CETP-mediated cholesteryl ester enrichment of apoB subclasses in type 1 diabetes

Accelerated cholesteryl ester transfer (CET) in patients with types 1 (T1D) and 2 diabetes enhances the atherogenicity of the apoB-containing CE acceptor lipoproteins. The study of lipoprotein density fractions cannot identify which of the five immunologically distinct apoB subclasses function as CE acceptors because they are heterogeneous and present in very low-, intermediate- and low density lipoproteins (VLDL, IDL and LDL, respectively). In order to design lipid-modifying therapies that specifically target these CE-enriched lipoprotein particles, it is necessary to first characterize their CE acceptor function.

To identify the CE acceptors, we estimated CE net mass transfer to the apoB subclasses LpB:C, LpB:E + LpB:C:E, LpB and LpAII:B:C:D:E from changes in neutral lipids measured by gas chromatography following their separation by sequential immunoaffinity chromatography in the plasma of 12 patients with T1D and six control subjects. In both groups, CE was distributed equally to LpB:E + LpB:C:E and LpB:C. In the T1D CE acceptors, however, both the magnitude of the increase (18% vs. 10%; P < 0·01) and the per particle mass of CE transferred were significantly greater than in controls (T1D: 2·29 μmol ± 2·1 vs. control 0·43 ± 0·43/mg apoB; P < 0·047).

While LpB:E + LpB:C:E and LpB:C functioned as CE acceptors in both groups, these subclasses increased their CE content to a greater degree and accrued more CE per particle in the patients with T1D. As this disturbance in lipoprotein remodelling may increase the cholesterol burden and potential atherogenicity of these apoB subclasses, it may be a previously unrecognized factor that increases cardiovascular risk in patients with T1D.