World Health Organization criteria for the diagnosis of hyperglycemic states cannot be applied under conditions of acute circulatory or other stress [1]. Conventionally the OGTT can not be properly interpreted until 3 months after myocardial infarction. This concept should now be revised in the light of finding that the rates of new diabetes and IGT within the coronary care unit are almost identical to those 3 months later (even though the absolute correlation of the 2-h plasma glucose levels is modest, r = 0.49). The study highlights the inadequacy of fasting blood glucose levels alone to reveal IGT and new diabetes mellitus.
Our perceptions of ‘stress hyperglycemia’ must change. There is very strong evidence from a meta-analysis of 15 descriptive studies [2] that after myocardial infarction non-diabetic hyperglycemia is associated with an increased risk of in-hospital mortality. Patients with glucose concentrations in the range 6.1–8.0 mmol/l (110–144 mg/100 ml) have a 3.9-fold (95% CI 2.9–5.4) higher risk of death. With glucose concentrations at or above 10.0–11.0 mmol/l (180–200 mg/100 ml) the risk of death was only moderately increased (relative risk 1.7, 95% CI 1.2–2.4). It is possible that the use of insulin in the latter improved their outcome.
Is non-diabetic hyperglycemia in the coronary care setting a modifiable risk factor? The answer is almost certainly yes. The one intervention trial in diabetic patients with AMI (the DIGAMI Study [3]) showed that the 3-year prognosis was improved by strict metabolic care involving acute insulin-glucose infusion and long-term subcutaneous insulin. The greatest benefit was seen in those patients who had had no prior insulin and who were at comparatively low cardiovascular risk, in whom there was an absolute mortality risk reduction from 33% in the control group and 15% in the intensively treated group (a relative risk reduction of 51%). We need confirmation of the DIGAMI results in further studies sufficiently powered to identify the separate benefits of acute and long-term insulin therapy.
Similar benefits were described in critically ill patients requiring mechanical ventilation in a surgical intensive care unit [4]. A low threshold of blood glucose ³6.1 mmol/l (110 mg/100 ml) for commencement of insulin therapy was used, and the strict target for normoglycemia was a blood glucose level of 4.5–6.0 mmol/l (80–110 mg/ml). There was a substantial reduction in mortality within the intensive care unit from 8.0% to 4.6% (a relative risk reduction of 43%), together with a reduction of overall in-hospital mortality of 34%. Only 13% of the patients were diabetic. The study emphasizes the importance of vigorous treatment of non-diabetic hyperglycemia in critically ill patients.
In AMI, hyperglycemia is mediated by increased catecholamine, cortisol and growth hormone secretion. Insulin therapy reduces the subsequent release of free fatty acids and their toxicity, promotes myocardial uptake of glucose for anaerobic metabolism, reduces arrhythmias and reverses the procoagulant effects of insulin resistance.
The outcomes of well-planned clinical trials are urgently awaited. Meanwhile endocrinologists should establish a dialogue with their cardiologist colleagues to agree on ‘best practice’ guidelines for the management of hyperglycemia identified in the coronary care unit. While implementation of intensive intravenous insulin therapy after AMI is feasible, the education and aftercare of patients found to have abnormal glucose tolerance will require increased hospital and community resources.

References
1. World Health Organization. Definition, diagnosis and classification of diabetes mellitus and its complications. Report from a WHO consultation. Part 1: diagnosis and classification of diabetes mellitus. WHO/NCD/NCS/99.2. Geneva: World Health Organization, 1999.
2. Capes SE, Hunt D, Malmberg K, Gerstein HC. Stress hyperglycaemia and increased risk of death after myocardial infarction in patients with and without diabetes: a systematic overview. Lancet 2000; 355: 773–8.
3. Malmberg K, Norhammar A, Wedel H, Rydén L. Glycometabolic state at admission: important risk marker of mortality in conventionally treated patients with diabetes mellitus and acute myocardial infarction. Circulation 1999; 99: 2626–32.
4. Van Den Berghe G, Wouters P, Weekers F et al. Intensive insulin therapy in critically ill patients. N Engl J Med 2001; 345: 1359–67.

Summary and Comment:
Timothy Welborn, Nedlands, Australia