1682-P: Factors Associated with Postprandial Suppression of Endogenous Glucose Production in People without Diabetes

Introduction and Objective: Prior work has demonstrated that α-cell dysfunction can arise independently of β-cell dysfunction and contributes to the progression of impaired glucose tolerance. While the oral minimal model can quantify insulin secretion and action, at present there is no equivalent model for glucagon. Methods: As part of a series of experiments intended to quantify glucagon’s actions on post-challenge glucose concentrations, we studied 96 non-diabetic individuals [54 ± 1.2 years (at the time of the baseline study); body mass index (BMI) 28.4 ± 0.4 Kg/M2]on 2 occasions, 3 years apart. After an overnight fast, both [6-3H] and [6,6-2H2] glucose were infused intravenously along with an oral glucose challenge, labelled with [1-13C]-glucose. This enabled measurement of meal appearance (MRa), endogenous glucose production (EGP) and glucose disappearance (Rd). Weight and body composition were measured prior to each study. Indices for insulin secretion and action were estimated using the oral minimal model. Results: The degree of suppression of EGP, calculated as the difference between fasting and nadir EGP [(14.8 ± 0.2) - (1.9 ± 0.1) μmol/kg/min], respectively, was not associated with insulin action (Si, R2 < 0.01, p = 0.74) nor with β-cell responsivity to glucose (Φ, R2 = 0.01, p = 0.22). Suppression of EGP was also unaffected by age, total body weight, BMI and peak post-challenge glucose. On the other hand, lean body mass and nadir post-challenge glucagon correlated with EGP suppression (R2 = 0.24, p = 3.2 x 10-10). As expected, MRa and Rd did not correlate with glucagon suppression. Conclusion: These data are a useful step in characterizing the EGP response to glucagon and developing a model to quantify glucagon’s actions on glucose metabolism in the postprandial period.