Department of Metabolic Medicine, Osaka University Graduate School of Medicine, Osaka, Japan.
Endocr J. 2012;59(9):845-7. doi: 10.1507/endocrj.ej12-0068. Epub 2012 May 23.
We investigated the effect of metformin on hepatic glucose production and peripheral glucose uptake in Asian patients with type 2 diabetes mellitus. We recruited ten Japanese patients whose fasting glucose levels remained poorly controlled under meal-time injection of short-acting insulin. Metformin was added to their insulin therapy, and both hepatic glucose production and peripheral glucose uptake were assessed before and one week after metformin treatment, with the use of stable isotope [6,6-²H₂] glucose. Metformin was titrated to a maximum dose of 500 mg. As a result, fasting glucose levels and hepatic glucose production were significantly improved after the metformin treatment (p < 0.01 and 0.02), whereas their peripheral glucose uptake was not significantly changed (p = 0.63). Furthermore, the change of fasting glucose levels was significantly correlated with that of hepatic glucose production, whose coefficient ρ was 0.76 (p = 0.01). On the other hand, there was no significant correlation between the change of fasting glucose levels and that of peripheral glucose uptake (p = 0.43). In conclusion, low dose of metformin significantly reduced hepatic glucose production in Japanese patients with type 2 diabetes mellitus. The efficacy of metformin on correcting fasting hyperglycemia was strongly associated with reduced hepatic glucose production, rather than ameliorated peripheral glucose uptake.
我们研究了二甲双胍对亚洲 2 型糖尿病患者肝葡萄糖生成和外周葡萄糖摄取的影响。我们招募了 10 名日本患者，他们在接受餐时注射短效胰岛素后空腹血糖控制仍不理想。在开始使用二甲双胍治疗前和治疗 1 周后，我们使用稳定同位素 [6,6-²H₂] 葡萄糖评估了他们的肝葡萄糖生成和外周葡萄糖摄取情况。二甲双胍的剂量逐渐增加至最大 500mg。结果，二甲双胍治疗后空腹血糖水平和肝葡萄糖生成显著改善（p < 0.01 和 0.02），而外周葡萄糖摄取没有明显变化（p = 0.63）。此外，空腹血糖水平的变化与肝葡萄糖生成的变化显著相关，其相关系数 ρ 为 0.76（p = 0.01）。另一方面，空腹血糖水平的变化与外周葡萄糖摄取的变化之间没有显著相关性（p = 0.43）。总之，小剂量的二甲双胍可显著降低日本 2 型糖尿病患者的肝葡萄糖生成。二甲双胍纠正空腹高血糖的疗效与肝葡萄糖生成的降低密切相关，而与外周葡萄糖摄取的改善无关。
