PHYSIOLOGIC EVALUATION OF FACTORS CONTROLLING GLUCOSE-TOLERANCE IN MAN - MEASUREMENT OF INSULIN SENSITIVITY AND BETA-CELL GLUCOSE SENSITIVITY FROM THE RESPONSE TO INTRAVENOUS GLUCOSE

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.