Elsevier

The Lancet

Volume 373, Issue 9677, 23–29 May 2009, Pages 1798-1807
The Lancet

Seminar
Stress hyperglycaemia

https://doi.org/10.1016/S0140-6736(09)60553-5Get rights and content

Summary

Results of randomised controlled trials of tight glycaemic control in hospital inpatients might vary with population and disease state. Individualised therapy for different hospital inpatient populations and identification of patients at risk of hyperglycaemia might be needed. One risk factor that has received much attention is the presence of pre-existing diabetes. So-called stress hyperglycaemia is usually defined as hyperglycaemia resolving spontaneously after dissipation of acute illness. The term generally refers to patients without known diabetes, although patients with diabetes might also develop stress hyperglycaemia—a fact overlooked in many studies comparing hospital inpatients with or without diabetes. Investigators of several studies have suggested that patients with stress hyperglycaemia are at higher risk of adverse consequences than are those with pre-existing diabetes. We describe classification of stress hyperglycaemia, mechanisms of harm, and management strategies.

Introduction

Transient hyperglycaemia during severe illness in adult patients without known diabetes was thought to be harmless or even advantageous. However, results of a large randomised controlled trial1 showed clear mortality benefits from intensive insulin therapy for patients in intensive care units (ICUs), irrespective of whether a previous diagnosis of diabetes had been made. Subsequent reports2, 3, 4, 5, 6, 7, 8 in mixed medical and surgical ICUs have tempered initial enthusiasm for strict glycaemic control, mainly because of an unacceptable risk of hypoglycaemia. Such findings have triggered appeals for focused efforts to identify patients who are at high risk of hyperglycaemia-mediated harm and likely to benefit from interventions.9

Investigators of several studies suggest that patients with stress hyperglycaemia and no previous diagnosis of diabetes face worse consequences at a given severity of hyperglycaemia than do those with pre-existing diabetes. We describe challenges in identification and diagnosis of such patients, analyse the evidence that lends support to the harms of stress hyperglycaemia, review the unique causal features and proposed mechanisms of harm of stress hyperglycaemia, suggest management strategies, and identify areas of future study. We intend not to diminish the importance of pre-existing diabetes or chronic glycaemic control, but to draw attention to the adverse consequences or concomitant effects of acute hyperglycaemia.

Section snippets

Diagnosis

Stress hyperglycaemia generally refers to transient hyperglycaemia during illness and is usually restricted to patients without previous evidence of diabetes. For the purpose of this Seminar, we will discuss physical—rather than psychological—stress. However, the identification of such patients is complex. No guidelines specifically define stress hyperglycaemia. In a technical review written by the Diabetes in Hospitals Writing Committee of the American Diabetes Association (ADA),10 patients

Poor outcomes related to stress hyperglycaemia

Researchers of intravenous insulin therapy have not specifically compared patients with and without stress hyperglycaemia in prospective controlled studies.1, 2, 3, 4, 5, 6 Other investigators20 exclude patients without known diabetes altogether. With the exception of a few randomised trials, most data are observational and drawn from ICUs or patients with acute myocardial or cerebrovascular events. One retrospective review21 of 1886 unselected hospital inpatients was stratified according to

Pathophysiology

In the hospital setting, a combination of factors affect the development of stress hyperglycaemia (figure 2). The mechanisms for this disorder probably vary with the patients' underlying glucose tolerance, type and severity of disease, and stage of illness. The cause of hyperglycaemia in type 2 diabetes is a combination of insulin resistance and β-cell secretory defects. However, the development of stress hyperglycaemia is caused by a highly complex interplay of counter-regulatory hormones such

Mechanism of adverse outcomes

The typical chronic complications of diabetes take several years to develop; therefore, the explanation for a rise in harm that is related to stress hyperglycaemia needs further consideration (figure 4). Stress hyperglycaemia is mediated by much greater inflammatory and neuroendocrine derangements than are expected in chronic hyperglycaemia associated with diabetes. Possibly, these derangements heighten susceptibility to benefits of interventions. For example, multiorgan failure is associated

Management

Current guidelines107, 108 do not recognise stress hyperglycaemia as being different from pre-existing diabetes, although such guidelines might specify separate targets for ICU and non-ICU patients. Other than the distinction between surgical and medical ICU patients, insufficient data are available to recommend risk stratification for assignment of glucose targets with respect to the cause or severity of hyperglycaemia. However, some investigators have noted that the concept of separate

Prevention and monitoring

In most patients, hospital-related hyperglycaemia is not generally predictable or preventable. However, early recognition and interception might prevent its persistence and exacerbation. In patients with diabetes, observational data suggest that long-term preadmission glycaemic control might affect the operative risk for both cardiovascular and non-cardiac complications.55, 121 Furthermore, preoperative glucotoxicity could affect the ease with which postoperative control is achieved. Although

Future direction and conclusion

Prospective studies with follow-up data comparing diabetes and stress hyperglycaemia are needed. HbA1c should be reported both to exclude undiagnosed probable diabetes and to infer whether patients with diabetes have stress-related exacerbation of hyperglycaemia. Patients with non-diabetic stress hyperglycaemia should be compared with a subgroup of patients with diabetes who have stress-related exacerbation of hyperglycaemia, and those with non-diabetic normoglycaemia should be compared with

Search strategy and selection criteria

We searched PubMed with the terms “stress hyperglycemia”, “diabetes”, “hyperglycemia” in conjunction with the key modifying terms “admission”, “hospital”, “inpatient”, “intensive care unit”, “critical care”, “acute myocardial infarction”, and “acute stroke”. We also searched the reference lists of reports identified with this strategy for relevant publications. We prioritised controlled trials or meta-analyses and observational studies from the past 5 years. We used only studies in

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