Plasma phospholipid transfer protein (PLTP) mediates both net transfer and exchange of phospholipids between different lipoproteins. Animal studies have shown that it is closely related to the development of atherosclerosis. Although many studies have indicated that PLTP activity is increased in diabetes mellitus, the role of PLTP in diabetes is still unclear. To evaluate the influence of a high-fat meal on PLTP activity, 50 nondiabetic patients with coronary heart disease (CHD), 50 insulin-treated Type 2 diabetics, and 50 healthy controls were included. We determined PLTP activity before and 4 and 8 h after a high-fat meal. As expected, serum PLTP activity was significantly higher in CHD patients than in healthy controls (71.0 +/- 46.2 vs. 54.0 +/- 33.8 pmol/microl/h, P = 0.032) at baseline. More importantly, we found that serum PLTP activity increased to its maximum 4 h after fat loading and then decreased to nearly basal levels after 8 h both in controls and CHD patients. In contrast, PLTP activity continuously increased during this time period in the diabetic patients. With regards to the data from this study we hypothesize that serum PLTP is involved in the clearance of postprandial lipoproteins and this process is attenuated in diabetes. Since postprandial lipoproteins are atherogenic, the delay in clearance of these particles could play an important role in the development of atherosclerosis in patients with diabetes mellitus.