What goes up should come down? Hyperglycaemia following stroke

More than a century after William Gowers first acknowledged the difficulties that exist in demonstrating the influence of treatment in acute stroke, there is still no safe, simple and effective medical therapy that can be administered to the majority of patients to limit neuronal damage and improve recovery. Recent advances in acute stroke treatment have been either consistently disappointing (neuroprotective therapy) or fraught with controversy regarding risk/benefit (thrombolysis) and attention is once again being directed towards physiological variables that may influence stroke outcome. In the absence of a proven medical therapy there is increasing evidence that the provision of specialist stroke care within acute and rehabilitation stroke units is associated with reductions in mortality, dependency and subsequent need for institutional care [1]. It was initially proposed that these benefits are the result of co-ordinated care, staff specialization and education, however most recent evidence from acute stroke unit studies suggests that factors such as early hydration and mobilization are also important in distinguishing specialist from conventional care [2]. In parallel to the evidence supporting stroke unit care there has been a plethora of clinical studies linking global and local metabolic factors to stroke outcome and it is only now that clinical trials are being conducted to explore these associations. One of the strongest and indeed first described associations between a physiological variable and stroke outcome exists for hyperglycaemia where there is increasing evidence from both animal and clinical studies that Diabetes Mellitus (DM) and/or hyperglycaemia is associated with an adverse prognosis. Hyperglycaemia is a frequent finding following acute stroke [3] and may reflect the metabolic stress of the acute event, so-called stress hyperglycaemia, and/or underlying impaired glucose metabolism (DM or Impaired Glucose Tolerance). Both insulin dependent and non-insulin dependent diabetes are major risk factors for stroke [4, 5]. Diabetes has also been shown to be associated with increased mortality and reduced functional outcome after stroke [5–7]. Several large clinical studies have now demonstrated a positive association between a raised blood glucose and poor outcome from stroke; greater mortality and reduced functional recovery [6, 8–10]. What is not entirely clear is to what extent hyperglycaemia is a ‘normal’ physiological response to stroke or whether hyperglycaemia per se increases cerebral damage in the acute phase. There are many potential mechanisms by which hyperglycaemia can exert a harmful effect upon cerebral tissue and it is probable that an important relationship exists, not only between glucose and stroke outcome, but also between insulin and neuroprotection [11]. It now remains to be determined whether lowering and maintaining ‘normal’ glucose levels in the immediate aftermath of stroke, combined with the administration of insulin as an acute treatment, can modify this outcome. The United Kingdom Glucose Insulin in Stroke Trial (GIST UK) is a multi-centre randomized controlled trial, which seeks to determine whether outcome from acute stroke can be favourably influenced by glucose/potassium/insulin (GKI) induced and maintained euglycaemia [12]. Treatment comprises intravenous GKI or normal saline therapy for 24 hours in acute stroke patients presenting with mild to moderate hyperglycaemia (admission plasma glucose 6.1– 17 mmol/l) within 24 hours of symptom onset. The objective of the GKI treatment is to maintain capillary blood glucose between 4–7 mmol/l for the duration of the infusion. The primary outcome measures for the study are all cause mortality and the proportion of patients with a poor outcome (modified Rankin score 4–6 including death) at 12 weeks between treatment groups. Age and Ageing 2002; 31-S3: 6–8 # 2002, British Geriatrics Society