The glucose paradox of cerebral ischaemia.

 Copyright 2003 Journal of Postgraduate Medicine. Online full text at http://www.jpgmonline.com The issue of hyperglycaemia in patients with acute stress continues to generate a lot of debate. Up to 50% of patients with stroke are reported to have hyperglycaemia at admission to the hospital and up to 25% of those admitted to the hospital with stroke may report history of diabetes mellitus. This increased incidence of hyperglycaemia in patients with stroke could partly be explained on the basis of increased prevalence of diabetes mellitus in the society. It is also well known that blood glucose levels are increased in the first 12 hours after the onset of acute stroke (as in any other stressful situation including myocardial infarction). This magnitude of the rise in blood glucose level is supposedly related to the severity of the stroke. This could be another reason for hyperglycaemia noticed in patients with stroke. Although there is no unanimity amongst researchers, several studies, both animal and human, report that hyperglycaemia occurring at the onset of stroke is associated with a worse prognosis, irrespective of patient’s age, severity of the condition, or stroke sub-type. It exacerbates the ischaemic lesions and is associated with an increase in the brain oedema and augmentation in the size of the infarct. It is also associated with a decrease in cerebral blood flow. Positive association has been shown between the blood glucose level at admission and stroke volume with higher glucose levels associated with larger stroke volumes. Patients with transient hyperglycaemia have been reported to have larger ischaemic lesions on computerized tomographic scans and a higher 30-day mortality than that in normoglycaemic individuals. The worse outcome manifests itself in terms of longer hospital stay, higher inpatient hospital charges and increased short-term and long-term mortality. Researchers have invoked several mechanisms to explain the phenomenon of worsening of prognosis with hyperglycaemia. They point out that hyperglycaemia whether resulting form acute stress, poor glycaemic control in diabetic patients or both, worsens the prognosis through augmentation of acute brain injury and precipitation of intra-cerebral haemorrhage (ICH). Possible mechanisms responsible for augmenting acute ischaemic brain injury include increased brain tissue acidosis, accumulation of extra-cellular glutamate, increased blood–brain barrier permeability, cerebral oedema formation, decreased vascular reactivity or a combination of these. Hyperglycaemia-related increase in the size of infarction in animal studies has been blamed on impairment of mitochondrial function and facilitation of acidosis. Hyperglycaemia with reperfusion may augment ischaemic tissue acidosis, but it may The Glucose Paradox of Cerebral Ischaemia