Strokeand Hyperglycemia

Hyperglycemia is a frequent finding in various medical emergencies, and it has clearly been associated with poor outcome. Hyperglycemia is potentially modifiable, and in the past decade a number of trials have been published that investigated the potential beneficial effect of tight glycemic control on outcome in various acute diseases such as myocardial infarction or in patients admitted to an intensive care unit (ICU) (2,3). Asa result, tight glycemic control has now worldwide become standard practice in the ICU. For several other patient groups treatment protocols have been adjusted to a more strict regulation of blood glucose levels.

Also after stroke, hyperglycemia is frequent and is independently associated with poor outcome. Although this is already known for a few decades, the 1994 guidelines for the treatment of ischemic stroke from the American Heart Association (AHA) did not make any recommendation for the treatment of hyperglycemia in these patients. More recent (2007) consensus papers recommended treating glucose levels more strictly, despite the lack of apparent evidence of a clinical benefit (4-6).

In this chapter, focusing on ischemic stroke, we will first outline the incidence and the natural course of post-stroke hyperglycemia, next we will discuss the etiology of post-stroke hyperglycemia and the various mechanisms that could explain how acute hyperglycemia can be detrimental after ischemic stroke. Finally, we will address the question if in-hospital hyper-glycemia should be treated, what such treatment should aim for, and the difficulties that arise when treating hyperglycemia in ischemic stroke patients.

HYPERGLYCEMIA AFTER STROKE Incidence of Admission Hyperglycemia After Acute Stroke

In acute stroke, hyperglycemia on admission has been recognized for a long time, also in patients without pre-existing diabetes mellitus (DM) (7). Despite considerable differences between studies concerning stroke subtypes, cut-off values used to define hyperglycemia (6-10mmol/L), the condition under which glucose was assessed (random vs. fasting; capillary vs. plasma), and time between the ictus and glucose assessment, the rate of admission hyperglycemia is consistently high. In a systematic review the included studies reported that 8-63% of non-diabetic and 39-89% of diabetic stroke patients had hyperglycemia on admission (8).

Only few studies investigated admission glucose levels in different stroke types. Studies that assessed glucose levels separately for ischemic or hem-orrhagic stroke, however, report similar glucose levels, ranging between 7 and 8 mmol/L (9-14). One study that specifically looked at clinical subtypes of ischemic stroke reports that hyperglycemia exists across all ischemic stroke subtypes, but is higher after cortical stroke (15). This observation is supported by post hoc analyses of two large clinical trials including 1,375 patients within 6 h from stroke onset. In this report, glucose levels were also slightly higher in patients with cortical, compared to patients with subcortical infarctions (7.9 vs. 7.6 mmol/L) (16).

Natural Course of Hyperglycemia Post-stroke

Although hyperglycemia on admission has been reported frequently, few studies have described the natural history of glucose levels during the clinical course of stroke. In a large clinical trial investigating the effect of tight glycemic control on outcome, glucose levels in the hyperglycemic control group declined spontaneously within the first 24 h (17), and recently the post hoc analysis of another large clinical trial measuring blood glucose at 6 and 24 h post-ischemic stroke reports the same pattern (18). Unfortunately neither of these trials report blood glucose levels beyond this time frame. In a prospective study that used a continuous glucose monitoring device, patients were monitored for 72 h after admission. It was also shown that both in non-diabetic as well as in diabetic stroke patients' glucose levels initially decrease, but after 24-88 h, glucose levels rose again (19). This late (>24 h) hyperglycemic phase is probably the result of an underlying impairment of glucose metabolism once the patient resumes feeding after an initial fasting period (20, 21).

In conclusion, admission hyperglycemia is a frequent finding after stroke, also in the absence of DM and it occurs irrespective of stroke (sub)type, although glucose levels seem to be somewhat higher in patients with cortical as compared to subcortical infarctions. Glucose levels decrease spontaneously during the first 24 h, but once patients resume feeding, glucose levels surge again, possibly indicating an underlying, previously subclinical, impairment of glucose metabolism.

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