Postprandial Glucagon Metabolism in Healthy and Type 1 Diabetes

Early postprandial glucagon concentrations are higher in type 1 diabetes (T1D) than in individuals with no diabetes (ND). To determine the cause, we infused stable [13C9,15N1]glucagon before, during, and after a mixed meal in 16 ND and 16 T1D individuals to measure gluca-gon turnover. In a subcohort of 9 ND and 12 T1D individ-uals, we estimated [13C9,15N1]glucagon kinetics during steady state. A linear, single-compartment model described [13C9,15N1]glucagon kinetics and allowed precise estimation of the volume of distribution (VD) and clearance rate (CL). Model parameters were similar between groups, with the VDof [13C9,15N1]glucagon at 42.1 ± 3.3 mL/kg, implying that [13C9,15N1]glucagon distributes in a single compartment and with VDapproximating the plasma volume and CL at 10.6 ± 0.9 mL/kg/min. Higher early (0–120 min after meal ingestion) postprandial glucagon concentrations (1,907.9 ± 373.4 vs. −93.6 ± 240.5 pg/mL · 120 min P < 0.001) observed in T1D was due to higher rates of glucagon appearance (3.39 ± 2.8 vs. −3.95 ± 2.0 ng/kg · 120 min, P < 0.04) and disappearance (2.13 ± 2.6 vs. −5.28 ± 2.1 ng/kg · 120 min, P < 0.04) compared with ND. We have determined postprandial glucagon turnover in humans and have demonstrated that changes in postprandial glucagon concentrations in T1D are due to increased rates of glucagon turnover during the early postprandial period.