Pre-β1 HDL in type 2 diabetes mellitus

Background and aims: Pre-β1 HDL, being a major acceptor of free cholesterol from cells, plays an important role in reverse cholesterol transport. This study was performed to determine whether abnormalities in pre-β1 HDL concentration were present in type 2 diabetes irrespective of their HDL-cholesterol levels, and the impact on cholesterol efflux.

Methods: 640 type 2 diabetic patients with or without cardiovascular disease (CVD) and 360 non-diabetic controls matched for serum HDL-cholesterol levels were recruited. Plasma pre-β1 HDL was measured by ELISA, and cholesterol efflux to serum, mediated by ATP-binding cassette transporter A1 (ABCA1), was determined by measuring the transfer of [3H]cholesterol from cultured cells expressing ABCA1 to the medium containing the tested serum.

Results: Despite the diabetic subjects having matched HDL-cholesterol and total apoA1 as controls, plasma pre-β1 HDL was significantly reduced in both male (p < 0.01) and female diabetic patients (p < 0.05), and patients with CVD had the lowest pre-β1 HDL level. Serum capacity to induce ABCA1-mediated cholesterol efflux was impaired in the diabetic group (p < 0.01) and cholesterol efflux correlated with pre-β1 HDL (Pearson's r = 0.38, p < 0.01), and this association remained significantly even after controlling for age, gender, body mass index, diabetes status, smoking, apoA1, triglyceride and LDL.

Conclusions: Plasma pre-β1 HDL level was significantly decreased in type 2 diabetes and was associated with a reduction in cholesterol efflux mediated by ABCA1. Our data would suggest that low pre-β1 HDL might cause impairment in reverse cholesterol transport in type 2 diabetes.