PHYSIOLOGIC EVALUATION OF FACTORS CONTROLLING GLUCOSE-TOLERANCE IN MAN - MEASUREMENT OF INSULIN SENSITIVITY AND BETA-CELL GLUCOSE SENSITIVITY FROM THE RESPONSE TO INTRAVENOUS GLUCOSE
PHYSIOLOGIC EVALUATION OF FACTORS CONTROLLING GLUCOSE-TOLERANCE IN MAN - MEASUREMENT OF INSULIN SENSITIVITY AND BETA-CELL GLUCOSE SENSITIVITY FROM THE RESPONSE TO INTRAVENOUS GLUCOSE
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DOI：
10.1172/jci110398
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发表时间：
1981-01-01
影响因子：
15.9
通讯作者：
COBELLI, C
中科院分区：
文献类型：
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作者：
BERGMAN, RN;PHILLIPS, LS;COBELLI, C
在18名瘦和肥胖受试者（88-206%理想体重）中，使用最小建模技术测量胰腺反应性和胰岛素敏感性对葡萄糖耐量的定量贡献。通过2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力学，测量胰岛素分泌和作用的个体贡献。一种是胰岛素动力学模型，产生β-胰岛素受体的第1相（v φ 1）和第2相（v φ 2）响应性的参数。细胞转化为葡萄糖。另一个葡萄糖动力学模型产生胰岛素敏感性参数SI。将瘦型和肥胖型受试者分为良好（KG [Ia葡萄糖浓度与时间] > 1.5）和较低（KG < 1.5）葡萄糖耐量组。低葡萄糖耐量的病因是完全不同的瘦和肥胖的受试者。消瘦、低耐受性与胰腺功能不全有关（vphi 2比良好耐受性对照低77%[P < 0.03]），但胰岛素敏感性正常（P > 0.5）。相比之下，肥胖的低耐受性完全是由于胰岛素抵抗（SI降低60% [P < 0.01]）;胰腺反应性与瘦的、良好耐受性的对照没有不同（v φ 1：P > 0.06; v φ 2：P > 0.40）。受试者（不考虑体重）可以通过第2阶段β-γ的乘积被分为良好和较低耐受性。细胞反应性胰岛素敏感性（vphi.2.cntdot. SI）。因此，这2个因素主要负责葡萄糖耐量的总体测定。v φ 1的作用是调节其中总耐受性由v φ 2确定的那些组中的KG值。SI.这种vphi 1调节影响在胰岛素敏感（vphi 1对KG，r = 0.79）受试者中比在胰岛素抵抗（肥胖，低耐受; vphi 1对KG，r = 0.91）受试者中更显著。本研究证明了最小模型技术确定糖耐量减低病因的可行性。
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 i.v. glucose tolerance test in terms of 2 mathematical models. One, the insulin kinetics model, yields parameters of 1st-phase (.vphi.1) and 2nd phase (.vphi.2) responsiveness of the .beta.-cells to glucose. The other glucose kinetics model yields the insulin sensitivity parameter, SI. Lean and obese subjects were subdivided into good (KG [Ia glucose concentration vs. time] > 1.5) and lower (KG < 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 (.vphi.2 77% lower than in good tolerance controls [P < 0.03]), but insulin sensitivity was normal (P > 0.5). In contrast, obese lower tolerance was entirely due to insulin resistance (SI diminished 60% [P < 0.01]); pancreatic responsiveness was not different from lean, good tolerance controls (.vphi.1: P > 0.06; .vphi.2: P > 0.40). Subjects (regardless of weight) could be segregated into good and lower tolerance by the product of 2nd-phase .beta.-cell responsiveness insulin sensitivity (.vphi.2 .cntdot. SI). Thus, these 2 factors were primarily responsible for overall determination of glucose tolerance. The effect of .vphi.1 was to modulate the KG value within those groups in which overall tolerance was determined by .vphi.2 .cntdot. SI. This .vphi.1 modulating influence was more pronounced among insulin sensitive (.vphi.1 vs. KG, r = 0.79) than insulin resistant (obese, low tolerance; .vphi.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.