Evaluation of Insulin Sensitivity and β-Cell Function Indexes Obtained From Minimal Model Analysis of a Meal Tolerance Test

Evaluation of Insulin Sensitivity and β-Cell Function Indexes Obtained From Minimal Model Analysis of a Meal Tolerance Test Garry M. Steil 1 , Chi-min Hwu 2 , Robert Janowski 1 , Farzam Hariri 2 , Sujata Jinagouda 2 , Christine Darwin 2 , Sameh Tadros 2 , Kerstin Rebrin 1 and Mohammed F. Saad 2 1 Medtronic MiniMed, Northridge, California 2 Department of Medicine, School of Medicine, University of California at Los Angeles, Los Angeles, California Address correspondence and reprint requests to Garry M. Steil, Medtronic MiniMed, 18000 Devonshire St., Northridge, CA 91325. E-mail: garry.steil{at}Medtronic.com Abstract Modeling analysis of glucose, insulin, and C-peptide following a meal has been proposed as a means to estimate insulin sensitivity ( S i ) and β-cell function from a single test. We compared the model-derived meal indexes with analogous indexes obtained from an intravenous glucose tolerance test (IVGTT) and hyperglycemic clamp (HGC) in 17 nondiabetic subjects (14 men, 3 women, aged 50 ± 2 years [mean ± SE], BMI 25.0 ± 0.7 kg/m 2 ). S i estimated from the meal was correlated with S i estimated from the IVGTT and the HGC ( r = 0.59 and 0.76, respectively; P < 0.01 for both) but was ∼2.3 and 1.4 times higher ( P < 0.05 for both). The meal-derived estimate of the β-cell’s response to a steady-state change in glucose (static secretion index) was correlated with the HGC second-phase insulin response ( r = 0.69; P = 0.002), but the estimated rate-of-change component (dynamic secretion index) was not correlated with first-phase insulin release from either the HGC or IVGTT. Indexes of β-cell function obtained from the meal were significantly higher than those obtained from the HGC. In conclusion, insulin sensitivity and β-cell indexes derived from a meal are not analogous to those from the clamp or IVGTT. Further work is needed before these indexes can be routinely used in clinical and epidemiological studies. FFA, free fatty acid FSD, fractional SD HGC, hyperglycemic clamp IVGTT, intravenous glucose tolerance test Footnotes M.F.S. has received research support from Medtronic MiniMed. Accepted February 17, 2004. Received November 3, 2003. DIABETES