Low density lipoprotein non-esterified fatty acids and lipoprotein lipase in diabetes.
OBJECTIVE
Fatty acid metabolism is disturbed in poorly controlled diabetes. Low density lipoprotein (LDL) oxidation, thought to be an atherogenic modification, is partly dependent on LDL fatty acid content whether it be in the form of cholesteryl ester, phospholipids, triglyceride or non-esterified fatty acid (NEFA). Lipoprotein lipase (LPL) is deficient in diabetic patients. Lipoprotein lipase bound to LDL may facilitate cholesterol accumulation in the artery wall through the attachment of LDL to the proteoglycans expressed on endothelial cells and collagen. The purpose of this study was to examine the degree of binding of fatty acids and lipoprotein lipase to LDL in type 2 diabetic patients and to examine the relationship between non-esterified fatty acids attached to LDL and LDL oxidisability.


METHODS
Eight type 2 diabetic patients and eight control subjects were examined fasting and at 4 and 6h following a high fat meal. Six control subjects were examined fasting and 30 min after intravenous heparin. LDL was isolated by sequential ultracentrifugation. Individual LDL non-esterified fatty acids were measured by gas-liquid chromatography following transmethylation. LPL and oxidised LDL were measured by ELISA.


RESULTS
The diabetic patients had HbA1c of 7.8 +/- 0.5% confirming moderate diabetic control. There was a large increase in the mean non-esterified fatty acids on LDL from diabetic subjects (0.66 +/- 0.40 mg/mg versus 0.06 +/- 0.02 mg/mg LDL protein, p < 0.01). Mean LDL cholesterol ester fatty acids were also significantly increased in the diabetic subjects (1.47 +/- 0.58 mg/mg versus 0.57 +/- 0.40 mg/mg LDL protein, p < 0.01). There was a significant increase in oxidised LDL (31.2 +/- 24 mg/mg versus 7.7 +/- 4.5 mg/mg LDL protein, p < 0.01) and a significant correlation between postprandial non-esterified fatty acid and LDL oxidation (r = 0.69, p < 0.05). LPL was significantly increased on the LDL but not in the plasma of diabetic subjects. Acute elevation in non-esterified fatty acids produced by heparin in control subjects did not increase LDL non-esterified fatty acids.


CONCLUSIONS
This study demonstrates that the disturbance in fatty acid metabolism found in type 2 diabetic subjects is associated with a significant increase in non-esterified fatty acids attached to LDL. This may account, at least in part, for the increased oxidation of the LDL and therefore its atherogenicity. The finding of an increase in the amount of LPL bound to LDL suggests an important mechanism to facilitate the uptake of diabetic LDL by endothelial proteoglycans and collagen in the atherosclerotic plaque.
Phillips
Catherine
C
Department of Diabetes and Endocrinology, Trinity College Dublin, Ireland.
Owens
Daphne
D
Collins
Patrick
P
Tomkin
Gerald H
GH
D000368:Aged; D016022:Case-Control Studies; D003924:Diabetes Mellitus, Type 2 / Q000097:blood*; D005230:Fatty Acids, Nonesterified / Q000097:blood / Q000378:metabolism*; D005260:Female; D006801:Humans; D008055:Lipids / Q000097:blood; D008071:Lipoprotein Lipase / Q000097:blood / Q000378:metabolism*; D008077:Lipoproteins, LDL / Q000097:blood / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D019518:Postprandial Period
D005230:Fatty Acids, Nonesterified; D008055:Lipids; D008077:Lipoproteins, LDL; C099252:oxidized low density lipoprotein; D008071:Lipoprotein Lipase