Insulin Resistance Intervention After Stroke Trial

Inclusion Criteria

1. Ages 40 years or greater at the time of randomization.
2. Ischemic stroke or TIA no less than 14 days and no more than 6 months before randomization
3. Documentation of insulin resistance as defined by a value over 3.0 on the Homeostasis Model Assessment of insulin sensitivity (HOMA).
4. Both ability and willingness to provide informed consent.
5. Presence of none of the exclusion criteria.

Exclusion Criteria

Permanent Exclusions

1. Severely disabling stroke as indicated by an inability to participate in scheduled follow-up activities.
2. Persons whose ischemic stroke or TIA was related to structural cardiac lesion, significant head trauma, proximal arterial dissection or medical instrumentation.
3. Diabetes mellitus as defined by recent use of medication for diabetes as an out-patient (\*see note below) or two fasting plasma blood sugars \> 126 mg/dL.
4. HgbA1c \> 7.0%.
5. Irreversible medical conditions likely to affect short-term survival or ability to participate in the study protocol. These include:

* Cancer or other chronic disease with poor prognosis (predicted survival of less than four years).
* Severe neurologic or psychiatric disease that would complicate the evaluation of study outcomes (e.g., dementia or schizophrenia).
6. History of intolerance to any thiazolidinedione.
7. Pregnancy or desire to become pregnant.
8. Oral contraceptive use.
9. Ongoing use of oral corticosteroids.
10. History of heart failure
11. Active liver disease as defined by known liver disease accompanied by cirrhosis, significant cholestasis, portal hypertension, hepatic encephalopathy, hepatic synthetic dysfunction, or expected significant loss of liver function over the course of the study.
12. History of bladder cancer.
13. Current participation in a conflicting clinical trial. A conflicting clinical trial is defined as a trial with any of following:

* Intervention that is known to affect the incidence of stroke or myocardial infarction.
* Intervention that is an experimental drug.
* Outcome that includes stroke or myocardial infarction.
* Exclusion for participation in another trial.

Temporary Exclusions Persons with temporary exclusions may be enrolled as soon as the exclusion has resolved.

1. Alanine aminotransferase (ALT) \>2.5 times the upper limit of normal.
2. Hemoglobin \<8.5 g/dl.
3. Moderate or severe pitting edema of the feet or legs (IRIS grade 3 or 4).
4. Carotid surgery or carotid stenting procedure scheduled (delay randomization until 2 weeks following procedure).