262-OR: Postprandial Glucagon Metabolism in Type 1 Diabetes

Inappropriately elevated postprandial (PP) glucagon concentrations contribute to hyperglycemia in type 1 diabetes (T1D). To define the underlying mechanisms, we infused ¹³C¹⁵N glucagon tracer in healthy and T1D subjects during a mixed meal (75 gm carb, 15% fat, 35% protein; 8 kcal/kg) to estimate PP glucagon turnover. We show data from 12 healthy (age 26 ± 6 yrs, BMI 24.6±2.8 kg/m², fasting plasma glucose 4.8±0.3 mM, HbA1c 5.0±0.3%) and 4, C-peptide negative T1D (age 37 ± 15 yrs, BMI 27.5 ± 2.3 kg/m², fasting plasma glucose 11.1 ± 2.9 mM, HbA1c 7.7 ± 0.9%) subjects completed thus far. Arterialized venous samples were drawn periodically for measurements of ¹³C¹⁵N glucagon (tandem mass spectrometry), glucagon (Mercodia), and glucose (YSI) concentrations throughout the study. Systemic glucagon turnover was calculated by non-steady-state Steele’s equation after determining volume of distribution of glucagon. Integrated PP glucagon concentrations were higher (p<0.01) in T1D subjects during the first 3 hours after meal ingestion. Integrated rates of glucagon appearance and disappearance were numerically higher in T1D than healthy subjects during 0-180 min after meal. However, when adjusted for prevailing plasma glucagon concentrations, integrated glucagon clearance was lower (p<0.001) in T1D subjects. These data suggest that higher rates of glucagon appearance and lower glucagon clearance both contribute to elevated PP glucagon concentrations in T1D.

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