Contribution of glycaemic control, endogenous lipoproteins and cholesteryl ester transfer protein to accelerated cholesteryl ester transfer in IDDM.
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)
Ritter
M C
MC
Rush-Presbyterian-St. Luke's Medical Center, Department of Medicine, Chicago, IL 60612-3833.
Bagdade
J D
JD
D000328:Adult; D001786:Blood Glucose / Q000032:analysis*; D002352:Carrier Proteins / Q000502:physiology*; D053480:Cholesterol Ester Transfer Proteins; D002788:Cholesterol Esters / Q000378:metabolism*; D003922:Diabetes Mellitus, Type 1 / Q000378:metabolism*; D005260:Female; D006023:Glycoproteins; D006801:Humans; D008074:Lipoproteins / Q000502:physiology*; D008297:Male; D008875:Middle Aged
D001786:Blood Glucose; C506642:CETP protein, human; D002352:Carrier Proteins; D053480:Cholesterol Ester Transfer Proteins; D002788:Cholesterol Esters; D006023:Glycoproteins; D008074:Lipoproteins