Are diabetes mellitus and lipoprotein(a) independently or causally associated with an increased cardiovascular risk?

Serum Lp(a) and diabetes mellitus increase the risk of cardiovascular diseases (CVD). However, the relationship between serum Lp(a) and diabetes is poorly characterized, and it is a subject of debate as to whether they are independently or causally associated (1). One of the atherogenic mechanisms in hyperglycemia is based on enhanced inflammation. Diabetes is associated with increased vascular production of reactive oxygen species (ROS), which causes premature cell apoptosis via reduction of endothelial nitric oxide (NO), resulting in decreased smooth muscle relaxation and antiatherogenic properties, including decreased platelet aggregation and adhesion inhibition (1). Another important atherogenic mechanism is the lipid fractions effect. Diabetic dyslipidemia consists of elevated triglyceride-rich lipoproteins (VLDLs) and VLDL remnants and low HDL-C levels. LDL particles are converted to smaller, more atherogenic lipoproteins known as “small-dense LDLs.” Diabetic dyslipidemia is due to insulin resistance and hyperglycemia. The diminished insulin action increases ApoB synthesis, and the end products of this process are small-dense LDL particles with reduced LDL receptor-binding affinity, greater penetration in the arterial wall, and increased oxidation susceptibility, leading to atherogenesis. The Strong Heart Study showed that there is a stepwise decrease in LDL size according to diabetic status. This association is more striking in women than in men (1).