Plasma apolipoprotein E concentration is an important determinant of phospholipid transfer protein activity in type 2 diabetes mellitus

Abstract

Background: Phospholipid transfer protein (PLTP) transfers phospholipids between lipoproteins and plays an important role in HDL metabolism. PLTP exists as a high-activity and a low-activity form in the circulation. In vitro studies have shown that apolipoprotein (apo) E is involved in maintaining PLTP in the active form, while the low-activity form is associated with apo AI. We have therefore investigated whether plasma apo AI, B and E concentrations are important determinants of plasma PLTP activity in type 2 diabetes, a condition associated with increased plasma PLTP activity. Methods: Plasma PLTP activity was assayed by measuring the transfer of radiolabelled phosphatidylcholine from liposomes to HDL; apo AI and B by rate nephelometry and apo E by a 2-point turbidimetric assay. Results: Type 2 diabetic patients (n = 230) had higher PLTP activity than controls (n = 97) (2374 ± 628 nmol/mL/h versus 1862 ± 585 respectively, p < 0.01). They also had increased fasting triglyceride and low HDL. Plasma apo B (p < 0.01) and apo E (p < 0.05) were increased, whereas apo AI was reduced (p < 0.01). Univariate analysis showed that plasma PLTP activity correlated mainly with apolipoproteins AI and E. Stepwise regression analysis showed that apo E was the main determinant of plasma PLTP activity, accounting for 23% of its variability in the diabetic subjects and 8% in the controls respectively. Conclusions: The associations between plasma apo AI and E concentrations and PLTP activity suggest that these apolipoproteins are important regulators of PLTP activity in vivo. The increase in PUP activity in type 2 diabetes is partly related to the changes in these apolipoproteins. Copyright © 2006 John Wiley & Sons, Ltd.