title: 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 x m(-2) x min(-1)). Insulin sensitivity was determined from each FSIGTT with MINMOD and from the clamp. Insulin sensitivity indexes (S(I)) from the two FSIGTTs were significantly correlated (r = 0.77, P < 0.001), but S(I(insulin)) was 29 +/- 4% lower than S(I(tolbutamide)). Both S(I(insulin)) and S(I(tolbutamide)) correlated significantly with S(I(clamp)) (r = 0.70 and 0.71, P < 0.001 for each). Expressed in the same units (dl/min per pU/ml), S(I(tolbutamide)) was on average 13 +/- 6% lower 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 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.
authors.affiliation: Department of Medicine, University of Southern California Medical School, Los Angeles 90033, USA. saad@hsc.usc.edu
authors.forename: M F
authors.initials: MF
authors.lastname: Saad
authors.forename: G M
authors.initials: GM
authors.lastname: Steil
authors.forename: W W
authors.initials: WW
authors.lastname: Kades
authors.forename: M F
authors.initials: MF
authors.lastname: Ayad
authors.forename: W A
authors.initials: WA
authors.lastname: Elsewafy
authors.forename: R
authors.initials: R
authors.lastname: Boyadjian
authors.forename: S D
authors.initials: SD
authors.lastname: Jinagouda
authors.forename: R N
authors.initials: RN
authors.lastname: Bergman
mesh_terms: D000328:Adult; D001786:Blood Glucose / Q000032:analysis* / Q000378:metabolism; D003198:Computer Simulation; D015309:Glucose Clamp Technique; D005951:Glucose Tolerance Test; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage* / Q000097:blood / Q000378:metabolism; D007328:Insulin / Q000008:administration & dosage / Q000097:blood* / Q000378:metabolism; D008297:Male; D008954:Models, Biological; D011237:Predictive Value of Tests; D011384:Proinsulin / Q000097:blood / Q000378:metabolism; D013997:Time Factors; D014044:Tolbutamide / Q000008:administration & dosage*
chemical_list: D001786:Blood Glucose; D007004:Hypoglycemic Agents; D007328:Insulin; D011384:Proinsulin; D014044:Tolbutamide