Abstract
INTRODUCTION. Tight glycaemic control in critically ill patients may improve morbidity and mortality. The mechanism(s) is unclear but may be due to an amelioration of catabolism. This study assessed the contribution of the insulin dose to the level of glycaemia achieved, on the catabolic response. METHODS. 16 critically ill patients were studied on 2 occasions, 48 hours apart. Study 1 was within 36 hours of ICU admission (glucose 7-9mmol/L). Patients were then randomised to one of 4 groups; a) Variable insulin, glucose 4-6mmol/L (LILG), b) Variable insulin, glucose 7-9mmol/L (LIHG), c) High-dose insulin (2mU/kg/min plus requirement from study 1), blood glucose 4-6mmol/L (HILG) d)High-dose insulin, blood glucose 7-9mmol/L (HIHG). Glucose production rate (Ra) and leucine Ra (a measure of proteolysis) were measured with [6,6-2H2]glucose and [1-13C]leucine. Endogenous glucose Ra was calculated from total glucose Ra minus dextrose infusion rate. Protein turnover was compared with 12 age-matched controls. Glucose turnover was compared to 8 separate controls. RESULTS. Study 1 plasma glucose was 7.92 ± 0.45mmol/L with insulin infusion of 5.16 ± 0.77 U/hr. Study 2 glucose was 5.71 ± 0.5, 8.72 ± 0.66, 5.12 ± 0.46, 8.6 ± 0.46mmol/L in LILG, LIHG, HILG and HIHG groups; with insulin infusion rate of 3.68 ± 1.45, 2.35 ± 0.85,14.1 ± 1.68 and 17.08 ± 3.58 U/hr respectively. Endogenous glucose Ra was suppressed in study 1 compared to controls (1.62 ± 1.4 vs 8.7 ± 0.39 mumol/kg/min); P < 0.001) and remained suppressed in study 2 in all groups. Glucose Rd was higher in study 1 than the controls (24.42 ± 1.96 vs 8.7 ± 0.39 mumol/kg/min, P <0.001) and increased further (P=0.056; P<0.05) in the HILG and HIHG groups (33.58 ± 4.21 and 43.86 ± 6.84). Leucine Ra was higher in study 1 compared to controls (1.94 ± 0.15 mumol/kg/min vs 1.63 ± 0.12; P=0.058) and did not change in study 2 in any group. CONCLUSION. Amongst non-surgical ICU admissions, insulin administered to achieve lessstringent glycaemic targets suppressed glucose Ra and increased glucose uptake but leucine Ra remained higher than in control subjects. Pharmacological doses of insulin failed to reduce leucine Ra whereas glucose Rd was significantly increased. There is no evidence for benefical metabolic effects with stringent glycaemic targets.