Roy Rudra Prasad, Ghosh Kaushik, Ghosh Manas, Acharyya Amitava, Bhattacharya Ambarish, Pal Mrinal, Chakraborty Sisir, Sengupta Nilanjan
Department of Medicine, Vivekananda Hospital, Durgapur, West Bengal, India.
Department of Medicine, Murshidabad Medical College, Berhampore, West Bengal, India.
Indian J Endocrinol Metab. 2016 Sep-Oct;20(5):631-637. doi: 10.4103/2230-8210.190542.
Long-term therapy with metformin was shown to decrease the Vitamin B level and manifested as peripheral neuropathy.
The aim of this study is to define the prevalence of Vitamin B deficiency in early Type 2 diabetic patients (duration ≤5 years or drug treatment ≤3 years) and the relationship among metformin exposure and levels of cobalamin (Cbl), folic acid, and homocysteine (Hcy) with severity of peripheral neuropathy.
This is a cross-sectional study involving randomly selected ninety patients (male 56, female 34) between age groups of 35 and 70 years, comparing those who had received >6 months of metformin (Group A) ( = 35) with those without metformin (Group B) ( = 35) and patients taking metformin with other oral hypoglycemic agent (Group C) ( = 20). Comparisons were made clinically, biochemically (serum Cbl, fasting Hcy, and folic acid), and with electrophysiological measures (nerve conduction studies of all four limbs). Comorbidities contributing to neuropathy were excluded from the study.
Group A patients (54.28%) were prone to develop peripheral neuropathy comparing Group B (28.57%) and Group C (35%). There was significantly low plasma level of Cbl in Group A (mean 306.314 pg/ml) than in Group B (mean 627.543 pg/ml) and Group C (mean 419.920 pg/ml). There was insignificant low-level plasma folic acid in Group A (16.47 ng/ml) than in Group B (16.81 ng/ml) and Group C (22.50 ng/ml). There was significantly high level of Hcy in Group A (mean 17.35 µmol/L) and Group C (mean 16.99 µmol/L) than in Group B (mean 13.22 µmol/L). Metformin users even for 2 years showed evidence of neuropathy on nerve conduction velocity though their body mass index and postprandial blood sugar were maintained. There was significant difference in between groups regarding plasma Cbl, folic acid, and Hcy level as significance level <0.05 in all three groups ( [2, 87] = 28.1, = 0.000), ( [2, 87] = 7.43, = 0.001), ( [2, 87] = 9.76, = 0.000). study shows significant ( < 0.05) lowering of Cbl and Hcy level in Group A (mean = 306.314, standard deviation [SD] = 176.7) than in Group C (mean = 419.92, SD = 208.23) and Group B (mean = 627.543, SD = 168.33).
Even short-term treatment with metformin causes a decrease in serum Cbl folic acid and increase in Hcy, which leads to peripheral neuropathy in Type 2 diabetes patients. A multicenter study with heterogeneous population would have increased the power of the study. We suggest prophylactic Vitamin B and folic acid supplementation or periodical assay in metformin user.
长期使用二甲双胍治疗会导致维生素B水平降低，并表现为周围神经病变。
本研究旨在确定2型糖尿病早期患者（病程≤5年或药物治疗≤3年）维生素B缺乏的患病率，以及二甲双胍暴露与钴胺素（Cbl）、叶酸和同型半胱氨酸（Hcy）水平与周围神经病变严重程度之间的关系。
这是一项横断面研究，随机选取90名年龄在35至70岁之间的患者（男性56名，女性34名），将接受二甲双胍治疗超过6个月的患者（A组）（n = 35）与未使用二甲双胍的患者（B组）（n = 35）以及同时服用二甲双胍和其他口服降糖药的患者（C组）（n = 20）进行比较。进行了临床、生化（血清Cbl、空腹Hcy和叶酸）以及电生理测量（四肢神经传导研究）。研究排除了导致神经病变的合并症。
与B组（28.5%）和C组（35%）相比，A组患者（54.28%）更容易发生周围神经病变。A组血浆Cbl水平（平均306.314 pg/ml）显著低于B组（平均627.543 pg/ml）和C组（平均419.920 pg/ml）。A组血浆叶酸水平（16.47 ng/ml）略低于B组（16.81 ng/ml）和C组（22.50 ng/ml），但差异不显著。A组（平均17.35 μmol/L）和C组（平均16.99 μmol/L）的Hcy水平显著高于B组（平均13.22 μmol/L）。即使使用二甲双胍仅2年的患者，尽管其体重指数和餐后血糖得到控制，但神经传导速度仍显示有神经病变的迹象。三组之间血浆Cbl、叶酸和Hcy水平存在显著差异，所有三组的显著性水平均<0.05（F[2, 87] = 28.1，P = 0.000），（F[2, 87] = 7.43，P = 0.001），（F[2, 87] = 9.76，P = 0.000）。研究表明，A组（平均 = 306.314，标准差[SD] = 176.7）的Cbl和Hcy水平显著低于C组（平均 = 419.92，SD = 208.23）和B组（平均 = 627.543，SD = 168.33）（P < 0.05）。
即使短期使用二甲双胍也会导致血清Cbl和叶酸水平降低以及Hcy水平升高，这会导致2型糖尿病患者出现周围神经病变。一项针对异质人群的多中心研究可能会增强本研究的效力。我们建议对使用二甲双胍的患者进行预防性维生素B和叶酸补充或定期检测。
