ACCELERATED CHOLESTERYL ESTER TRANSFER IN NONINSULIN-DEPENDENT DIABETES-MELLITUS

Alterations in core lipid composition of lipoproteins in noninsulin-de pendent diabetes mellitus (NIDDM) patients have suggested that the het eroexchange of neutral lipids between HDL and the apo B-containing lip oproteins may- be enhanced. For this reason, we studied cholesteryl es ter transfer (CET) in ten sulfonylurea-treated patients with stable NI DDM. CET measured in all NIDDM subjects with an assay of mass transfer was significantly greater than that of controls at 1 and 2 h (P < 0.0 01); the transfer of radiolabeled CE also was increased in a subset of four of the NIDDM group (NIDDM k = 0.21 +/- 0.04 vs. control k = 0.10 +/- 0.05;P < 0.05). A weak correlation was demonstrable between the m ass of CE transferred at 1 h and diabetic control expressed as plasma fructosamine (r = 0.58, P < 0.09). To characterize this disturbance in C;ET further, the donor (HDL + VHDL) and acceptor (VLDL + LDL) lipopr otein fractions were isolated by ultracentrifugation at d 1.063 g/ml f rom NIDDM and control plasma and a series of recombination experiments were performed. Combining NIDDM acceptor with control donor fractions that contained HDL and CETP and not the combination of NIDDM donor an d control acceptor lipoproteins resulted in an accelerated CET respons e identical to that observed in NIDDM whole plasma. This observation i ndicated that the abnormality in CET in NIDDM was associated with the VLDL + LDL fraction. To discern which lipoprotein class was dysfunctio nal, VLDL (d < 1.006 g/ml) and LDL (d 1.006-1.063 g/ml) from NIDDM and control subjects were isolated and combined with the d > 1.063 g/ml f ractions of their respective control at the same triglyceride concentr ation for VLDL and cholesterol for LDL. These experiments revealed tha t NIDDM VLDL and not LDL promoted CET. Concentrations of cholesteryl e ster transfer protein (CETP) did not differ in the two groups (NIDDM 1 .63 +/- 0.36 mu g/ml vs. control 1.33 +/- 0.36). These findings indica te that CET is increased in the plasma of NIDDM patients, and this abn ormality appears to result from dysfunction of VLDL. Since this abnorm ality may promote the generation of increased numbers of potentially a therogenic cholesteryl ester-enriched apo B-containing lipoproteins, i t may be a previously unrecognized risk factor that contributes to the development of macrovascular complications in NIDDM.