Carbohydrate and insulin activity in critically ill patients

The term “diabetes of stress” has been used for more than 50 years to describe the general clinical condition of hyperglycemia with the simultaneous elevation of insulin concentration, particularly during food intake. An elevated rate of glucose production is central to the disruption of normal glucoregulation in critical illness [1]. Since gluconeogenesis in critical illness is not responsive to the normally suppressive effect of insulin, the liver is a major site of the insulin resistance. Nonetheless, the concept of “diabetes of stress” has classically referred to the resistance to the peripheral action of insulin to stimulate glucose uptake, which is a general characteristic of diabetes. However, in contrast to the apparently-analogous situation of diabetes, the basal rate of peripheral glucose clearance is generally elevated in critical illness [1,2]. This observation is consistent with the general notion of peripheral “insulin resistance” in critical illness because most of glucose uptake in the basal state occurs in insulin-independent tissues [brain, erythrocytes, wound tissue). In fact, within the physiological range of insulin concentration, the hypoglycemic action of insulin has diminished in critically ill patients [2, 3]. On the other hand, the maximal physiological effectiveness of insulin is not markedly reduced in severe injury [2], particularly if the effect of bedrest in the injured patient is considered [4]. In contrast, in sepsis the maximal effectiveness of insulin has decreased approximately 50% below normal [2]. The mechanism explaining the difference in magnitude of insulin resistance between sepsis and severe injury is not clear. The resistance to a physiological increase in insulin concentration has been demonstrated in a variety of experiments in injured patients. For example, when glucose was infused into severely burned patients and normal volunteers at a constant rate (4 mg/kg·min), almost five times as much insulin had to be infused into the patients as into normal volunteers in order to maintain the basal glucose concentration [1].