Effects of a change in the pattern of insulin delivery on carbohydrate tolerance in diabetic and nondiabetic humans in the presence of differing degrees of insulin resistance
Effects of a change in the pattern of insulin delivery on carbohydrate tolerance in diabetic and nondiabetic humans in the presence of differing degrees of insulin resistance
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DOI：
10.1172/jci118678
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发表时间：
1996-05-15
影响因子：
15.9
通讯作者：
Rizza, RA
中科院分区：
文献类型：
--
作者：
Basu, A;Alzaid, A;Rizza, RA
虽然已经确定非胰岛素依赖型糖尿病患者在胰岛素分泌和作用方面都有缺陷，但每种缺陷对葡萄糖耐受不良的相对影响尚不清楚。因此，在两种情况下研究了非糖尿病（瘦型和肥胖型）和非胰岛素依赖型糖尿病受试者。在每种情况下，用生长抑素抑制胰岛素分泌，并以模拟摄入50 g葡萄糖后正常观察到的全身递送速率的模式和量输注葡萄糖。还输注胰岛素，以模拟在不同的糖尿病和非糖尿病受试者组中观察到的餐后胰岛素曲线。使用同位素稀释法测量葡萄糖周转率。胰岛素输送的延迟模式（即，糖尿病胰岛素谱）导致所有组的葡萄糖浓度升高（P < 0.05）;然而，该效应是短暂的，仅导致综合血糖反应适度增加。胰岛素作用的单一缺陷对血糖峰值浓度几乎没有影响;然而，它延长了高血糖的持续时间，导致综合血糖反应增加2.5-4.2倍（P < 0.05）。胰岛素分泌和作用模式的联合缺陷是累加的而不是协同的。这两种缺陷通过改变内源性葡萄糖释放的抑制和刺激葡萄糖处置而引起高血糖症，而肥胖糖尿病和非糖尿病受试者在葡萄糖清除方面具有可比的缺陷，非胰岛素依赖型糖尿病受试者也具有肝脏胰岛素作用的缺陷。因此，胰岛素分泌和作用模式的异常单独或组合损害葡萄糖耐量。胰岛素作用的孤立缺陷比胰岛素分泌模式的孤立改变具有更显著和更持久的影响。肝和肝外胰岛素抵抗导致显著和持续的高血糖。(J. Clin. Invest. 1996. 97：2351-2361.）
While it is well established that people with non-insulin dependent diabetes mellitus have defects in both insulin secretion and action, the relative contribution of each to glucose intolerance is not known, Therefore, nondiabetic (lean and obese) and non-insulin dependent diabetes mellitus subjects were studied on two occasions. On each occasion, insulin secretion was inhibited with somatostatin and glucose was infused in a pattern and amount that mimicked the systemic delivery rate normally observed after ingestion of 50 g of glucose, Insulin also was infused so as to mimic postprandial insulin profiles observed in separate groups of diabetic and nondiabetic subjects after food ingestion. Glucose turnover was measured using the isotope dilution method. A delayed pattern of insulin delivery (i.e., a ''diabetic'' insulin profile) led to higher (P < 0.05) glucose concentrations in all groups; however, the effects were transient, resulting in only a modest increase in the integrated glycemic responses. An isolated defect in insulin action had little effect on peak glucose concentration; however, it prolonged the duration of hyperglycemia, leading to a 2.5-4.2-fold increase (P < 0.05) in the integrated glycemic response, A combined defect in the pattern of insulin secretion and action was additive rather than synergistic. Both defects caused hyperglycemia by altering suppression of endogenous glucose release and stimulation of glucose disposal, Whereas obese diabetic and nondiabetic subjects had comparable defects in glucose clearance, non-insulin dependent diabetes mellitus subjects also had defects in hepatic insulin action. Thus, abnormalities in the pattern of insulin secretion and action alone or in combination impair glucose tolerance. An isolated defect in insulin action has a more pronounced and prolonged effect than does an isolated change in the pattern of insulin secretion, Hepatic and extrahepatic insulin resistance results in marked and sustained hyperglycemia. (J. Clin. Invest. 1996. 97:2351-2361.)