Plasma lipid abnormalities associated with diabetes are thought to contribute to atherogenesis and overall cardiovascular morbidity. Fatty Acid Synthase (FAS), an essential multiunit enzyme that catalyzes the synthesis of long-chain fatty acids from acetyl-CoA and malonyl-CoA, was recently found to circulate in the plasma (pFAS). Since FAS is essential for the lipogenic functions of the liver and adipose tissue, and its tissue expression is altered in the setting of diabetes, we sought to evaluate whether pFAS is a biomarker for arterial occlusive disease in diabetic patients. To test this hypothesis, we compared the activity of pFAS in the fasting serum in a relatively homogenous group of 15 diabetic (DM) and 15 non-diabetic (NDM) patients who are undergoing carotid endarterectomy (CEA). We also evaluated pFAS in 15 additional control patients who have no evidence of arterial occlusive disease. Among selected patients, DM patients were more likely to have hypertension and receive metformin compared to NDM patients (P<0.05). Control patients who have no evidence of arterial occlusive disease were all <60 years old, and none had cardiovascular morbidities. DM patients undergoing CEA demonstrated a 39% increase in pFAS activity compared to NDM patients undergoing CEA (P=0.04), and a 91% increase compared to control patients (P<0.001). Similarly, on Western blot analysis DM patients demonstrated an average 27% increase compared to control patients (P=0.4). pFAS did not correlate with fasting plasma glucose, LDL, HDL, or total cholesterol, but demonstrated a modest correlation with fasting plasma triglycerides (R
2
=0.4, P=0.03). These findings suggest pFAS activity is altered in DM patients with carotid artery stenosis, and correlates with specific plasma lipid profiles suggestive of overall cardiovascular morbidity.