Doeden B, Rizza R
J Clin Endocrinol Metab. 1987 May;64(5):902-8. doi: 10.1210/jcem-64-5-902.
To determine whether the severity of insulin resistance in obesity, as assessed by the traditional hyperinsulinemic glucose clamp, reflects the severity of resistance present during changing insulin concentrations, such as occur after meal ingestion, 9 moderately obese and 12 lean subjects were studied on 2 occasions: once during a primed continuous insulin infusion and once during a variable 8-step insulin infusion. Identical amounts of insulin were given on each occasion, and euglycemia was maintained by a glucose infusion. Stimulation of isotopically determined glucose utilization above the basal value was lower in the obese than in the lean subjects during the variable [2.4 +/- 0.5 (+/- SEM) vs. 5.4 +/- 0.7 g/m2; P = 0.004] and the constant (2.9 +/- 0.7 vs 4.2 +/- 0.9 g/m2; P = 0.32) insulin infusions; however, the differences were only significant with the variable insulin infusion. The variable insulin infusion also was associated with lower rates of activation of glucose utilization (slope, 0-90 min, 0.27 +/- 0.05 vs. 0.55 +/- 0.09 mg/m2 X min 2; P = 0.01) in obese compared to lean subjects. In contrast, rates of activation during the low constant infusion (0.24 +/- 0.05 vs. 0.29 +/- 0.06 mg/m2 X min 2; P = 0.51) did not differ in the lean and obese subjects. Despite identical amounts of insulin, stimulation of glucose utilization was greater (P less than 0.03) during the variable than during the constant insulin infusion in the lean subjects. In contrast, stimulation during the variable and constant insulin infusions was equal in the obese subjects. These observations indicate that insulin resistance in obesity is due to a defect in the rate as well as absolute response achieved and suggest that under conditions of daily living the contribution of insulin resistance to impaired carbohydrate tolerance is greater than that previously estimated by a constant insulin infusion.
为了确定通过传统的高胰岛素葡萄糖钳夹法评估的肥胖症中胰岛素抵抗的严重程度是否反映了在胰岛素浓度变化（如进食后出现的变化）期间存在的抵抗严重程度，对9名中度肥胖和12名瘦受试者进行了两次研究：一次是在给予负荷量后持续输注胰岛素期间，另一次是在进行可变的8步胰岛素输注期间。每次给予的胰岛素量相同，通过输注葡萄糖维持血糖正常。在可变胰岛素输注期间[2.4±0.5（±标准误）对5.4±0.7 g/m²；P = 0.004]和持续胰岛素输注期间（2.9±0.7对4.2±0.9 g/m²；P = 0.32），肥胖受试者中由同位素测定的葡萄糖利用率高于基础值的刺激低于瘦受试者；然而，差异仅在可变胰岛素输注时显著。与瘦受试者相比，可变胰岛素输注还与肥胖受试者中较低的葡萄糖利用率激活率相关（斜率，0 - 90分钟，0.27±0.05对0.55±0.09 mg/m²×分钟²；P = 0.01）。相比之下，在低剂量持续输注期间的激活率（0.24±0.05对0.29±0.06 mg/m²×分钟²；P = 0.51）在瘦和肥胖受试者中没有差异。尽管胰岛素量相同，但在瘦受试者中，可变胰岛素输注期间对葡萄糖利用率的刺激大于持续胰岛素输注期间（P < 0.03）。相比之下，肥胖受试者中可变和持续胰岛素输注期间的刺激相等。这些观察结果表明，肥胖症中的胰岛素抵抗是由于速率以及所达到的绝对反应存在缺陷，并表明在日常生活条件下，胰岛素抵抗对碳水化合物耐量受损的贡献大于先前通过持续胰岛素输注所估计的。
