Impaired functionality of HDL in diabetes

Abstract

Patients with type 2 diabetes mellitus (T2DM) remain at higher risk of cardiovascular diseases than nondiabetic subjects even when they have achieved the recommended targets of serum lipids, blood glucose and blood pressure. A growing body of recent investigations suggests that the characteristics of plasma lipoproteins may be altered in such conditions. It is now accepted that a low concentration of highdensity lipoprotein cholesterol (HDL-C) is the most common lipoprotein abnormality in patients with coronary heart disease (CHD), and the level of HDL-C serves as the strongest prediction of CHD risk [1]: for every 1 mg/dl increase in HDL-C, the predicted incidence of coronary events decreases by 2% in men and 3% in women. Besides, low HDL-C is also associated with unfavorable prognosis in patients with CHD. Even with the most aggressive lowdensity lipoprotein-cholesterol (LDL-C) intervention, two thirds of all cardiovascular events are not prevented. Combination therapy involving the addition of aggressive HDL-based interventions may potentially improve this number. Conventional treatment to raise HDL-C includes lifestyle modifications, exercise, smoking cessation, weight control, moderate alcohol intake, a diet rich in n-3 polyunsaturated fatty acids with limited carbohydrates, niacin, fibrates and statins. HDL forms a structurally and functionally heterogeneous class of lipoproteins. Most of them contain apolipoprotein (apo) A-I as the most abundant protein constituent of the water-soluble surface. The bulk of HDL is formed by spherical particles containing a core of water-insoluble cholesteryl ester. Apo A-I and apo A-II also have biological actions such as receptor binding and the modulation of several enzymes. In addition to these major apolipoproteins, certain HDL subclasses have enzymes such as lecithincholesterol acyltransferase (LCAT), cholesteryl-estertransfer protein (CETP), phospholipid transfer protein (PLTP), anti-oxidative enzymes or bioactive lipids on the surface.