Hyperglycemia

in response to critical illness has longbeen associated with adverse outcomes. Large ob-servational studies have recently confirmed and fine-tuned this association, reporting the lowest risk of death with blood glucose levels roughly between 5 and 7 mmol/L or between 6 and 8 mmol/L for patients with diabetes melli-tus.1,2 This association is thought to be causal based on poten-tial glucose toxicity in the context of ischemia–reperfusion. Studies in patients and animals support the hypothesis of tox-icity induced by excess glucose, specifically toxicity to the mitochondria of cells that take up glucose independent of in-sulin and in proportion to the circulating levels of glucose.3–5 However, the level at which blood glucose becomes toxic in the clinical context of critical illness is unclear. Several studies with heterogeneous designs and outcome measures have tested the hypothesis that tight control of blood glucose levels improves outcomes in critically ill patients. Th