Purpose of review: To highlight the potential importance of glycation as an atherogenic modification of LDL, factors determining glycated apolipoprotein B in vivo and susceptibility of LDL to glycation in vitro. We also discuss the distribution of glycated apolipoprotein B across different LDL subfractions in healthy controls, patients with type 2 diabetes and metabolic syndrome.
Recent findings: Small, dense LDL, which is known to be most closely associated with atherogenesis, is more preferentially glycated in vivo and more susceptible to glycation in vitro than more buoyant LDL. Glycation and oxidation of LDL appear to be intimately linked. In patients with type 2 diabetes, plasma glycated apolipoprotein B correlated with small, dense LDL apolipoprotein B, but not with HbA1c. Glycated apolipoprotein B is significantly lower in statin-treated type 2 diabetes compared with those not on statins.
Summary: Glycation of LDL occurs chiefly because of the nonenzymatic reaction of glucose and its metabolites with the free amino groups of lysine of which apolipoprotein B is rich. Higher concentrations of glycated LDL are present in diabetes than in nondiabetic individuals and metabolic syndrome. Even in nondiabetic individuals, however, there is generally more circulating glycated LDL than oxidatively modified LDL. Probably, oxidation and glycation of LDL are partially interdependent and indisputably coexist, and both prevent LDL receptor-mediated uptake and promote macrophage scavenger receptor-mediated LDL uptake. The recognition that LDL glycation is at least as important as oxidation in atherogenesis may lead to improvements in our understanding of its mechanism and how to prevent it.