Hyperglycemia and insulin resistance are common in critically ill patients, even if they have not previously had diabetes. Whether the normalization of blood glucose levels with insulin therapy improves the prognosis for such patients is not known.

Intensive insulin therapy reduces morbidity and mortality in patients in surgical intensive care units (ICUs), but its role in patients in medical ICUs is unknown.

Controversy exists about the timing of the initiation of parenteral nutrition in critically ill adults in whom caloric targets cannot be met by enteral nutrition alone.

Maintenance of normoglycemia with insulin reduces mortality and morbidity of critically ill patients. Here we report the factors determining insulin requirements and the impact of insulin dose vs. blood glucose control on the observed outcome benefits. A prospective, randomized, controlled trial. A 56-bed predominantly surgical intensive care unit in a tertiary teaching hospital A total of 1,548 patients were randomly assigned to either strict normalization of blood glucose (80–110 mg/dL) with insulin infusion or the conventional approach, in which insulin is only given to maintain blood glucose levels at 180–200 mg/dL. It was feasible and safe to achieve and maintain blood glucose levels at 20 IU/hr). Between day 7 and 12, insulin requirements decreased by 40% on stable caloric intake. Brief, clinically harmless hypoglycemia occurred in 5.2% of intensive insulin-treated patients on median day 6 (2–14) vs. 0.8% of conventionally treated patients on day 11 (2–10). The outcome benefits of intensive insulin therapy were equally present regardless of whether patients received enteral feeding. Multivariate logistic regression analysis indicated that the lowered blood glucose level rather than the insulin dose was related to reduced mortality (p < .0001), critical illness polyneuropathy (p < .0001), bacteremia (p = .02), and inflammation (p = .0006) but not to prevention of acute renal failure, for which the insulin dose was an independent determinant (p = .03). As compared with normoglycemia, an intermediate blood glucose level (110–150 mg/dL) was associated with worse outcome. Normoglycemia was safely reached within 24 hrs and maintained during intensive care by using insulin titration guidelines. Metabolic control, as reflected by normoglycemia, rather than the infused insulin dose per se, was related to the beneficial effects of intensive insulin therapy.