Alejandro Rodríguez-Vázquez, MD
Blood glucose level is classically one of the most important modifiers in acute ischemic stroke prognosis. Hyperglycemia is common in the acute setting of stroke, even in non-diabetic patients, and is related to lower recanalization rates and poor prognosis through several mechanisms like glucose-induced intracellular acidosis, or the formation of reactive oxygen and nitrogen species that lead to mitochondrial dysfunction, edema and reperfusion injury.
In this study, the authors analyzed blood glucose levels at admission of 2908 patients with large vessel occlusion (LVO) of the anterior circulation who underwent endovascular treatment (EVT) between March 2014 and November 2017. This data was obtained prospectively from the Dutch nationwide MR CLEAN registry. Hyperglycemia was defined as the first glucose on admission over 7.8 mmol/L in accordance with previous studies and the American Diabetes Association criteria. The main outcome was functional status at 90 days assessed with the modified Rankin scale (mRS). Secondary outcomes included poor clinical situation (mRS 3-6) and mortality at 90 days, symptomatic intracranial hemorrhage (sICH) defined as an NIHSS increase of 4 or more points and other complications like recurrent stroke, stroke progression, pneumonia and other infections.
Of the 2908 registered patients, 882 (30%) had hyperglycemia at admission. Patients with hyperglycemia were slightly older (median age in years 73 vs 71, P<0.001), more often female (53% vs 49%, P=0.021), and higher frequency of history of diabetes (36% vs 7%, P<0.001) and hypertension (62% vs 49%, P<0.001). Additionally, they had higher median NIHSS basal scores (16 vs 15, P<0.001), longer onset-to-groin times (205 vs 191 minutes, P<0.001) and worse collateral scores.
After adjustment, hyperglycemic patients had a worse functional outcome at 90 days (mRS 4 vs 3, P<0.001). Of all these patients, only 30% had a good functional outcome of mRS score 0-2 compared to 46% of non-hyperglycemic patients. Mortality rates were also higher (40% vs 23%, aOR 1.95 [95% CI, 1.60–2.38]), as well as sICH (9% vs 5%; aOR, 1.94 [95% CI, 1.41–2.66]), stroke progression (12% versus 8%; aOR, 1.44 [95% CI, 1.10–1.89]), pneumonia (15% vs 10%; aOR, 1.48 [95% CI, 1.16–1.88]), and other infections (5% vs 3%; aOR, 1.50 [95% CI, 1.03–2.19]). There were no differences in the rates of successful reperfusion or other complications. Analyzing glucose as a continuous variable, it was nonlinearly associated with 90-day mortality, probability of symptomatic intracranial hemorrhage (Figure 1) and a poor functional outcome, the latter showed a J-shaped curve with a nadir at 6 mmol/L (Figure 2).
Although this study includes a large sample size that reflects daily clinical practice, its main limitation is its nature as an observational registry and thus it is not randomized. Furthermore, it did not include follow-up glucose level data, so it is not possible to determine if sustained hyperglycemia plays a larger role regarding outcome. However, it strongly highlights the importance of blood glucose levels in the acute setting of an ischemic stroke, identifying it as a potential target for adjuvant treatment to reperfusion therapies. In 2019, the SHINE (Stroke Hyperglycemia Insuline Network Effort) clinical trial showed no benefit of intensive glucose control regarding outcome at 90 days in an heterogenous stroke population. However, randomized controlled trials should be designed to determine if patients specifically treated with EVT might benefit from early glucose-lowering therapy and, in this case, help to establish the optimal thresholds. In addition, novel technologies like continuous glycemia measured via subcutaneous-implanted devices could be useful to optimize the medical care in stroke units, allowing us to give the best treatment after a successful (or not successful) EVT.
