1683-P: Quantitative Assessment and Characterization of Glucagon Secretion Rate in Individuals with and without Obesity

Introduction and Objective: Impaired suppression of glucagon secretion rate (GSR) by glucose (G) contributes to postprandial hyperglycemia in individuals with prediabetes (PD) and type 2 diabetes (T2D). A tool to quantitatively assess defects in GSR would help to better characterize the progression from PD to T2D. Here we propose a new mathematical model to estimate GSR during a Graded Glucose Infusion (GGI). This was tested in individuals with (O) and without overweight/obesity (L). Methods: Fifty-two non-diabetic subjects (51 ± 11 yrs, mean ± SD), categorized by BMI as L (< 25 kg/m2) or O (≥ 27 kg/m2), underwent a GGI, with the G infusion rate doubling every hour for 4h. Plasma glucagon and G were frequently sampled over 4h. We tested a set of models describing GSR as a function of G. The ideal model was selected based on data fit, parameter precision, and parsimony criteria. Results: The model assumed that GSR exponentially decays with increasing G. In L, GSR exhibited a higher sensitivity to G stimulus compared to O (Fig. 1, left). The G level required to suppress GSR by 50% (G50) was significantly lower in L than O (Fig. 1, right panel). Conclusion: In conclusion, our model provides a robust tool for quantifying GSR during GGI. Results confirmed that α-cell responsiveness to G is impaired in O. Further studies are needed to validate the model during more physiological postprandial conditions.