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 ( $S_I$ ). OMM-based estimates of $S_I$ can detect differences in insulin resistance (IR) across population groups and quantify effects of clinical or behavioral interventions. These estimates of $S_I$ have been validated in healthy adults using data from OGTTs with durations from 2 to 7 h. However, data demonstrating how protocol duration affects $S_I$ 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 $S_I$ 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). $S_I$ estimates based on 2 or 3 h of data underestimated $S_I$ values, whereas 4-h $S_I$ estimates more closely approximated 6-h $S_I$ values.

Discussion: These results suggest that OGTT protocol duration should be considered when implementing OMM to estimate $S_I$ in adolescents with obesity and other IR populations.