Ohara S, Komatsu R, Matsuyama T
Division of Atherosclerosis and Metabolism, Department of Internal Medicine, National Cardiovascular Center Hospital, Osaka, Japan.
Diabetes Res Clin Pract. 2004 Nov;66(2):133-8. doi: 10.1016/j.diabres.2004.03.007.
AIMS/HYPOTHESIS: The UK Prospective Diabetes Study (UKPDS) showed that biguanide therapy in overweight patients reduced the risk for any diabetes-related endpoint and all-cause mortality. Biguanides lower the blood glucose values without stimulation of insulin release. We have investigated the short-term effect of buformin on insulin sensitivity, solved tumor necrosis factor receptors (sTNFRs), and serum lipids in overweight subjects with type 2 diabetes mellitus (DM).
Thirteen overweight subjects with type 2 DM were examined. The subjects who were fed 20 kcal/kg body weight were divided into two subgroups according to whether they were treated by buformin (Buformin group), or dietary therapy alone (Diet group). Six patients were in Buformin group and seven patients were in Diet group. We calculated insulin-mediated glucose uptake by the liver and peripheral tissues using euglycemic hyperinsulinemic clamp combined with an oral glucose load before and after buformin treatment or diet therapy for 2 weeks.
Fasting plasma glucose, total cholesterol (T-chol), LDL-cholesterol (LDL-chol), and sTNFR2 were significantly decreased, and hepatic glucose uptake significantly increased from 32 +/- 7 to 42 +/- 7% (P < 0.05) in Buformin group but did not changed significantly in Diet group. However, the glucose infusion rate thought to express insulin sensitivity in peripheral tissue, TNF-alpha, sTNFR1, fasting plasma insulin, C-peptide, and NEFA levels did not change significantly in both the groups after treatment.
CONCLUSION/INTERPRETATION: Buformin improved insulin sensitivity in the liver and decreased T-chol, LDL-chol, and sTNFR2. The mechanism of action for buformin likely involves inhibition of TNF-alpha. Buformin lowers insulin resistance and risk factors for cardiovascular disease including serum lipid and will therefore, be useful in management of overweight type 2 DM patients.
目的/假设：英国前瞻性糖尿病研究（UKPDS）表明，超重患者接受双胍类药物治疗可降低任何糖尿病相关终点事件及全因死亡率的风险。双胍类药物可降低血糖值，且不刺激胰岛素释放。我们研究了二甲双胍对2型糖尿病（DM）超重患者胰岛素敏感性、可溶性肿瘤坏死因子受体（sTNFRs）和血脂的短期影响。
对13名超重的2型糖尿病患者进行检查。按照20千卡/千克体重给予受试者饮食，根据是否接受二甲双胍治疗（二甲双胍组）或仅接受饮食治疗（饮食组）将其分为两个亚组。二甲双胍组有6名患者，饮食组有7名患者。在二甲双胍治疗或饮食治疗2周前后，我们采用正常血糖高胰岛素钳夹技术结合口服葡萄糖负荷来计算肝脏和外周组织的胰岛素介导的葡萄糖摄取量。
二甲双胍组空腹血糖、总胆固醇（T-chol）、低密度脂蛋白胆固醇（LDL-chol）和sTNFR2显著降低，肝脏葡萄糖摄取量从32±7%显著增加至42±7%（P<0.05），而饮食组无显著变化。然而，治疗后两组中被认为可表达外周组织胰岛素敏感性的葡萄糖输注率、肿瘤坏死因子-α（TNF-α）、sTNFR1、空腹血浆胰岛素、C肽和游离脂肪酸（NEFA）水平均无显著变化。
结论/解读：二甲双胍改善了肝脏的胰岛素敏感性，降低了T-chol、LDL-chol和sTNFR2。二甲双胍的作用机制可能涉及对TNF-α的抑制。二甲双胍降低胰岛素抵抗以及包括血脂在内的心血管疾病危险因素，因此，对超重的2型糖尿病患者的管理有益。
