Impact of C-Peptide Status on the Response of Glucagon and Endogenous Glucose Production to Induced Hypoglycaemia in T1D

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. 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.