Hemorrhagic transformation of ischemic stroke in diabetics on sulfonylureas

Ann Neurol. 2012 Nov;72(5):799-806. doi: 10.1002/ana.23680.


Objective: Disability or death occurs more frequently in patients with hemorrhagic transformation (HT) after ischemic stroke. In rat models of stroke, sulfonylurea (SU) drugs such as glibenclamide (adopted US name, glyburide) confer protection against swelling and HT through actions on the novel SUR1-regulated NC(Ca-ATP) channel. Here, we sought to determine whether the use of SU drugs in patients with diabetes mellitus (DM) presenting with acute ischemic stroke might influence the incidence of HT.

Methods: We retrospectively analyzed data on 220 patients with DM who presented with acute ischemic stroke, 43 of whom were managed with and continued to receive SU drugs, and 177 of whom were managed without (controls).

Results: During a median length of stay in hospital of 11 days, 20 control patients (11%) experienced symptomatic HT (sHT), whereas no patient in the SU group experienced sHT (p = 0.016). No patient in the SU group died, compared to 18 (10%) in the control group (p = 0.027). Similarly favorable outcomes were observed after matching for baseline imbalances and excluding outliers. In support of the proposed mechanism, we present a case of sHT in which an analysis of brain tissues obtained intraoperatively showed prominent upregulation of SUR1, the target of SU drugs, in microvessels and neurons.

Interpretation: We conclude that, in diabetic patients with acute ischemic stroke, prior and continued use of SU drugs is associated with reduced sHT compared to those whose treatment regimen does not include SU drugs.

Publication types

  • Case Reports
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • ATP-Binding Cassette Transporters / metabolism
  • Aged
  • Brain Ischemia / complications
  • Cerebral Cortex / metabolism
  • Cerebral Cortex / pathology
  • Cerebral Hemorrhage / etiology*
  • Cerebral Hemorrhage / prevention & control*
  • Diabetes Mellitus, Type 2 / complications*
  • Diabetes Mellitus, Type 2 / drug therapy
  • Diabetes Mellitus, Type 2 / mortality
  • Female
  • Functional Laterality
  • Humans
  • Hypoglycemic Agents / therapeutic use*
  • Male
  • Middle Aged
  • Platelet Endothelial Cell Adhesion Molecule-1 / metabolism
  • Potassium Channels, Inwardly Rectifying / metabolism
  • Receptors, Drug / metabolism
  • Retrospective Studies
  • Risk Factors
  • Stroke / complications*
  • Stroke / etiology
  • Stroke / metabolism
  • Sulfonylurea Compounds / therapeutic use*
  • Sulfonylurea Receptors
  • Time Factors
  • Treatment Outcome
  • Up-Regulation / drug effects


  • ABCC8 protein, human
  • ATP-Binding Cassette Transporters
  • Abcc8 protein, rat
  • Hypoglycemic Agents
  • Platelet Endothelial Cell Adhesion Molecule-1
  • Potassium Channels, Inwardly Rectifying
  • Receptors, Drug
  • Sulfonylurea Compounds
  • Sulfonylurea Receptors