Turner R C, Holman R R, Matthews D, Hockaday T D, Peto J
Metabolism. 1979 Nov;28(11):1086-96. doi: 10.1016/0026-0495(79)90146-x.
The liver and beta cells function in a negative feedback loop, which appears to have a predominant role in regulating both the basal plasma glucose and insulin concentrations. The degree of basal hyperglycemia in diabetes probably provides a bioassay of both the effect of a reduction in insulin secretory capacity and the degree of insulin resistance. A mathematic model of the interaction of insulin deficiency and insulin resistance has been constructed, based on the known response characteristics of the beta cells to glucose, and of plasma glucose and insulin control of hepatic and peripherpal glucose flux. The degree to which beta cell deficiency increases basal plasma glucose reflects the hyperbolic shape of the normal insulin secretory response to different glucose concentrations. The height of basal plasma insulin is a function of the degree of insulin resistance. From the basal plasma insulin and glucose concentrations, the model provides an estimate of the degree to which both beta cell deficiency and insulin resistance contribute to diabetes. The predictions arising from the model are in accord with experimental data in man and in animals. In normal-weight diabetics who do not have increased insulin resistance, the model predicts that more than 85% of beta cell function has to be lost for the basal plasma glucose to rise to 6 mmol/liter, but a further 5%--10% loss increases the basal plasma glucose to over 10 mmol/liter. In a third of a consecutive series of 65 newly presenting, uncomplicated diabetics, both normal weight and obese, the analysis from the model suggested that insulin resistance, rather than beta cell deficit, was the predominant feature.
肝脏和β细胞在负反馈回路中发挥作用，这一回路似乎在调节基础血浆葡萄糖浓度和胰岛素浓度方面起主要作用。糖尿病患者基础高血糖的程度可能为胰岛素分泌能力降低的影响以及胰岛素抵抗程度提供了一种生物测定方法。基于β细胞对葡萄糖的已知反应特性以及血浆葡萄糖和胰岛素对肝脏和外周葡萄糖通量的控制，构建了一个胰岛素缺乏与胰岛素抵抗相互作用的数学模型。β细胞缺乏导致基础血浆葡萄糖升高的程度反映了正常胰岛素对不同葡萄糖浓度分泌反应的双曲线形状。基础血浆胰岛素水平是胰岛素抵抗程度的函数。根据基础血浆胰岛素和葡萄糖浓度，该模型可估计β细胞缺乏和胰岛素抵抗对糖尿病的影响程度。该模型得出的预测结果与人和动物的实验数据一致。在没有胰岛素抵抗增加的正常体重糖尿病患者中，该模型预测，基础血浆葡萄糖升至6毫摩尔/升时，超过85%的β细胞功能必须丧失，但再丧失5% - 10%会使基础血浆葡萄糖升至超过10毫摩尔/升。在连续65例新诊断的、无并发症的糖尿病患者（包括正常体重和肥胖患者）中，三分之一的患者经该模型分析表明，胰岛素抵抗而非β细胞缺陷是主要特征。
