Insulin sensitivity and hepatic glucose production in sepsis
KeywordsSeptic Patient Baseline Period Hepatic Glucose Production High Infusion Rate Stable Isotope Technique
We designed our pilot study to determine to what extent insulin influences carbohydrate metabolism and the associated thermogenesis in septic patients.
Five septic patients complying with the inclusion criteria (clinical, laboratory and haemodynamical signs of sepsis having positive blood cultures) underwent the study procedure. Illness severity was assessed using the APACHE II scoring system. Exclusion criteria were hemodynamic instability treated by administration of catecholamines and cortisol, changes in pH and lactate level, hemodialysis or CVVHD.
The glucose rate of appearance (RA) was determined using the stable isotope technique [6,6-2H2]-glucose, and tracer/tracee ratio was measured by gas chromatography–mass spectrometry (GCMS). A priming dose followed by a constant infusion of stable isotope was used to maintain stable plasma enrichment. Basal plasma glucose enrichment was measured after 3 hours of the baseline period. Two step insulin clamps each with 120-min duration were performed using a primed continuous regular insulin infusion. This provided a steady-state infusion rate of 250 IU/min/m2 for the first step, and a five times higher infusion rate for the second step. Arterial blood glucose concentration was maintained at 5 mmol/l. There were taken seven blood samples at 5-min intervals for assessment of the average glucose enrichment before the end of each clamp. A continuous recording of the indirect calorimetry was performed using a Deltatrac II throughout the baseline period of 60 min and for all steady-state periods of clamps (last 40 min of each clamp step).
Statistical analysis was not performed due to the low number of patients. Results are expressed as mean ± standard deviation at basal conditions versus steady state of each clamp. Total glucose disposal (mg/kg/min): was not calculated vs 2.57 ± 1.05 vs 4.25 ± 1.98, hepatic glucose production (mg/kg/min): 2.48 ± 0.69 vs 0.31 ± 0.53 vs 0.66 ± 0.47, energy expenditure (kJ/min): 8.23 ± 0.95 vs 8.52 ± 0.96 vs 8.99 ± 0.98, glucose oxidation (mg/kg/min): was not calculated vs 1.08 ± 0.94 vs 2.69 ± 1.45.
These preliminary data show that basal gluconeogenesis decreases in septic patients (in comparison with healthy people –literature). Further decrease of hepatic glucose production is present during both clamps, but it is not completely diminished in spite of hyperinsulinaemia.
Hyperinsulinaemia in septic patients does not completely suppress hepatic glucose production, and glucose remains the main energy substrate in sepsis.