Advantages of the single delay model for the assessment of insulin sensitivity from the intravenous glucose tolerance test

BACKGROUND: The Minimal Model, (MM), used to assess insulin sensitivity (IS) from Intra-Venous Glucose-Tolerance Test (IVGTT) data, suffers from frequent lack of identifiability (parameter estimates with Coefficients of Variation (CV) less than 52%). The recently proposed Single Delay Model (SDM) is evaluated as a practical alternative. METHODS: The SDM was applied to 74 IVGTTs from lean (19), overweight (22), obese (22) and morbidly obese (11) subjects. Estimates from the SDM (K(xgI)) were compared with the corresponding MM (S(I)), 1/HOMA-IR index and Euglycemic-Hyperinsulinemic Clamp (M-EHC over 7 subjects) estimates. RESULTS: K(xgI )was identifiable in 73 out of 74 subjects (CV = 69% in the 74(th )subject) and ranged from 1.25 × 10(-5 )to 4.36 × 10(-4)min(-1)pM(-1); S(I )CV was >52% in 36 subjects (up to 2.36 × 10(9)%) and presented 18 extreme values (≤ 1.5 × 10(-12 )or ≥ 3.99). K(xgI )correlated well with 1/HOMA-IR (r = 0.56, P < 0.001), whereas the correlations K(xgI)-S(I )and 1/HOMA-IR-S(I )were high (r = 0.864 and 0.52 respectively) and significant (P < 0.001 in both cases) only in the non-extreme S(I )sub-sample (56 subjects). Correlations K(xgI )vs. M-EHC and S(I )vs. M-EHC were positive (r = 0.92, P = 0.004 and r = 0.83, P = 0.02 respectively). K(xgI )decreased for higher BMI's (P < 0.001), S(I )significantly so only over the non-extreme-S(I )sub-sample. The Acute Insulin Response Index was also computed and the expected inverse (hyperbolic) relationship with the K(xgI )observed. CONCLUSIONS: Precise estimation of insulin sensitivity over a wide range of BMI, stability of all other model parameters, closer adherence to accepted physiology make the SDM a useful alternative tool for the evaluation of insulin sensitivity from the IVGTT.