After Stroke

A retrospective study by Melamed (7, 15) showed in 1976 that hyper-glycemia after stroke is frequent and relates to the severity of the stroke and in-hospital mortality. Since then many studies have reported similar associations and showed that this association is more pronounced if hyperglycemia persists during the first 24 h (18) or week (50, 51).

Capes et al. performed a systematic review including a total of 33 studies and demonstrated that after stroke of either subtype (ischemic or hemor-rhagic), the unadjusted relative risk of short-term mortality associated with admission glucose levels greater than 6-8 mmol/L was 3.1 [95% confidence interval (95%CI), 2.5-3.8] in non-diabetic patients and 1.3 (95%CI, 0.5-3.4) in diabetic patients (8). For non-diabetic patients, glucose levels greater than 6.1-7.0 mmol/L were associated with a 3.3-fold higher risk of short-term mortality in patients with ischemic stroke - but not in non-diabetic patients with hemorrhagic stroke (2.4; 95%CI, 0.9-8.7) (Fig. 2). Recently, this observation was confirmed in a post hoc analysis of a large clinical stroke trial (18). The review by Capes et al. showed also that after hemorrhagic stroke,

Fig. 2. Unadjusted relative risk (RR) of in-hospital or 30-day mortality after stroke in patients with stress hyperglycemia compared with those without stress hyperglycemia. In patients without known diabetes the pooled relative risk for ischemic stroke is 3.3 (95% confidence intervals (CI): 2.3-4.6) for hemorrhagic stroke: 2.4 (95%CI: 0.7-8.73). (From Capes et al. (8). Reprinted with permission from Lippincott Williams & Wilkins.)

Fig. 2. Unadjusted relative risk (RR) of in-hospital or 30-day mortality after stroke in patients with stress hyperglycemia compared with those without stress hyperglycemia. In patients without known diabetes the pooled relative risk for ischemic stroke is 3.3 (95% confidence intervals (CI): 2.3-4.6) for hemorrhagic stroke: 2.4 (95%CI: 0.7-8.73). (From Capes et al. (8). Reprinted with permission from Lippincott Williams & Wilkins.)

admission hyperglycemia was not associated with higher short-term mortality in either diabetic or non-diabetic patients. Some of these data have to be interpreted with caution, however, because insufficient data could account for the lack of a significant correlation in the subgroup analyses. For example, more recent studies have convincingly demonstrated that admission hyperglycemia independently predicts poor outcome, also after hemorrhagic stroke (10-12).

The review by Capes et al. did not perform a subgroup analysis for patients with lacunar or non-lacunar stroke. Interestingly, in a small retrospective analysis that we performed (52) and in the post hoc analysis of three large clinical trials the association between hyperglycemia and poor outcome was confirmed, but only for patients with cortical stroke. In contrast, for patients with lacunar stroke hyperglycemia appears to be associated with improved, rather than poor outcome (16, 53). Many studies that related hyperglycemia to outcome have been performed before thrombolytic therapy with recombinant tissue plasminogen activator (rt-PA) became standard practice. Meanwhile, an increasing number of studies have demonstrated that hyperglycemia on admission also predicts poor outcome in patients treated with rt-PA. This association is even stronger than for non-rt-PA-treated patients (12-14, 54, 55). This has led to the suggestion that hyper-glycemia may in part counterbalance the beneficial effect of rt-PA treatment (54).

In conclusion, admission hyperglycemia after stroke, either ischemic or hemorrhagic, is associated with poor outcome and this association is more pronounced (i) if hyperglycemia persists after the acute phase; (ii) in patients with cortical stroke; (iii) in patients without a history of DM, and (iv) in patients receiving rt-PA treatment. In contrast, after lacunar stroke high levels of blood glucose may predict improved outcome. These observations emphasize that stroke is a heterogeneous disorder and not a single entity and stress the need to study hyperglycemia after stroke for each stroke subtype separately.

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