Oral minimal model-based estimates of insulin sensitivity in obese youth depend on oral glucose tolerance test protocol duration

Introduction: The Oral Minimal Model (OMM), a differential-equations based mathematical model of glucose-insulin dynamics, utilizes data from a frequently sampled oral glucose tolerance test (OGTT) to quantify insulin sensitivity (SI). OMM-based estimates of SI can detect differences in insulin resistance (IR) across population groups and quantify effects of clinical or behavioral interventions. These estimates of SI have been validated in healthy adults using data from OGTTs with durations from 2 to 7 h. However, data demonstrating how protocol duration affects SI estimates in highly IR populations such as adolescents with obesity are limited. Methods: A 6-h frequently sampled OGTT was performed in adolescent females with obesity. Two, 3-, and 4- hour implementations of OMM assuming an exponentially-decaying rate of glucose appearance beyond measured glucose concentrations were compared to the 6-h implementation. A 4- hour OMM implementation with truncated data (4h Tr) was also considered. Results: Data from 68 participants were included (age 15.8 ± 1.2 years, BMI 35.4 ± 5.6 kg/m2). Although SI values were highly correlated for all implementations, they varied with protocol duration (2h: 2.86 ± 3.31, 3h: 2.55 ± 2.62, 4h: 2.81 ± 2.59, 4h tr: 3.13 ± 3.14, 6h: 3.06 ± 2.85 x 10-4 dl/kg/min per U/ml). SI estimates based on 2 or 3 h of data underestimated SI values, whereas 4-h SI estimates more closely approximated 6-h SI values. Discussion: These results suggest that OGTT protocol duration should be considered when implementing OMM to estimate SI in adolescents with obesity and other IR populations.