Abnormalities in apo B-containing lipoproteins in diabetes and atherosclerosis

Abstract

Atherosclerosis is the major cause of death in patients with diabetes. Low-density lipoprotein (LDL) being the most important cholesterol-carrying lipoprotein has been studied extensively in both diabetes and non-diabetes. This paper reviews the literature but also focuses on the precursors of LDL and in particular the postprandial apo B-containing lipoproteins. Abnormalities in the postprandial lipoproteins and alteration in chylomicron assembly and clearance are discussed and the evidence presented suggesting the importance of dysregulation of these lipoproteins in atherosclerotic progression. The relationship between chylomicron production in the intestine and hepatic release of very low-density lipoproteins (VLDL) is explored, as is the interrelationship between clearance rates of these lipoproteins. The size of LDL influences its atherogenicity. VLDL composition and size in relation to its influence on LDL is discussed. The effect of diet on the composition of lipoproteins and the relationship between fatty acid composition and clearance is reviewed. Evidence that diabetic control beneficially alters lipoprotein composition is presented suggesting how improved diabetic control may reduce atherosclerosis. The review concludes with a discussion on the effect of the apo B-containing lipoproteins and their modification through glycation and oxidation on macrophage and endothelial function.

Diabetic dyslipidaemia: from basic research to clinical practice*

“…Triglycerides in large lipoproteins are hydrolyzed faster than in smaller particles. Thus, the flux of chylomicrons after a fatrich meal will impede the lipolysis of VLDL particles due to the competion for the contact with LPL [8,78,84,85,86]. Consequently the delipidation process of VLDL particles are slowed down and the residence time of these particles in circulation is prolonged.…”

“…The carrier status of LPL gene mutations that are relatively common like N291S and D9 N, can aggravate the postprandial lipemia [88,89]. A third potential mechanism is the impaired clearance of remnant particles by liver receptors (LDL receptor and LRP) [85,86]. Lipoprotein uptake is preceeded by trapping of remnants in the vicinity of receptors.…”

“…The induction of the insulin resistant state in fructose-fed hamsters is associated with overproduction of apo B 48 containing particles [91]. There is also evidence that intestinal MTP is increased in diabetic animals and this could enhance the formation of apo B 48 containing particles [86,91]. Further studies are needed to delineate the exact contribution of intestinal overproduction of apo B 48 lipoproteins in diabetes to the postprandial lipemia in humans.…”

“…A number of studies have shown that postprandial lipemia is linked with the endothelial dysfunction and generation of oxidative stress in Type 2 diabetic patients [92,93,94,95]. Remnant particles particularly cholesterol ester rich remnants are considered to be highly atherogenic [8,9,78,85,86]. Recent data suggest that apo B 48 and apo B 100 containing lipoproteins are probably equally atherogenic [96].…”

“…The most powerful atherogenic components are (i) small dense LDL, (ii) remnant particles, and (iii) the low concentration of HDL with its unfavorable compositional alterations. The coexistence of these three factors strongly aggravates the lipid accumulation in arterial wall and the formation of plaques [7,9,86,126,139]. Consequently all three factors should be the targets of therapy.…”