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  • Title: Impact of C-Peptide Status on the Response of Glucagon and Endogenous Glucose Production to Induced Hypoglycemia in T1DM.
    Author: Zenz S, Mader JK, Regittnig W, Brunner M, Korsatko S, Boulgaropoulos B, Magnes C, Raml R, Narath SH, Eller P, Augustin T, Pieber TR.
    Journal: J Clin Endocrinol Metab; 2018 Apr 01; 103(4):1408-1417. PubMed ID: 29408994.
    Abstract:
    CONTEXT: Complete loss of β-cell function in patients with type 1 diabetes mellitus (T1DM) may lead to an increased risk of severe hypoglycemia. OBJECTIVE: We aimed to determine the impact of C-peptide status on glucagon response and endogenous glucose production (EGP) during hypoglycemia in patients with T1DM. DESIGN AND SETTING: We conducted an open, comparative trial. PATIENTS: Ten C-peptide positive (C-pos) and 11 matched C-peptide negative (C-neg) patients with T1DM were enrolled. INTERVENTION: Plasma glucose was normalized over the night fast, and after a steady-state (baseline) plateau all patients underwent a hyperinsulinemic, stepwise hypoglycemic clamp with glucose plateaus of 5.5, 3.5, and 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 a stable isotope tracer technique. MAIN OUTCOME MEASURE: Impact of C-peptide status on glucagon response and EGP during hypoglycemia. RESULTS: 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 ± standard deviation) 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 hypoglycemia revealed significantly higher glucagon concentrations in C-pos than in C-neg patients. EGP was significantly higher in C-pos patients at hypoglycemia (2.5 mmol/L) compared with C-neg patients. CONCLUSIONS: Glucagon concentrations and EGP during hypoglycemia were more pronounced in C-pos than in C-neg patients, which indicates that preserved β-cell function may contribute to counterregulation during hypoglycemia in patients with T1DM.
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