Mechanisms
Recombination experiments trace accelerated cholesteryl ester transfer in IDDM to a CETP-containing plasma fraction (Eur J Clin Invest 1994)
Original title: Contribution of glycaemic control, endogenous lipoproteins and cholesteryl ester transfer protein to accelerated cholesteryl ester transfer in IDDM
Building on earlier work showing that mass transfer of cholesteryl ester from HDL to apoB-containing lipoproteins is accelerated in insulin-dependent diabetes mellitus, this study used an isotopic method to confirm the rate of transfer of radiolabelled HDL-cholesteryl ester to VLDL plus LDL was also significantly faster in IDDM plasma (IDDM k equals 0.256 plus or minus 0.07; control k equals 0.092 plus or minus 0.05, P less than 0.001). Fasting glucose and fructosamine correlated with both isotopic transfer (r equals 0.54, P equals 0.009, and r equals 0.57, P equals 0.005) and mass transfer at 2 hours (r equals 0.55, P equals 0.006, and r equals 0.59, P equals 0.004). Recombination experiments mixing lipoprotein fractions from IDDM and control subjects showed isotopic transfer was accelerated both when IDDM VLDL was paired with control HDL and density-greater-than-1.21 fractions, and when IDDM density-greater-than-1.21 fractions containing CETP were paired with control VLDL, LDL, and HDL, implicating both VLDL dysfunction and the CETP-containing plasma fraction in the accelerated transfer.
Original abstract
In an earlier study we demonstrated that the transfer of cholesteryl ester (CET) estimated as the net mass of CE lost from HDL to the apoB-containing lipoproteins (VLDL + LDL) during incubation of plasma is accelerated in normolipidaemic patients with insulin-dependent diabetes mellitus (IDDM). Recombination experiments with isolated lipoprotein fractions employing this same mass transfer assay indicated that this disturbance resulted from dysfunction of VLDL and not from changes in the activity of CE transfer protein (CETP). In this study, we sought first to determine whether CET estimated with an isotopic method that measures the transfer of radiolabelled CE from exogenous HDL from non-diabetic controls to endogenous VLDL + LDL was also increased in IDDM and, if so, the extent to which this disturbance was affected by glycaemic control, VLDL and CETP. As observed with the mass transfer assay, the rate of transfer of the HDL-CE label to VLDL + LDL was also significantly accelerated in IDDM plasma (IDDM: k = 0.256 +/- 0.07; control: k = 0.092 +/- 0.05; mean +/- SD; P < 0.001). Fasting glucose and fructosamine correlated with both isotopic transfer (k) (r = 0.54, P = 0.009; r = 0.57, P = 0.005, respectively) and the mass of CE transferred at 2 h (r = 0.55, P = 0.006; r = 0.59, P = 0.004, respectively). Recombination experiments revealed that isotopic CET was accelerated when: (a) IDDM VLDL were combined with controls HDL and d > 1.21 fractions; and (b) IDDM d > 1.21 plasma fractions containing CETP were combined with controls VLDL + LDL and HDL.(ABSTRACT TRUNCATED AT 250 WORDS)
Summary written by cetpinhibition.org from the published abstract; figures as published. Page updated 18 August 2026. Methods.