Diabetes Mellitus: A Common Comorbidity Increasing Hemorrhagic Transformation after tPA Thrombolytic Therapy for Ischemic Stroke

Abstract Intravenous tissue type plasminogen activator thrombolytic therapy (IV tPA) has long been a mainstay in acute ischemic stroke (AIS) therapy. However, patients receiving IV tPA therapy may have variable response with some subsets of patients having worsened outcomes. Diabetes mellitus (DM), a clinically important and common vascular co-morbidity in AIS patients, can result in increased risk of hemorrhagic transformation (HT) after IV tPA therapy. In this short-review, we summarize the recent advances in understanding the mechanisms underlying the exacerbated HT after IV tPA therapy in AIS patients with DM. Potential precipitating factors including more severe blood-brain barrier disruption, enhanced oxidative stress, neuroinflammation and apoptosis, as well as several others contributors such as abnormal protein glycation, extracellular proteolytic dysfunction and impairment of collateral flow in DM are discussed. Additionally, several tPA combination approaches from experimental studies that may help to ameliorate the aggravation of post IV tPA-induced HT in AIS patients with DM are also briefly summarized. Urgently, more clinical and experimental studies aiming to better understand the mechanisms involved in DM-related exacerbation of HT after IV tPA therapy in AIS are needed for developing potential approaches protecting against this harmful complication in AIS patients with DM.