Mechanisms of insulin-induced alterations in metabolism during critical illness.

Through the explosion of therapeutic possibilities within the setting of intensive care medicine, patients can nowadays survive previously lethal disease states. Specific endocrine approaches to critical illness have always been limited to sporadic trials and isolated schools advocating rigorous metabolic control. This is in stark contrast with the boom of therapeutic possibilities for diabetes mellitus and coronary artery disease, where tight glycemic and lipemic control are now common practice. The Diabetes and Insulin-Glucose Infusion in Acute Myocardial Infarction (DIGAMI) [1] showed an improved outcome of diabetic patients with myocardial infarction upon ‘moderate’ blood glucose control. As a further step, a large prospective, randomized, controlled trial was set up to examine the effect of ‘strict’ glycemic control below 6.1 mmol/l (110 mg/dl) with exogenous insulin on the mortality and morbidity of critically ill patients [2], both diabetic and nondiabetic. Over a 1-year period, 1,548 mechanically ventilated patients admitted to the intensive care unit (ICU), predominantly after extensive surgery or trauma, were randomly allocated to either intensive insulin therapy with blood glucose levels kept tightly between 4.5 and 6.1 mmol/l (80–110 mg/dl), or the conventional approach which only recommended insulin therapy when blood glucose levels exceeded 12 mmol/l. Strict blood glucose control reduced the intensive care mortality of critically ill patients by more than 40%. Even patients in the conventional insulin treatment schedule with only moderate hyperglycemia (6.1–11.1 mmol/l), the equivalent of the therapeutic arm in the DIGAMI study, showed higher mortality compared to the patients in the strict glycemic control schedule [3]. Intensive insulin therapy also had a major effect on morbidity. It decreased the duration of ventilatory support and intensive care stay, Allison SP, Go VLW (eds): Metabolic Issues of Clinical Nutrition. Nestlé Nutrition Workshop Series Clinical & Performance Program, vol 9, pp 69–75, Nestec Ltd., Vevey/S. Karger AG, Basel, © 2004.