Glycemic Variability: Prognostic Impact on Acute Ischemic Stroke and the Impact of Corrective Treatment for Hyperglycemia. The GLIAS-III Translational Study

Introduction: Glycemic variability (GV) represents the amplitude of oscillations in glucose levels over time and is associated with higher mortality in critically ill patients. Our aim is to evaluate the impact of GV on acute ischemic stroke (IS) outcomes in humans and explore the impact of two different insulin administration routes on GV in an animal model.

Methods: This translational study consists of two studies conducted in parallel: The first study is an observational, multicenter, prospective clinical study in which 340 patients with acute IS will be subcutaneously implanted a sensor to continuously monitor blood glucose levels for 96 h. The second study is a basic experimental study using an animal model (rats) with permanent occlusion of the middle cerebral artery and induced hyperglycemia (through an intraperitoneal injection of nicotinamide and streptozotocin). The animal study will include the following 6 groups (10 animals per group): sham; hyperglycemia without IS; IS without hyperglycemia; IS and hyperglycemia without treatment; IS and hyperglycemia and intravenous insulin; and IS and hyperglycemia and subcutaneous insulin. The endpoint for the first study is mortality at 3 months, while the endpoints for the animal model study are GV, functional recovery and biomarkers.

Discussion: The GLIAS-III study will be the first translational approach analyzing the prognostic influence of GV, evaluated by the use of subcutaneous glucose monitors, in acute stroke. Trial registration https://www.clinicaltrials.gov (NCT04001049).

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