DIFFERENCES BETWEEN THE TOLBUTAMIDE-BOOSTED AND THE INSULIN-MODIFIED MINIMAL MODEL PROTOCOLS

The insulin-modified frequently sampled intravenous glucose tolerance test (FSIGTT) with minimal model analysis (MINMOD) was compared with t he tolbutamide protocol and the glucose clamp in 35 nondiabetic subjec ts (age 38 +/- 2 years [mean +/- SE], BMI 27.2 +/- 0.9 kg/m(2)). Each subject underwent two FSIGTTs, one with tolbutamide (300 mg) and the o ther with insulin (0.03 U/kg) and a euglycemic hyperinsulinemic clamp (40 mU.m(-2).min(-1)). Insulin sensitivity was determined from each FS IGTT with MINMOD and from the clamp. Insulin sensitivity indexes (S-I) from the two FSIGTTs were significantly correlated (r = 0.77, P < 0.0 01), but S-I(insulin) was 29 +/- 4% lower than S-I(tolbutamide). Both SI(insulin) and SI(tolbutamide) correlated significantly with S-I(clam p) (r = 0.70 and 0.71, P < 0.001 for each). Expressed in the same unit s (dl/min per mu U/ml), S-I(tolbutamide) Was On average 13 +/- 6% lowe r than S-I(clamp) (4.51 +/- 0.40 vs. 5.36 +/- 0.36 x 10(-2), P = 0.009 ), whereas S-I(insulin) was 44 +/- 4% lower. S-G(tolbutamide) and S-G( insulin) were not different (1.88 +/- 0.10 vs. 2.01 +/- 0.09 x 10(-2) min(-1), P = 0.167) and were significantly correlated (r = 0.50, P = 0 .002). Thus, insulin sensitivity estimates from both protocols correla te significantly with each other and with the clamp. They are quantita tively discrepant, however, possibly due to differences in the route o f insulin delivery saturation of insulin action, and/or tolbutamide-in duced proinsulin release. Data obtained from these two MINMOD protocol s are not directly comparable, and the same protocol must be used in a ny single cross-sectional or longitudinal study.