Relationship of Phospholipid Transfer Protein Activity to HDL and Apolipoprotein B-Containing Lipoproteins in Subjects With and Without Type 1 Diabetes

Relationship of Phospholipid Transfer Protein Activity to HDL and Apolipoprotein B-Containing Lipoproteins in Subjects With and Without Type 1 Diabetes Helen M. Colhoun 1 , Marja-Riitta Taskinen 2 , James D. Otvos 3 , Paul van den Berg 4 , John O’Connor 2 and Arie Van Tol 4 1 Royal Free and University College London Medical School, London, U.K. 2 University of Helsinki Hospital, Helsinki, Finland 3 Liposcience Inc., Raleigh, North Carolina 4 Department of Biochemistry, Cardiovascular Research Institute COEUR, Erasmus University, Rotterdam, the Netherlands Abstract Patients with type 1 diabetes have greatly increased phospholipid transfer protein (PLTP) activity and have an altered HDL subclass distribution. In 195 patients with type 1 diabetes and in 194 men and women aged 30–55 years, we examined the relationship of PLTP activity to HDL and examined whether PLTP activity contributes to differences in HDL found in type 1 diabetes. PLTP activity was measured using an exogenous substrate assay. Average HDL particle size and HDL subclasses were measured using nuclear magnetic resonance spectroscopy. Apolipoprotein AI (apoAI) and apoAII were measured by immunoturbidimetry. The amount of apoAI present in LpAI was measured using a differential electroimmunoassay, and the amount of apoAI in LpAIAII was inferred from the apoAI and LpAI data. Higher PLTP activity was associated with more large HDL ( P < 0.001) and less small HDL ( P < 0.01), more apoAI and apoAII (both at P < 0.001), and more apoAI in both LpAI and LpAIAII ( P = 0.02 and P < 0.001, respectively). These associations were independent of other lipids and enzyme activities. Adjusting for PLTP activity halved the difference between subjects with and without diabetes in apoA1 (from 10.1 mg/dl higher in subjects with diabetes to 4.6 mg/dl higher) and large HDL (2.4 μmol/l higher to 1.2 μmol/l higher) and reduced the difference in HDL size (from 0.31 nm higher to 0.26 nm higher). PLTP activity was also positively associated with apoB, total VLDL and LDL particle number, and IDL level in subjects with diabetes. These data support the idea that PLTP is a major factor in HDL conversion and remodeling in humans and that higher PLTP activity makes an important contribution to the higher apoAI levels and altered HDL subclass distribution in type 1 diabetes. They also support a role for PLTP in the metabolism of apoB-containing lipoproteins. Footnotes Address correspondence and reprint requests to Helen M. Colhou