Ginsberg H, Kimmerling G, Olefsky J M, Reaven G M
J Clin Invest. 1975 Mar;55(3):454-61. doi: 10.1172/JCI107951.
We have used a continuous intravenous infusion of glucose (6 mg/kg/min), insulin (80 mU/min), epinephrine (6 mug/min), and propranolol (0.08 mg/min) to directly assess insulin resistance in 14 untreated adult onset diabetics with a mean (plus or minus SE) fasting plasma glucose level of 217 plus or minus 17 mg/100 ml. During the infusion endogenous insulin secretion is inhibited and steady-state plasma glucose and insulin levels are achieved after 90 min. Since similar steady-state levels of plasma insulin are achieved in all subjects, the plasma glucose concentration observed during the steady-state period is a measure of an individual's insulin resistance. Under these conditions, the mean (plus or minus SE) steady-state plasma glucose level of the 14 diabetic patients was 350 plus or minus 16 mg/100 ml, while that of 12 normal subjects was 121 plus or minus 4 mg/100 ml. Additional studies were performed in which control subjects and patients with diabetes had their fasting plasma glucose levels acutely raised or lowered to comparable levels before receiving the basic infusion mixture of glucose, insulin, epinephrine, and propranolol. The results of these studies indicated that differences in initial plasma glucose levels could not account for the different glucose responses of the two groups to the basic infusion. Finally, the mean (plus or minus SE) steady-state plasma glucose level of 104 plus or minus 17 mg/100 ml observed during the same basic infusion in five patients with fasting hyperglycemia (mean plus or minus SE, 142 plus or minus 12 mg/100 ml) secondary to chronic pancreatitis suggested that neither chronic hyperglycemia nor hypoinsulinemia per se necessarily lead to insulin resistance. These results demonstrate that marked insulin resistance exists in adult onset diabetics with fasting hyperglycemia. Since previous studies have documented the presence of insulin resistance in patients with chemical diabetes, the possibility exists that insulin resistance may be characteristic of adult onset diabetes mellitus.
我们采用持续静脉输注葡萄糖（6毫克/千克/分钟）、胰岛素（80毫国际单位/分钟）、肾上腺素（6微克/分钟）和普萘洛尔（0.08毫克/分钟）的方法，对14例未经治疗的成年起病型糖尿病患者直接评估胰岛素抵抗，这些患者的空腹血浆葡萄糖水平平均（±标准误）为217±17毫克/100毫升。在输注过程中，内源性胰岛素分泌受到抑制，90分钟后达到稳态血浆葡萄糖和胰岛素水平。由于所有受试者的血浆胰岛素稳态水平相似，因此在稳态期观察到的血浆葡萄糖浓度是个体胰岛素抵抗的一个指标。在这些条件下，14例糖尿病患者的平均（±标准误）稳态血浆葡萄糖水平为350±16毫克/100毫升，而12例正常受试者的为121±4毫克/100毫升。还进行了其他研究，其中在对照组受试者和糖尿病患者接受葡萄糖、胰岛素、肾上腺素和普萘洛尔的基础输注混合物之前，将他们的空腹血浆葡萄糖水平急性升高或降低到可比水平。这些研究结果表明，初始血浆葡萄糖水平的差异不能解释两组对基础输注的不同葡萄糖反应。最后，在5例继发于慢性胰腺炎的空腹血糖过高患者（平均±标准误，142±12毫克/100毫升）接受相同基础输注期间观察到的平均（±标准误）稳态血浆葡萄糖水平为104±17毫克/100毫升，这表明慢性高血糖症和低胰岛素血症本身不一定会导致胰岛素抵抗。这些结果表明，空腹血糖过高的成年起病型糖尿病患者存在明显的胰岛素抵抗。由于先前的研究已证明化学性糖尿病患者存在胰岛素抵抗，因此胰岛素抵抗可能是成年起病型糖尿病的特征。
