Rates of cholesterol esterification and esterified cholesterol net mass transfer between high-density lipoproteins and apolipoprotein B-containing lipoproteins in Type 1 diabetes.
OBJECTIVE
Type 1 diabetes is associated with a high incidence of coronary heart disease (CHD) despite paradoxically normal or high high-density lipoprotein (HDL) cholesterol concentrations. Triglyceride (TG) concentrations have been shown to be important determinants of two aspects of HDL metabolism: cholesterol esterification rate and esterified cholesterol (EC) net mass transfer rate between HDL and the apolipoprotein B-containing lipoproteins. In order to try to explain the paradox, we aimed to assess the relationships between plasma TG and these two processes in Type 1 diabetic compared with non-diabetic subjects.


METHODS
Rates of cholesterol esterification and EC net mass transfer between HDL and the apolipoprotein B-containing lipoproteins were assessed by incubating whole plasma at 37 degrees C; intra-assay coefficients of variation were 6% and 30%, respectively.


RESULTS
Ten Type 1 diabetic and 10 non-diabetic subjects, with similar ages, sex distributions, body mass indices and total cholesterol and TG concentrations, were assessed. Apolipoprotein A1, HDL unesterified cholesterol, and HDL phospholipid concentrations were greater in the Type 1 diabetic subjects. There were no significant differences in the rates of cholesterol esterification or EC net mass transfer between the groups. There were strong associations between plasma TG and the rate of cholesterol esterification and between plasma TG and the rate of EC net mass transfer in Type 1 diabetic subjects (r = 0.83, P = 0.0027 and r = 0.88, P = 0.0009, respectively) and in non-diabetic subjects (r = 0.91, P = 0.0002 and r = 0.79, P = 0.0070, respectively). However, the slopes of the associations with plasma TG were significantly steeper in the Type 1 diabetic subjects (analyses of covariance P = 0.0053 and P = 0.0146, respectively).


CONCLUSIONS
Increases in TG may therefore promote more EC enrichment of atherogenic apolipoprotein B-containing lipoproteins in Type 1 diabetes while also promoting more cholesterol esterification, thereby maintaining HDL cholesterol concentrations. This could contribute to the paradox of high CHD incidence despite normal or high HDL cholesterol concentrations in Type 1 diabetes.
Valabhji
J
J
Department of Endocrinology, Imperial College School of Medicine, St Mary's Hospital, London, UK. j.valabhji@ic.ac.uk
Donovan
J
J
McColl
A J
AJ
Schachter
M
M
Richmond
W
W
Elkeles
R S
RS
D000328:Adult; D016632:Apolipoprotein A-I / Q000097:blood; D001055:Apolipoproteins B / Q000097:blood*; D019540:Area Under Curve; D001786:Blood Glucose / Q000378:metabolism; D002784:Cholesterol / Q000097:blood*; D002788:Cholesterol Esters / Q000097:blood*; D008076:Cholesterol, HDL / Q000097:blood*; D008078:Cholesterol, LDL / Q000097:blood; D015243:Cholesterol, VLDL / Q000097:blood; D002914:Chylomicrons / Q000097:blood; D003922:Diabetes Mellitus, Type 1 / Q000097:blood*; D005215:Fasting; D005260:Female; D006801:Humans; D008297:Male; D012016:Reference Values; D012044:Regression Analysis; D012907:Smoking; D014280:Triglycerides / Q000097:blood
D016632:Apolipoprotein A-I; D001055:Apolipoproteins B; D001786:Blood Glucose; D002788:Cholesterol Esters; D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D015243:Cholesterol, VLDL; D002914:Chylomicrons; D014280:Triglycerides; D002784:Cholesterol