The effect of insulin therapy on glucose production rate, glucose uptake, lipolysis and proteolysis in non-surgical ICU patients

Background and aims: Recent data suggest that the use of insulin to maintain intensive glycaemic control amongst surgical ICU patients can improve morbidity and mortality. The value of this procedure in non-surgical patients is not known. Current insulin therapy for non-surgical patients in many ICUs aims to keep plasma glucose below 9 mmolll. The effect of this insulin therapy protocol on the catabolic response of critical illness, characterised by increased glucose production, increased lipolysis and proteolysis is unknown. Materials and methods: A prospective study was conducted in seven critically ill non-surgical patients (6M:1F, age 64±2.72 years; BMI 24.77 ± 0.77 kg/m2) within 36 hours of their admission to the ICU. Patients with diabetes mellitus, pancreatitis, oral steroid use within 1 month of entering the ICU, or liver disease (LFTs > twice normal range), were excluded. All patients were receiving 20% dextrose intravenously to provide 25kcal.kg-lday-l. Insulin was infused at a variable rate to maintain plasma glucose below 9 mmollL. Glucose production rate (Ra) and rate of uptake (Rd), glycerol Ra (a measure oflipolysis) and leucine Ra (a measure of proteolysis) were measured with a 3 hour primed infusion of [6,6- 2H2]glucose (l70mg, 1.7mg.min-I), [2H5]glycerol (0.15mg/kg, 0.61mg· kg-lhc1) and [l-l3C]leucine (1 mg/kg, 1 mg.kg-lhcl). Steady state sampling was performed at 150 to 180 minutes. Results are compared with fasting values from an age and weight matched healthy control group. All data presented are mean ± SEM. Results: The mean APACHE II score on the day of study was 15.43 ± 1.87. Mean plasma glucose at steady state was 7.95±0.73mmol· L-l. The mean glucose infusion rate was 22.83 ± 0.74 f.lmol.kg-lmin-l. The average insulin infusion rate was 4.31 ±0.73 U.hr-l which achieved plasma insulin concentrations of 655.21 ± 181.38 pmol.L-I. Endogenous glucose Ra was decreased (2.24±3.02f.lmol.kg-lmin-l, p<0.03) and glucose Rd was increased (25.08±3.07f.lmol.kg-lmin-l, P<O.OOOl) compared to fasting glucose Ra/Rd in the control subjects (8.7 ± 0.39 f.lmol.kg-lmin-l). Glycerol Ra and concentration (1.66±0.23f.lmol.kg-lmin-1 and 46.72 ± 12.25 f.lmol.L-1 respectively) were reduced (p<0.02, P=0.07) compared to the control subjects (2.89 ± 0.47 f.lmol.kg-lmin-l and 70.03 ± 8.53 f.lmol.L -1). Plasma NEFA concentrations were very low at 0.10 ±0.03 mmol.L-1 compared to fasting values in the control subjects (0.71 ±0.09mmol.L-I, P