262-OR: Postprandial Glucagon Metabolism in Type 1 Diabetes

Abstract

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 Disclosure F. Ruchi: None. Y. R. Yadav: None. M. Schiavon: None. A. Weaver: None. C. Cobelli: None. C. Dalla man: Research Support; Self; Becton, Dickinson and Company, Sanofi-Aventis Deutschland GmbH. R. Basu: None. A. Basu: None. Funding National Institutes of Health (DK085516 to A.B.), (DK029953 to R.B.); National Mouse Metabolic Phenotyping Center (DK059637); Vanderbilt Diabetes Research and Training Center (DK020593)