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
SeminarStress hyperglycaemia
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
References (123)
- et al.
Evidence for strict inpatient blood glucose control: time to revise glycemic goals in hospitalized patients
Metabolism
(2008) - et al.
Clinical effects of hyperglycemia in the cardiac surgery population: the Portland diabetic project
Endocr Pract
(2006) - et al.
Influence of individual characteristics on outcome of glycemic control in intensive care unit patients with or without diabetes mellitus
Mayo Clin Proc
(2005) - et al.
Cytokine production and hospital mortality in patients with sepsis-induced stress hyperglycemia
J Infection
(2007) - et al.
Relation of chronic and acute glycemic control on mortality in acute myocardial infarction with diabetes mellitus
Am J Cardiol
(2005) - et al.
Admission glycaemia and outcome after acute coronary syndrome
Int J Cardiol
(2007) - et al.
Impact of admission hyperglycemia and diabetes mellitus on short- and long-term mortality after acute myocardial infarction in the coronary intervention era
Am J Cardiol
(2007) - et al.
Japanese Acute Coronary Syndrome Study Investigators: Acute hyperglycemia is associated with adverse outcome after acute myocardial infarction in the coronary intervention era
Am Heart J
(2005) - et al.
Transient hyperglycemia in ischemic stroke patients
J Neurol Sci
(2001) Glycemic control, diabetic status, and mortality in a heterogeneous population of critically ill patients before and during the era of intensive glycemic management: six and one-half years experience at a university-affiliated community hospital
Semin Thorac Cardiovasc Surg
(2006)
Admission hyperglycemia and other risk factors as predictors of hospital mortality in a medical ICU population
Chest
Stress hyperglycaemia and increased risk of death after myocardial infarction in patients with and without diabetes: a systematic overview
Lancet
Eliminating the diabetic disadvantage: the Portland Diabetic Project
Semin Thorac Cardiovasc Surg
Hyperglycemia predicts mortality after CABG: postoperative hyperglycemia predicts dramatic increases in mortality after coronary artery bypass graft surgery
J Diabetes Complications
Hyperglycemia in patients undergoing cerebral aneurysm surgery: its association with long-term gross neurologic and neuropsychological function
Mayo Clin Proc
Effect of perioperative insulin infusion on surgical morbidity and mortality: systematic review and meta-analysis of randomized trials
Mayo Clin Proc
Role of cortisol in the metabolic response to stress hormone infusion in the conscious dog
Metabolism
Insulin-mediated glucose uptake by individual tissues during sepsis
Metabolism
Severity of insulin resistance in critically ill medical patients
Metabolism
Hyperglycemia enhances coagulation and reduces neutrophil degranulation, whereas hyperinsulinemia inhibits fibrinolysis during human endotoxemia
Blood
Altered glucose transporter mRNA abundance in a rat model of endotoxic shock
Biochem Biophys Res Commun
Diabetes of injury: novel insights
Endocrinol Metab Clin North Am
Intermittent high glucose enhances ICAM-1, VCAM-1 and E-selectin expression in human umbilical vein endothelial cells in culture: the distinct role of protein kinase C and mitochondrial superoxide production
Atherosclerosis
Intensive insulin therapy in the critically ill patients
N Engl J Med
Intensive insulin therapy in the medical ICU
N Engl J Med
German Competence Network Sepsis (SepNet). Intensive insulin therapy and pentastarch resuscitation in severe sepsis
N Engl J Med
Impact of tight glucose control by intensive insulin therapy on ICU mortality and the rate of hypoglycaemia: final results of the Glucontrol study
Intensive Care Med
Strict glycaemic control in patients hospitalised in a mixed medical and surgical intensive care unit: a randomised clinical trial
Crit Care
Intensive versus conventional insulin therapy: a randomized controlled trial in medical and surgical critically ill patients
Crit Care Med
Benefits and risks of tight glucose control in critically ill adults: a meta-analysis
JAMA
Intensive versus conventional glucose control in critically ill patients
N Engl J Med
Management of diabetes and hyperglycemia in hospitals
Diabetes Care
National diabetes fact sheet: general information and national estimates on diabetes in the United States, 2005
Oral glucose tolerance test: a reliable tool for early detection of glucose abnormalities in patients with acute myocardial infarction in clinical practice
Diabetes Care
Is admission hyperglycaemia in non-diabetic patients with acute myocardial infarction a surrogate for previously undiagnosed abnormal glucose tolerance?
Eur Heart J
Glucose intolerance is common in Japanese patients with acute coronary syndrome who were not previously diagnosed with diabetes
Diabetes Care
The prevalence of abnormal glucose regulation in patients with coronary artery disease across Europe: the Euro Heart Survey on diabetes and the heart
Eur Heart J
Prevalence and prediction of unrecognised diabetes mellitus and impaired glucose tolerance following acute stroke
Age Ageing
Impaired glucose metabolism in patients with acute stroke and no previous diagnosis of diabetes mellitus
QJM
Utility of HbA(1c) levels for diabetes case finding in hospitalized patients with hyperglycemia
Diabetes Care
Prevalence of elevated hemoglobin A1c among patients admitted to the hospital without a diagnosis of diabetes
J Clin Endocrinol Metab
Hyperglycemia: An independent marker of in-hospital mortality in patients with undiagnosed diabetes
J Clin Endocrinol Metab
Intensive insulin therapy in mixed medical/surgical intensive care units: benefit versus harm
Diabetes
Blood glucose concentration and outcome of critical illness: the impact of diabetes
Crit Care Med
Impact of admission hyperglycemia on hospital mortality in various intensive care unit populations
Crit Care Med
Fasting glucose in acute myocardial infarction: incremental value for long-term mortality and relationship with left ventricular systolic function
Diabetes Care
Prognostic implication of hyperglycemia in myocardial infarction and primary angioplasty
Am J Med
Diabetes and stress hyperglycemia associated with myocardial infarctions at an urban municipal hospital: prevalence and effect on mortality
Cardiol Rev
Blood glucose in acute stroke, different therapeutic targets for diabetic and non-diabetic patients?
Acta Neurol Scand
Admission blood glucose and short term survival in primary intracerebral haemorrhage: a population based study
J Neurol Neurosurg Psychiatry
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