Clinical significance of the physicochemical properties of LDL in type 2 diabetes

Abstract

Atherosclerosis is the leading cause of death in type 2 diabetes. LDL cholesterol and atherosclerosis are related, both in healthy people and those with diabetes; however, people with diabetes are more prone to atheroma, even though their LDL cholesterol levels are similar to those in their non-diabetic peers. This is because LDL particles are modified in the presence of diabetes to become more atherogenic. These modifications include glycation in response to high plasma glucose levels; oxidative reactions mediated by increased oxidative stress; and transfer of cholesterol ester, which makes the particles smaller and denser. The latter modification is strongly associated with hypertriglyceridaemia. Oxidatively and non-oxidatively modified LDL is involved in plaque formation, and may thus contribute to the accelerated atherosclerosis. This review discusses the techniques currently used to determine the physicochemical properties of LDL, and examines the evidence that modification of these properties plays a role in the accelerated atherosclerosis associated with type 2 diabetes.

Effect of three consecutive meals on the physicochemical properties of HDL and LDL in individuals with the metabolic syndrome and patients with type 2 diabetes

“…The prolonged hypertriglyceridemia following three consecutive meals in males with the MetS and patients with T2DM results in the formation of triglyceride-enriched HDL and LDL particles Insulin resistant states, including the MetS and T2DM, are associated with decreased plasma HDL cholesterol concentration, whereas LDL cholesterol concentration is usually normal. However, in T2DM the metabolism of LDL is modified, rendering the lipoprotein particles more atherogenic (Scheffer et al, 2005). Furthermore, it has been shown that high-fat intake is associated with oxidative stress.…”

Messenger RNA levels of genes involved in dysregulation of postprandial lipoproteins in type 2 diabetes: the role of Niemann–Pick C1-like 1, ATP-binding cassette, transporters G5 and G8, and of microsomal triglyceride transfer protein

“…In diabetes, a condition with accelerated atherosclerosis, LDL cholesterol is frequently normal although compositional differences have been described [42]. The postprandial lipoproteins are known to influence LDL composition [43], but are also atherogenic in their own right [5], and it is probably of considerable importance that there is a specific Apo B48 receptor on the macrophage [44].…”

A novel truncated form of apolipoprotein A-I transported by dense LDL is increased in diabetic patients

“…Several studies have reported different LDL modifi cations in diabetics due to oxidation and glycosylation, resulting in the presence of more atherogenic LDL particles in these patients ( 47 ). Indeed, the increased cardiovascular risk of DM patients has been related to the presence of small dense LDL particles ( 48 ), which have been shown to be more atherogenic and may explain, at least in part, the higher risk of those patients even having similar LDLcholesterol plasma concentrations than control subjects ( 49 ).…”