Accelerated cholesteryl ester transfer in noninsulin-dependent diabetes mellitus

Alterations in core lipid composition of lipoproteins in noninsulin-dependent diabetes mellitus (NIDDM) patients have suggested that the heteroexchange of neutral lipids between HDL and the apo B-containing lipoproteins may be enhanced. For this reason, we studied cholesteryl ester transfer (CET) in ten sulfonylurea-treated patients with stable NIDDM. 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 < 0.001); 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 mass of CE transferred at 1 h and diabetic control expressed as plasma fructosamine (r = 0.58, P < 0.09). To characterize this disturbance in CET further, the donor (HDL + VHDL) and acceptor (VLDL + LDL) lipoprotein fractions were isolated by ultracentrifugation at d 1.063 g/ml from 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 and control acceptor lipoproteins resulted in an accelerated CET response identical to that observed in NIDDM whole plasma. This observation indicated that the abnormality in CET in NIDDM was associated with the VLDL + LDL fraction.(ABSTRACT TRUNCATED AT 250 WORDS)