Abstract
Stress-induced hyperglycemia is a significant problem in critically ill patients, for whom the severity of hyperglycemia and insulin resistance reflects the risk of death. We recently demonstrated that strict maintenance of normoglycemia with intensive insulin therapy during intensive care reduced the morbidity and mortality of surgical ICU patients [1]. Normal cells respond to hyperglycemia by downregulating the insulin-independent glucose transporters (GLUT1, GLUT2 and GLUT3), thereby protecting themselves against passive glucose overload. Insulin is known to upregulate muscle GLUT4 expression, required for controlled glucose uptake in the muscle. We investigated expression levels of these four GLUTs in critical illness and assessed the impact of intensive insulin therapy. We examined mRNA expression levels with real-time RT-PCR in muscle and liver tissue of 36 nonsurvivors, who had been randomized to intensive (normoglycemic) or conventional (hyper-glycemic) insulin therapy and who were comparable for age and severity, duration and type of critical illness. The mean blood glucose levels were 5.6 ± 0.4 and 9.9 ± 0.9 mmol/l (P < 0.001) on a median daily insulin dose of 44.2 and 14.4 IU (P = 0.005), respectively. For comparison, we studied tissue harvested from patients undergoing acute surgical stress as well as tissue from healthy controls. We demonstrated that in both the liver and muscle of patients with prolonged critical illness, the high-affinity insulin-independent glucose transporters GLUT1 and GLUT3 are substantially up-regulated. In muscle the GLUT4 expression is reduced, reflecting insulin resistance. In liver, intensive insulin therapy suppresses GLUT2 with no effect on the other GLUTs. In muscle, intensive insulin therapy downregulates GLUT1 and GLUT3 expression whereas GLUT4 expression is normalized. In conclusion, expression of GLUT1 and GLUT3 is upregulated and GLUT2 expression is normal in prolonged critical illness, a constellation that may predispose cells to glucose overload and toxicity, and that can be beneficially affected by intensive insulin therapy. Expression of GLUT4, by far the most dominantly expressed transporter in muscle, is low in the critically ill and is normalized by intensive insulin therapy. Together, these findings may offer an explanation for the high vulnerability to glucose toxicity during critical illness and how intensive insulin therapy may prevent this.
Highlights
Tight blood glucose (BG) control has been shown to videos of the alveolar dynamics
1Royal Brompton Hospital, London, UK; 2Medical University Graz, observation from mechanical deformation due to the tip of the Austria; 3Charles University Hospital, Prague, Czech Republic; endoscope we developed a flushing catheter that continuously
Taurocholic acid into the pancreatic duct. This allowed us to separate and to determine the specific role of pancreatic blood vs Introduction In the frame of protective lung ventilation, alveolar normal blood on the expression of injury evidenced during isolated biomechanics become more and more the focus of scientific lung reperfusion
Summary
Tight blood glucose (BG) control has been shown to videos of the alveolar dynamics. The thorax remains intact.decrease morbidity and mortality in critically ill patients [1] but is Results Figure 1 shows a tissue area after lavage of 0.8 mm difficult to achieve using standard insulin infusion protocols. Results Patient characteristics (mean ± SD): age 57.4 ± 15.4 years, 28 female, 52 male, APACHE II score 28.2 ± 6.6; number of organ failures 4.0 ± 1.12; preceding ICU period 8.5 ± 9.3 days; continuous sedation with midazolam 31.2 ± 34.2 mg/hour, fentanyl 0.12 ± 0.08 mg/hour, propofol 45.6 ± 105.2 mg/hour; sedation assessment according to RS 5.65 ± 0.63, CPS 5.15 ± 1.67, CKS 0.65 ± 0.69, CS 9.34 ± 2.13 und LSS 1.78 ± 1.69, RASS –4.50 ± 1.27, FiO2 0.52 ± 0.17, PEEP 8.2 ± 2.4 cmH2O, ventilatory frequency 20.5 ± 4.8/min, pressure control 16.8 ± 4.4 cmH2O, tidal volume 540 ± 115 ml, TVV 2525.6 ± 11,366 ml (minimum 1.52; maximum 91,586). We hypothesized that S100β levels correlate with this tumor’s preoperative characteristics and with perioperative neurological injury despite its supratentorial location and non-neural origin
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