Diabetes, stroke, and neuroresilience: looking beyond hyperglycemia.

Ischemic stroke is a leading cause of morbidity and mortality among type 2 diabetic patients. Preclinical and translational studies have identified critical pathophysiological mediators of stroke risk, recurrence, and poor outcome in diabetic patients, including endothelial dysfunction and inflammation. Most clinical trials of diabetes and stroke have focused on treating hyperglycemia alone. Pioglitazone has shown promise in secondary stroke prevention for insulin-resistant patients; however, its use is not yet widespread. Additional research into clinical therapies directed at diabetic pathophysiological processes to prevent stroke and improve outcome for diabetic stroke survivors is necessary. Resilience is the process of active adaptation to a stressor. In patients with diabetes, stroke recovery is impaired by insulin resistance, endothelial dysfunction, and inflammation, which impair key neuroresilience pathways maintaining cerebrovascular integrity, resolving poststroke inflammation, stimulating neural plasticity, and preventing neurodegeneration. Our review summarizes the underpinnings of stroke risk in diabetes, the clinical consequences of stroke in diabetic patients, and proposes hypotheses and new avenues of research for therapeutics to stimulate neuroresilience pathways and improve stroke outcome in diabetic patients.