Glucose Metabolism and Insulin Therapy

Hyperglycemia and outcome in critical illness

The development of stress-induced hyperglycemia is associated with several clinically important problems in a wide array of patients with severe illness or injury. An increasing number of reports associate the upon-admission degree of hyperglycemia and the duration of hyperglycemia during critical illness with adverse outcome. In patients who have severe brain injury, hyperglycemia was associated with longer duration of hospital stay, a worse neurologic status, pupillary reaction, higher

Blood glucose control with intensive insulin therapy

A landmark prospective, randomized, controlled clinical trial of intensive insulin therapy in a large group of patients admitted to the intensive care unit after extensive or complicated surgery or trauma revealed major clinical benefits on morbidity and mortality [3]. In the conventional management of hyperglycemia, insulin was administered only when blood glucose levels exceeded 220 mg/dL, with the aim of keeping concentrations between 180 and 200 mg/dL, resulting in mean blood glucose levels

Insulin resistance and hyperglycemia

The stress imposed by any type of acute illness or injury leads to the development of insulin resistance, glucose intolerance, and hyperglycemia. Hepatic glucose production is upregulated in the acute phase of critical illness, despite high blood glucose levels and abundantly released insulin. Elevated levels of cytokines, growth hormone, glucagon, and cortisol might play a role in the increased gluconeogenesis [18], [19], [20], [21], [22]. Several effects of these hormones oppose the normal

Preventing glucose toxicity with intensive insulin therapy

It is striking that during the short period that patients need intensive care, avoiding even a moderate level of hyperglycemia with insulin improves the most feared complications of critical illness. In critically ill patients, hyperglycemia thus seems much more acutely toxic than in healthy individuals, for whom cells can protect themselves by downregulation of glucose transporters [33]. This acute toxicity of high levels of glucose in critical illness might be explained by an accelerated

Metabolic and non-metabolic effects of blood glucose control with intensive insulin therapy

Similar to the serum lipid profile of patients who have diabetes [46], the lipid metabolism in critically ill patients is strongly deranged. Most characteristically are elevated triglycerides together with low levels of HDL and LDL cholesterol [47], [48], [49]. Insulin therapy almost completely reversed this hypertriglyceridemia and substantially elevated HDL and LDL and the level of cholesterol associated with these lipoproteins [31]. Insulin treatment also decreased serum triglycerides and

Glucose control or insulin?

Multivariate logistic regression analysis of the results of the Leuven study indicated that blood glucose control and not the insulin dose administered statistically explains most of the beneficial effects of insulin therapy on outcome of critical illness [4]. It seemed crucial to reduce blood glucose levels to less than 110 mg/dL for the prevention of morbidity events such as bacteremia, anemia, and acute renal failure. The level of hyperglycemia was also an independent risk factor for the

Summary

Hyperglycemia in critically ill patients is a result of an altered glucose metabolism. Apart from the upregulated glucose production (gluconeogenesis and glycogenolysis), glucose uptake mechanisms also are affected during critical illness and contribute to the development of hyperglycemia. The higher levels of insulin, impaired peripheral glucose uptake and elevated hepatic glucose production reflect the development of insulin resistance during critical illness.

Hyperglycemia in critically ill