Hyperglycemia and Glycemic Control

Hyperglycemia — an elevated blood glucose concentration — is common in critically ill patients even without pre-existing diabetes, arising as part of the metabolic stress response to severe illness. Glycemic control refers to the use of insulin and monitoring to keep blood glucose within a target range, a practice whose optimal target has been reshaped by large randomised trials.

Definition

Hyperglycemia and glycemic control in critical illness refers to the elevation of blood glucose that accompanies severe illness — often termed stress hyperglycemia — and to the strategy of monitoring and treating it, principally with insulin, to maintain glucose within a chosen range.

Scope

This topic covers stress hyperglycemia and its mechanisms, the rationale for glycemic control, the contrasting findings of landmark trials of tight versus conventional control, and the place of hypoglycaemia as a competing harm. It is a reference-educational overview of the concept and the evidence; it does not specify glucose targets, insulin regimens, or individualised management.

Key concepts

• Stress hyperglycemia
• Insulin resistance of critical illness
• Tight versus conventional glucose control
• Iatrogenic hypoglycaemia
• Glycemic variability
• Target blood-glucose range

Mechanisms

Severe illness activates counter-regulatory hormones (cortisol, catecholamines, glucagon, growth hormone) and inflammatory mediators that increase hepatic glucose production and impair peripheral glucose uptake, producing insulin resistance and hyperglycemia even in patients without diabetes. This stress hyperglycemia is associated with worse outcomes, which provided the rationale for controlling glucose with insulin infusions. Lowering glucose too aggressively, however, introduces the competing risk of hypoglycaemia, which is itself harmful; alongside the absolute level, the variability of glucose over time has been identified as a further correlate of poor outcome.

Clinical relevance

Glucose management is a routine part of critical care, and the balance between controlling hyperglycemia and avoiding hypoglycaemia is informed directly by major trials, so understanding that evidence is part of critical care literacy. This entry describes the concept and the trial findings for reference and education; the specific glucose target and insulin strategy for an individual patient are clinical decisions outside its scope.

Epidemiology

Hyperglycemia is detected in a large proportion of intensive care unit patients, including many without known diabetes, and has been associated with increased mortality in observational data. The trials that followed established that very tight control increases hypoglycaemia and, in the largest trial, was associated with higher mortality than a more moderate target.

History

A single-centre trial by Van den Berghe (2001) reported that tight glucose control with intensive insulin therapy reduced mortality in surgical intensive care, prompting widespread adoption of tight targets. Subsequent multicentre trials could not reproduce the benefit, and the large NICE-SUGAR trial (2009) found that very tight control increased severe hypoglycaemia and was associated with higher mortality than conventional control. The field consequently moved away from very tight targets toward moderate glucose control, a shift reflected in later guidance.

Debates

What is the right blood-glucose target in critical illness?

After an early trial suggested benefit from tight control, the larger NICE-SUGAR trial found harm from very tight targets driven by hypoglycaemia, so the optimal target moved toward a moderate range; whether targets should be individualised (for example by diabetes status) continues to be debated.

Key figures

• Greet Van den Berghe
• Simon Finfer
• James Krinsley
• Jean-Charles Preiser

Seminal works

• vandenberghe-2001
• nice-sugar-2009

Frequently asked questions

Why do critically ill patients without diabetes develop high blood glucose?

Severe illness triggers a stress response — counter-regulatory hormones and inflammation — that raises glucose production and causes insulin resistance, producing hyperglycemia even in patients with no prior diabetes.

Why did very tight glucose control fall out of favour?

Although an early trial suggested benefit, the large NICE-SUGAR trial found that very tight control caused more severe hypoglycaemia and was associated with higher mortality than a more moderate target, shifting practice toward moderate control.