Background: Silent myocardial ischemia (SMI) is a frequent finding among diabetic patients. There are very few data on the relationship between homocysteine, which is a novel cardiovascular risk factor, and SMI in diabetic patients. We investigated whether plasma homocysteine has a predictive value for early diagnosis of SMI in type 2 diabetic patients. Methods: One hundred and twenty diabetic patients and 25 control subjects were evaluated. Among diabetic patients, 29 had a history or clinical signs of coronary artery disease (CAD). All other patients who had normal ECGs and no history or clinical signs of CAD were screened by exercise test. Thirty-eight patients with maximal negative exercise test were labelled as CAD (-) diabetic patient group. Angiography was performed on patients who had positive exercise tests and among them 23 patients had angiographically documented SMI. Results: CAD (+) and SMI groups had significantly higher serum homocysteine concentrations than CAD (-) and control groups (14.2+/-6.6, 15.7+/-7.8, 9.6+/-3.23, 9.3+/-2.25 mumol/l, respectively). In the SMI (+) diabetic group there was a significant correlation between serum homocysteine concentrations and creatinine, microalbuminuria and folic acid levels. Multiple regression analysis showed that homocysteine concentration was dependent on microalbuminuria, folic acid levels and presence or absence of ischemia. Conclusion: The present investigation shows an association of homocysteine with SMI in diabetic patients. Other prospective studies are needed to establish whether homocysteine levels can be used as a suitable marker for CAD screening in type 2 diabetic patients. (C) 2004 Elsevier Inc. All rights reserved.