Hyperglycemia Worsens Outcome After rt-PA Primarily in the Large-Vessel Occlusive Stroke Subtype

Abstract

Hyperglycemia at the time of ischemic stroke has been associated with poorer outcomes. Preclinical literature suggests that hyperglycemia is an independent prognostic factor and the vasculature is more vulnerable to reperfusion injury. We applied a method to match subjects on important baseline factors to test whether, independent of stroke severity, stroke subtype influences the effect of hyperglycemia on outcome after recombinant tissue plasminogen activator (rt-PA). We reanalyzed the NINDS rt-PA dataset with respect to matching variables baseline NIHSS, age, and investigator-determined stroke subtypes small-vessel occlusive stroke (SVS), large-vessel occlusive stroke (LVS), and cardioembolic stroke (CES), above and below a glucose threshold of 150 mg/dl. Ninety-day outcomes were compared. Post hoc baseline matching was excellent in most cases. Hyperglycemia was associated with worsened functional outcome mostly in the LVS subtype with increased mortality in the placebo arm (15.3% mortality normoglycemia vs. 30.6% hyperglycemia; p = .046), worse functional outcome in the rt-PA arm (modified Rankin Score (mRS) 0-1; 46.3 vs. 22.0%; p = .034), and no improvement in functional outcome with rt-PA compared to placebo (mRS 0-1; 25% in both groups). Among hyperglycemic subjects, CES subjects showed significant improvement following rt-PA (p = .027). After matching for baseline severity, the influence of hyperglycemia on outcome was primarily in the LVS subtype, especially after rt-PA. This finding is consistent with a deleterious effect of hyperglycemia on ischemia/reperfusion of symptomatic large arteries. If confirmed, the particular vulnerability of the LVS subtype is important in understanding the role of stroke subtype in the mechanism of worsening and potential treatment of hyperglycemic stroke patients.

Prevalence of diabetes and its effects on stroke outcomes: A meta‐analysis and literature review

“…In a majority of the studies included in the present review, an admission random glucose or a FBG was carried out and included in the analysis of the outcomes. Stress hyperglycemia has been associated with poorer functional outcomes 15,17,40,70 and mortality 71 , irrespective of diabetes status after an acute ischemic stroke. However, more studies have found that stress hyperglycemia has been associated with infarct volume growth, early neurological deterioration (increase of ≥4 points on National Institute of Health Stroke Scale) 16 , poorer functional outcome 12,40,41,71,72 , higher mortality 32,43,46,53,73 and longer hospital stay 40 in people without a history of diabetes, including patients who underwent thrombolysis 71,[74][75][76] and mechanical thrombectomy 77 .…”

Influence of Admission Blood Glucose in Predicting Outcome in Patients With Spontaneous Intracerebral Hematoma

“…Diabetes and high blood glucose are well-known risk factors for ischemic stroke (5, 27–29). While a number of ischemic studies showed worse outcomes with hyperglycaemia (7) others have shown protective effect of hyperglycaemia in small vessel disease (30).…”

Embracing Biological and Methodological Variance in a New Approach to Pre-Clinical Stroke Testing

“…There are additional contributions from the patient’s age [24, 25] and whether the patient underwent recanalization therapy [1]. Baseline glucose is also highly associated with outcome, particularly when the patient has undergone recanalization [26], consistent between human and animal models [27]. Collaterals, some genetically determined, are also known to play a role in stroke outcomes in both humans and animals and can be altered by acquired conditions such as cardiovascular risk factors [28–32].…”