Kang Donghoon, Yun Jae-Seung, Ko Sun-Hye, Lim Tae-Seok, Ahn Yu-Bae, Park Yong-Moon, Ko Seung-Hyun
Division of Endocrinology and Metabolism, Department of Internal Medicine, St. Vincent's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea.
Department of Epidemiology and Biostatistics, Arnold School of Public Health, University of South Carolina, Columbia, South Carolina, United States of America.
PLoS One. 2014 Oct 9;9(10):e109878. doi: 10.1371/journal.pone.0109878. eCollection 2014.
Long-term and high-dose treatment with metformin is known to be associated with vitamin B12 deficiency in patients with type 2 diabetes. We investigated whether the prevalence of B12 deficiency was different in patients treated with different combination of hypoglycemic agents with metformin during the same time period. A total of 394 patients with type 2 diabetes treated with metformin and sulfonylurea (S+M group, n = 299) or metformin and insulin (I+M group, n = 95) were consecutively recruited. The vitamin B12 and folate levels were quantified using the chemiluminescent enzyme immunoassay. Vitamin B12 deficiency was defined as vitamin B12≤300 pg/mL without folate deficiency (folate>4 ng/mL). The mean age of and duration of diabetes in the subjects were 59.4±10.5 years and 12.2±6.7 years, respectively. The mean vitamin B12 level of the total population was 638.0±279.6 pg/mL. The mean serum B12 levels were significantly lower in the S+M group compared with the I+M group (600.0±266.5 vs. 757.7±287.6 pg/mL, P<0.001). The prevalence of vitamin B12 deficiency in the metformin-treated patients was significantly higher in the S+M group compared with the I+M group (17.4% vs. 4.2%, P = 0.001). After adjustment for various factors, such as age, sex, diabetic duration, duration or daily dose of metformin, diabetic complications, and presence of anemia, sulfonylurea use was a significant independent risk factor for B12 deficiency (OR = 4.74, 95% CI 1.41-15.99, P = 0.012). In conclusion, our study demonstrated that patients with type 2 diabetes who were treated with metformin combined with sulfonylurea require clinical attention for vitamin B12 deficiency and regular monitoring of their vitamin B12 levels.
已知长期大剂量使用二甲双胍治疗2型糖尿病患者会导致维生素B12缺乏。我们调查了在同一时期使用不同降糖药物与二甲双胍联合治疗的患者中，维生素B12缺乏的患病率是否存在差异。连续招募了394例接受二甲双胍和磺脲类药物治疗的2型糖尿病患者（S+M组，n = 299）或二甲双胍和胰岛素治疗的患者（I+M组，n = 95）。采用化学发光酶免疫分析法对维生素B12和叶酸水平进行定量检测。维生素B12缺乏定义为维生素B12≤300 pg/mL且无叶酸缺乏（叶酸>4 ng/mL）。受试者的平均年龄和糖尿病病程分别为59.4±10.5岁和12.2±6.7年。总人群的平均维生素B12水平为638.0±279.6 pg/mL。与I+M组相比，S+M组的平均血清B12水平显著降低（600.0±266.5 vs. 757.7±287.6 pg/mL，P<0.001）。与I+M组相比，S+M组接受二甲双胍治疗的患者中维生素B12缺乏的患病率显著更高（17.4% vs. 4.2%，P = 0.001）。在对年龄、性别、糖尿病病程、二甲双胍的使用时长或每日剂量、糖尿病并发症以及贫血情况等多种因素进行校正后，使用磺脲类药物是维生素B12缺乏的显著独立危险因素（OR = 4.74，95%CI 1.41 - 15.99，P = 0.012）。总之，我们的研究表明，接受二甲双胍联合磺脲类药物治疗的2型糖尿病患者需要临床关注维生素B12缺乏情况，并定期监测其维生素B12水平。
