BOTH A REDUCED ACUTE INSULIN-RESPONSE TO GLUCOSE AND LOWER GLUCOSE EFFECTIVENESS ARE RESPONSIBLE FOR THE WORSENING OF INTRAVENOUS GLUCOSE-TOLERANCE IN HEALTHY-SUBJECTS INDEPENDENTLY OF THE DEGREE OF OBESITY

The effects of the acute insulin response to glucose (AIRS), insulin s ensitivity (S-I), and glucose effectiveness at zero insulin (GEZI) on intravenous glucose tolerance were studied in 94 non elderly healthy s ubjects with a wide range of body mass index (BMI). Conrad's coefficie nt of glucose assimilation (K-G) was calculated between 10 and 19 minu tes of an intravenous glucose tolerance test. Both S-I and GEZI were e stimated using Bergman's minimal model. AIRS was calculated as the are a under the insulin curve above basal between 0 and 10 minutes, and th e suprabasal insulin effect was determined by the product of S-I x AIR S. Stepwise multiple regression showed that the combined effect of S-I x AIRg and GEZI explained 67% of the K-G index variance. Division of the sample into tertiles according to K-G shows that subjects with the lowest K-G (K-G < 1.32 min(-1)) had the lowest AIRg (2,832 +/- 1,362 v 6,510 +/- 4,410 [pmol.L-1] min, P = .0005), the lowest GEZI (0.092 /- 0.06 v 0.179 +/- 0.09 min(-1) P = .0004), and the lowest S-I x AIRg (0.014 +/- 0.008 v 0.022 +/- 0.01 min(-1), P = .00001), and were the oldest (41 +/- 10 v 31 +/- 10 years, P = .002) compared with subjects with the highest K-G (K-G > 1.8 min(-1)). However, no differences in S -I (4.86 +/- 4.6 v 6.5 +/- 3.7 min(-1) [pmol.L-1],(-1) NS) or BMI (29. 6 +/- 5.0 v 26.6 +/- 5.9 kg.m(-2), NS) were observed. These results di d not vary when lean and obese subjects were analyzed separately. Age correlated significantly only with S-I x AIRg. In conclusion, although the main factors that determine intravenous glucose tolerance are the suprabasal insulin effect and GEZI, worsening of the K-G index depend s on inadequate insulin secretion for the degree of insulin sensitivit y and lower non-insulin-mediated glucose uptake, Age seems to be anoth er factor in the worsening of intravenous glucose tolerance through a lower suprabasal insulin effect. Copyright (C) 1998 by W.B. Saunders C ompany.