Bergman R N, Phillips L S, Cobelli C
J Clin Invest. 1981 Dec;68(6):1456-67. doi: 10.1172/jci110398.
The quantitative contributions of pancreatic responsiveness and insulin sensitivity to glucose tolerance were measured using the "minimal modeling technique" in 18 lean and obese subjects (88-206% ideal body wt). The individual contributions of insulin secretion and action were measured by interpreting the dynamics of plasma glucose and insulin during the intravenous glucose tolerance test in terms of two mathematical models. One, the insulin kinetics model, yields parameters of first-phase (phi 1) and second-phase (phi 2) responsivity of the beta-cells to glucose. The other glucose kinetics model yields the insulin sensitivity parameters, SI. Lean and obese subjects were subdivided into good (KG greater than 1.5) and lower (KG less than 1.5) glucose tolerance groups. The etiology of lower glucose tolerance was entirely different in lean and obese subjects. Lean, lower tolerance was related to pancreatic insufficiency (phi 2 77% lower than in good tolerance controls [P less than 0.03]), but insulin sensitivity was normal (P greater than 0.5). In contrast, obese lower tolerance was entirely due to insulin resistance (SI diminished 60% [P less than 0.01]); pancreatic responsiveness was not different from lean, good tolerance controls (phi 1: P greater than 0.06; phi 2: P greater than 0.40). Subjects (regardless of weight) could be segregated into good and lower tolerance by the product of second-phase beta-cell responsivity and insulin sensitivity (phi 2 . SI). Thus, these two factors were primarily responsible for overall determination of glucose tolerance. The effect of phi 1 was to modulate the KG value within those groups whose overall tolerance was determined by phi 2 . SI. This phi 1 modulating influence was more pronounced among insulin sensitive (phi 1 vs. KG, r = 0.79) than insulin resistant (obese, low tolerance; phi 1 vs. KG, r = 0.91) subjects. This study demonstrates the feasibility of the minimal model technique to determine the etiology of impaired glucose tolerance.
采用“最小模型技术”对18名体重正常和肥胖的受试者（体重为理想体重的88%-206%）的胰腺反应性和胰岛素敏感性对葡萄糖耐量的定量贡献进行了测定。通过用两个数学模型解释静脉葡萄糖耐量试验期间血浆葡萄糖和胰岛素的动态变化，来测量胰岛素分泌和作用的个体贡献。一个是胰岛素动力学模型，可得出β细胞对葡萄糖的第一相（φ1）和第二相（φ2）反应性参数。另一个葡萄糖动力学模型可得出胰岛素敏感性参数SI。体重正常和肥胖的受试者被分为葡萄糖耐量良好（KG大于1.5）和较差（KG小于1.5）两组。体重正常和肥胖受试者葡萄糖耐量较差的病因完全不同。体重正常者葡萄糖耐量较差与胰腺功能不全有关（φ2比耐量良好的对照组低77%[P<0.03]），但胰岛素敏感性正常（P>0.5）。相比之下，肥胖者葡萄糖耐量较差完全是由于胰岛素抵抗（SI降低60%[P<0.01]）；胰腺反应性与体重正常、耐量良好的对照组无差异（φ1：P>0.06；φ2：P>0.40）。受试者（无论体重如何）可通过第二相β细胞反应性和胰岛素敏感性的乘积（φ2·SI）分为耐量良好和较差两组。因此，这两个因素是总体葡萄糖耐量测定的主要决定因素。φ1的作用是在那些总体耐量由φ2·SI决定的组内调节KG值。这种φ1调节影响在胰岛素敏感的受试者（φ1与KG，r=0.79）中比胰岛素抵抗的受试者（肥胖、耐量低；φ1与KG，r=0.91）中更明显。本研究证明了最小模型技术在确定葡萄糖耐量受损病因方面的可行性。
