Widén E I, Eriksson J G, Groop L C
Fourth Department of Medicine, Helsinki University Hospital, Finland.
Diabetes. 1992 Mar;41(3):354-8. doi: 10.2337/diab.41.3.354.
Many first-degree relatives of patients with non-insulin-dependent diabetes mellitus (NIDDM) are characterized by insulin resistance. Because metformin improves peripheral insulin sensitivity, we examined the acute effect of metformin and placebo on glucose and lipid metabolism in nine insulin-resistant first-degree relatives of NIDDM patients with the euglycemic insulin-clamp technique combined with indirect calorimetry and infusion of [3-3H]glucose. Either placebo or 500 mg metformin was taken in random order twice the day before and once 1 h before the clamp. Nine healthy individuals without family history of diabetes served as control subjects. Basal plasma glucose was normal and did not differ between the metformin and the placebo study (4.8 +/- 0.2 vs. 5.0 +/- 0.2 mM) and neither did basal hepatic glucose production (10.59 +/- 0.54 vs. 10.21 +/- 0.80 mumol.kg-1.min-1). Insulin-stimulated glucose disposal was significantly increased by 25% after metformin compared with placebo (26.67 +/- 2.87 vs. 21.31 +/- 1.73 mumol.kg-1.min-1, P less than 0.05). The enhancement in glucose utilization was primarily due to normalization of nonoxidative glucose disposal (from 8.02 +/- 1.35 to 15.07 +/- 2.69 mumol.kg-1.min-1, P less than 0.01, vs. 15.65 +/- 2.72 mumol.kg-1.min-1 in control subjects). In contrast, glucose oxidation during the clamp was slightly lower after metformin compared with both placebo (11.59 +/- 0.83 vs. 13.30 +/- 1.00 mumol.kg-1.min-1, P = 0.06) and healthy control subjects (15.68 +/- 1.38 mumol.kg-1.min-1, P less than 0.05). We conclude that acutely administered metformin improves peripheral insulin sensitivity in insulin-resistant normoglycemic individuals primarily by stimulating the nonoxidative pathway of glucose metabolism.
许多非胰岛素依赖型糖尿病（NIDDM）患者的一级亲属具有胰岛素抵抗的特征。由于二甲双胍可改善外周胰岛素敏感性，我们采用正常血糖胰岛素钳夹技术结合间接测热法及输注[3-³H]葡萄糖，研究了二甲双胍和安慰剂对9名NIDDM患者胰岛素抵抗的一级亲属的血糖和脂质代谢的急性影响。在钳夹前一天，安慰剂或500mg二甲双胍随机服用两次，钳夹前1小时服用一次。9名无糖尿病家族史的健康个体作为对照。基础血浆葡萄糖正常，二甲双胍组和安慰剂组之间无差异（4.8±0.2 vs. 5.0±0.2mM），基础肝葡萄糖生成也无差异（10.59±0.54 vs. 10.21±0.80μmol·kg⁻¹·min⁻¹）。与安慰剂相比，二甲双胍治疗后胰岛素刺激的葡萄糖处置显著增加25%（26.67±2.87 vs. 21.31±1.73μmol·kg⁻¹·min⁻¹，P<0.05）。葡萄糖利用的增强主要是由于非氧化葡萄糖处置正常化（从8.02±1.35至15.07±2.69μmol·kg⁻¹·min⁻¹，P<0.01，而健康对照为15.65±2.72μmol·kg⁻¹·min⁻¹）。相比之下，与安慰剂组（11.59±0.83 vs. 13.30±1.00μmol·kg⁻¹·min⁻¹，P = 0.06）和健康对照组（15.68±1.38μmol·kg⁻¹·min⁻¹，P<0.05）相比，二甲双胍治疗后钳夹期间的葡萄糖氧化略低。我们得出结论，急性给予二甲双胍主要通过刺激葡萄糖代谢的非氧化途径，改善胰岛素抵抗的正常血糖个体的外周胰岛素敏感性。
