The effect of insulin dose and level of glycaemia on catabolism in critically ill patients

Background and Aims: Evidence suggests that tight glycaemic control in critically ill patients can improve morbidity and mortality. The mechanism( s) underlying its benefit remain speculative but might involve an amelioration of catabolism. This study was designed to differentiate the contribution of the insulin dose to the level of glycaemia achieved, on the catabolic response. Materials and Methods: A prospective study was conducted in 16 critically ill patients. Subjects with diabetes mellitus, pancreatitis, or liver disease were excluded. Patients were studied on 2 occasions, 48 hours apart. The baseline study was within 36 hours of admission to the ICU with blood glucose at 7–9 mmol/L. Patients were then randomised to one of four groups: Variable insulin with plasma glucose 4–6 mmol/L (LILG); Variable insulin with plasma glucose 7–9mmol/L (LIHG); High-dose insulin (2mU· kg–1·min–1 plus requirement from baseline) and variable dextrose to maintain glucose 4–6 mmol/L (HILG); High-dose insulin and variable dextrose to maintain glucose 7–9 mmol/L (HIHG). Glucose production rate (Ra) and leucine Ra (a measure of protein degradation) were measured with a 3-hour infusion of [6,62H2]glucose and [1-13C]leucine. Steady state sampling was performed at 150 to 180 mins. Endogenous glucose Ra was calculated by subtracting the dextrose infusion rate from total glucose Ra. Leucine oxidation rate (Ox) was calculated from CO2 enrichment and CO2 production rate.Non-oxidative leucine disposal (a measure of protein synthesis) was calculated as leucine Ra minus leucine Ox. Non-esterified fatty acid concentrations provide an estimate of lipolysis. Results: Protein turnover data (mean±SEM) was compared with 12 fasted age-matched controls. Glucose turnover data was compared to a separate control group of 8 subjects. Conclusions: Amongst non-surgical ICU admissions, the use of insulin to achieve less-stringent glycaemic targets was able to suppress glucose Ra and lipolysis and increase glucose uptake. No further suppression of glucose Ra was found with high dose insulin or with tighter glycaemic control. Leucine Ra was not decreased, even by pharmacological doses of insulin, whereas glucose Rd was significantly increased in the HILG and HIHG groups. These results suggest that the use of insulin to achieve normoglycaemia in the critical care setting does not promote whole body protein anabolism