Judzewitsch R G, Pfeifer M A, Best J D, Beard J C, Halter J B, Porte D
J Clin Endocrinol Metab. 1982 Aug;55(2):321-8. doi: 10.1210/jcem-55-2-321.
To determine the effect of chronic sulfonylurea therapy on islet function in noninsulin-dependent diabetes mellitus (NIDDM), studies were performed in 18 untreated NIDDM patients before and after 12-16 weeks of chlorpropamide therapy. Fasting plasma glucose (FPG) fell with chlorpropamide therapy from 249 +/- 16 to 157 +/- 8 mg/dl (mean +/- SEM; P less than 0.001), and basal insulin increased from 17 +/- 2 to 24 +/- 3 microU/ml (P less than 0.001). The percent change in basal insulin correlated with the pretreatment FPG (r = 0.62; P less than 0.01) and inversely with the change in FPG during chlorpropamide (r = -0.57; P less than 0.025). Thus, patients with the highest pretreatment FPG showed the largest relative increase in basal insulin and the largest fall of FPG with chlorpropamide therapy. In nine patients, arginine-stimulated acute insulin responses (AIR) were studied at each of three plasma glucose (PG) levels both before and during chlorpropamide treatment. AIR at FPG was not different before and during treatment. However, when PG during treatment was matched by glucose infusion to the pretreatment FPG, the AIR was clearly increased during chlorpropamide therapy (176 +/- 65 vs. 49 +/- 11 microU/ml; P less than 0.02). When AIR is plotted against PG for each individual, the slope of the regression line generated (slope of glucose potentiation) is a measure of that patient's islet sensitivity to glucose. The logarithm of the slope of glucose potentiation correlated inversely with FPG (r = -0.92; P less than 0.001). Chlorpropamide treatment increased the slopes of potentiation from 0.26 +/- 0.11 to 1.47 +/- 0.70 (P less than 0.01). We conclude that chronic chlorpropamide therapy augments both basal and stimulated insulin secretion in NIDDM and that this may be an important mechanism of the drug's hypoglycemic effect. The data support the hypothesis that the hyperglycemia of NIDDM is related to islet insensitivity to glucose and that chlorpropamide treatment improves this impairment.
为了确定慢性磺脲类药物治疗对非胰岛素依赖型糖尿病（NIDDM）患者胰岛功能的影响，我们对18例未经治疗的NIDDM患者在进行12 - 16周氯磺丙脲治疗前后进行了研究。氯磺丙脲治疗后，空腹血糖（FPG）从249±16降至157±8mg/dl（均值±标准误；P＜0.001），基础胰岛素水平从17±2升至24±3μU/ml（P＜0.001）。基础胰岛素的变化百分比与治疗前FPG相关（r = 0.62；P＜0.01），与氯磺丙脲治疗期间FPG的变化呈负相关（r = -0.57；P＜0.025）。因此，治疗前FPG最高的患者基础胰岛素相对增加最大，且氯磺丙脲治疗后FPG下降幅度最大。在9例患者中，在氯磺丙脲治疗前和治疗期间，分别在三个血浆葡萄糖（PG）水平下研究了精氨酸刺激的急性胰岛素反应（AIR）。治疗前和治疗期间空腹血糖时的AIR无差异。然而，当治疗期间的PG通过葡萄糖输注调整至治疗前FPG水平时，氯磺丙脲治疗期间的AIR明显增加（176±65对49±11μU/ml；P＜0.02）。当针对每个个体将AIR与PG作图时，所生成回归线的斜率（葡萄糖增强斜率）是该患者胰岛对葡萄糖敏感性的一种度量。葡萄糖增强斜率的对数与FPG呈负相关（r = -0.92；P＜0.001）。氯磺丙脲治疗使增强斜率从0.26±0.11增加至1.47±0.70（P＜0.01）。我们得出结论，慢性氯磺丙脲治疗可增强NIDDM患者的基础和刺激胰岛素分泌，这可能是该药物降糖作用的重要机制。这些数据支持以下假设，即NIDDM的高血糖与胰岛对葡萄糖不敏感有关，且氯磺丙脲治疗可改善这种损害。
