Impact of C-Peptide Status on the Response of Glucagon and Endogenous Glucose Production to Induced Hypoglycaemia in T1D
Sabine Zenz, Julia K. Mader, Werner Regittnig, Martina Brunner, Stefan Korsatko, Beate Boulgaropoulos, Christoph Magnes, Reingard Raml, Sophie H. Narath, Philipp Eller, Thomas Augustin, Thomas R. Pieber
The Journal of Clinical Endocrinology & Metabolism , 2/2018
Complete loss of beta-cell function in type 1 diabetes (T1DM) patients may lead to an increased risk of severe hypoglycaemia.
We aimed to determine the impact of C-peptide status on glucagon response and endogenous glucose production (EGP) during hypoglycaemia in T1DM patients.
We conducted an open, comparative trial.
10 C-peptide positive (C-pos) and 11 matched C-peptide negative (C-neg) T1DM patients were enrolled.
Plasma glucose was normalised over the night fast and after a steady-state (baseline) plateau all patients underwent a hyperinsulinaemic, stepwise hypoglycaemic clamp with glucose plateaus of 5.5, 3.5, 2.5 mmol/l and a recovery phase of 4.0 mmol/l. Blood glucagon was measured with a specific and highly sensitive glucagon assay. EGP was determined with stable isotope tracer technique.
MAIN OUTCOME MEASURE:
Impact of C-peptide status on glucagon response and EGP during hypoglycaemia.
Glucagon concentrations were significantly lower in C-pos and C-neg patients than previously reported. At baseline, C-pos patients had higher glucagon concentrations than C-neg patients (8.39±4.6 vs. 4.19±2.4 pmol/l, p=0.016, mean±SD), but comparable EGP rates (2.13±0.2 vs. 2.04±0.3 mg/kg/min, p< 0.391). In both groups, insulin suppressed glucagon levels, but hypoglycaemia revealed significantly higher glucagon concentrations in C-pos than in C-neg patients. EGP was significantly higher in C-pos patients at hypoglycaemia(2.5mmol/l) compared to C-neg patients.
Glucagon concentrations and EGP during hypoglycaemia were more pronounced in C-pos than in C-neg patients which indicates that preserved beta-cell function may contribute to counter-regulation during hypoglycaemia in type 1 diabetes patients.