INSULIN SENSITIVITY, INSULIN-SECRETION, AND GLUCOSE EFFECTIVENESS IN OBESE SUBJECTS - A MINIMAL MODEL ANALYSIS

The aim of the present study was to estimate insulin sensitivity (SI), insulin secretion, and glucose effectiveness in 14 obese subjects who were further divided into two groups: one with normal glucose tolerance and the other with impaired glucose tolerance (IGT). Glucose tolerance was determined by criteria of the World Health Organization. All subjects were Japanese. They underwent a modified frequently sampled intravenous glucose tolerance test: glucose (300 mg/kg body weight) was administered, and insulin (20 mU/kg body weight given over 5 minutes) was infused from 20 to 25 minutes after administration of glucose. SI and glucose effectiveness at basal insulin (SG) were estimated by Bergman's minimal model method. Body mass index (33.0 +/- 1.8 v 30.9 +/- 1.5 kg/m(2), P >.05) and fasting insulin level (127.9 +/- 30.0 v 107.4 +/- 14.4 pmol/L, P >.05) were higher in obese IGT subjects than in normal obese subjects, but were not statistically significant. With regard to fasting glucose level, obese subjects with IGT (5.9 +/- 0.3 mmol/L) had significantly higher levels than those with normal glucose tolerance (5.1 +/- 0.2 mmol/L, P <.01). There was no significant difference in SI between the two groups (0.53 +/- 0.10 v 0.56 +/- 0.13 x 10(-4) . min(-1). pmol/L(-1). P >.05). Pancreatic insulin secretion expressed as the integrated area of plasma insulin above the basal level during the first 19 minutes was significantly lower in obese subjects with IGT (3,366 +/- 1.495 pmol/L min) than in those with normal glucose tolerance (16,400 +/- 4,509 pmol/L . min, P <.05). Glucose disappearance rate ([K-G] 1.03 +/- 0.12 min(-1)), SG (0.013 +/- 0.002 min(-1)), and glucose effectiveness at zero insulin ([GEZI] 0.007 +/- 0.002 min(-1)) were significantly lower in obese subjects with IGT than in those with normal glucose tolerance (K-G, 2.11 +/- 0.25 min(-1), P <.01; SG, 0.022 +/- 0.003 min(-1), P <.01; GEZI, 0.017 +/- 0.003 min(-1), P <.01). Thus, the risk factor for worsening glucose tolerance in obese subjects is partially explained by the derangements in SG and GEZI and the impairment in B-cell function to adapt to insulin resistance. This is the first description that the impairments in both insulin secretion and glucose effectiveness but not insulin resistance may worsen glucose tolerance in obese subjects. Copyright (C) 1995 by W.B. Saunders Company