Differences Between the Tolbutamide-Boosted and the Insulin-Modified Minimal Model Protocols

Abstract

The insulin-modified frequently sampled Intravenous glucose tolerance test (FSIGTT) with minimal model analysis (MINMOD) was compared with the tolbutamide protocol and the glucose clamp in 35 nondiabetic subjects (age 38 ± 2 years [mean ± SE], BMI 27.2 ± 0.9 kg/m2). Each subject underwent two FSIGTTs, one with tolbutamide (300 mg) and the other with insulin (0.03 U/kg) and a euglycemic hyperinsulinemic clamp (40 mU · m−2 · min−1). Insulin sensitivity was determined from each FSIGTT with MINMOD and from the clamp. Insulin sensitivity indexes (SI) from the two FSIGTTs were significantly correlated (r = 0.77, P < 0.001), but SI(insuiin) was 29 ± 4% lower than SI(toibutamide). Both SI(insuiin) and Sictoibutamide) correlated significantly with SI(ciamp) (r = 0.70 and 0.71, P < 0.001 for each). Expressed in the same units (dl/min per µU/ml), SI(toibutamide) was on average 13 ± 6% lower than SI(ciamp) (4.51 ± 0.40 vs. 5.36 ± 0.36 × 10−2, P = 0.009), whereas SI(insulin) Was 44 ± 4% lower. SG(tolbutamide) and SG(insulin) were not different (1.88 ± 0.10 vs. 2.01 ± 0.09 × 10−2 min−1, P = 0.167) and were significantly correlated (r = 0.50, P = 0.002). Thus, insulin sensitivity estimates from both protocols correlate significantly with each other and with the clamp. They are quantitatively discrepant, however, possibly due to differences in the route of insulin delivery, saturation of insulin action, and/or tolbutamide-induced proinsulin release. Data obtained from these two MINMOD protocols are not directly comparable, and the same protocol must be used in any single cross-sectional or longitudinal study.