素B12水平呈负相关，提示二甲双胍所致的B12缺乏可能发生在组织水平。然而，这一假设还需要进一步研究。
