Best J D, Judzewitsch R G, Pfeifer M A, Beard J C, Halter J B, Porte D
Diabetes. 1982 Apr;31(4 Pt 1):333-8. doi: 10.2337/diab.31.4.333.
In 20 patients with untreated non-insulin-dependent diabetes mellitus (NIDDM), there was a positive relationship between fasting plasma glucose (FPG) and glucose production rate, calculated by the isotope dilution technique (r = 0.72, P less than 0.001). This suggests that glucose production rate is an important determinant of FPG in untreated NIDDM. Fifteen patients were also studied during therapy with chlorpropamide for 3-6 mo. During therapy, FPG was lower (133 +/- 9 vs. 216 +/- 20 mg/dl, mean +/- SEM; P less than 0.001), glucose production was lower (59.5 +/- 2.0 vs 77.6 +/- 4.9 mg/m2/min; P less than 0.005), and there was a significant correlation between the fall in glucose production and the fall in FPG (r = 0.59, P less than 0.05). Fasting IRI levels increased in some, but not all, patients during chlorpropamide (untreated 18 +/- 2, treated 21 +/- 2 muU/ml; P= NS). However, there was a significant relationship between the percent rise in IRI and the fall in glucose production during treatment (r = 0.75, P less than 0.001). Patients with a rise in fasting insulin during therapy had a greater fall in glucose production than those whose insulin did not rise (25.4 +/- 8.1 vs. 7.8 +/- 2.4 mg/m2/min; P less than 0.005). When a low-dose insulin infusion was given to approximate the increases of portal venous insulin during therapy, similar falls of glucose production occurred. We conclude that inhibition of endogenous glucose production during chronic chlorpropamide therapy is an important mechanism for the lowering of FPG and that enhanced insulin secretion is the reason for the major part of this inhibition. The small fall in glucose production in those patients whose insulin level did not rise during therapy suggests an additional contribution by some other mechanism.
在20例未经治疗的非胰岛素依赖型糖尿病（NIDDM）患者中，空腹血糖（FPG）与采用同位素稀释技术计算的葡萄糖生成率之间存在正相关关系（r = 0.72，P＜0.001）。这表明在未经治疗的NIDDM中，葡萄糖生成率是FPG的一个重要决定因素。还对15例患者进行了为期3至6个月的氯磺丙脲治疗研究。治疗期间，FPG降低（133±9 vs. 216±20 mg/dl，均值±标准误；P＜0.001），葡萄糖生成降低（59.5±2.0 vs 77.6±4.9 mg/m²/min；P＜0.005），并且葡萄糖生成的下降与FPG的下降之间存在显著相关性（r = 0.59，P＜0.05）。氯磺丙脲治疗期间，部分但并非所有患者的空腹IRI水平升高（未治疗时为18±2，治疗后为21±2 μU/ml；P=无显著差异）。然而，治疗期间IRI升高的百分比与葡萄糖生成的下降之间存在显著关系（r = 0.75，P＜0.001）。治疗期间空腹胰岛素升高的患者，其葡萄糖生成的下降幅度大于胰岛素未升高的患者（25.4±8.1 vs. 7.8±2.4 mg/m²/min；P＜0.005）。当给予低剂量胰岛素输注以模拟治疗期间门静脉胰岛素的增加时，葡萄糖生成出现类似程度的下降。我们得出结论，慢性氯磺丙脲治疗期间内源性葡萄糖生成的抑制是FPG降低的重要机制，胰岛素分泌增强是这种抑制的主要原因。治疗期间胰岛素水平未升高的患者，其葡萄糖生成的小幅下降提示存在其他机制的额外作用。
