HDL Function in Diabetes

Diabetes mellitus (DM) is a chronic metabolic disorder which is characterized by disturbed insulin secretion and diminished tissue sensitivity to insulin. These disturbances result in impaired cellular glucose transport and hyperglycaemia. The presence of hyperglycaemia is associated with an enhanced inflammatory response and mitochondrial oxidative stress, leading to vascular endothelial dysfunction. Hyperglycaemia is a metabolic feature characteristic for diabetes which over time can cause major health complications. The prevalence of diabetes mellitus is constantly growing worldwide due to the high prevalence of obesity, unhealthy eating habits, and lack of physical activity. The main goal of diabetes management is to achieve appropriate glycaemic control to limit the development of diabetes-related complications, including micro- and macrovascular disorders (atherosclerotic cardiovascular disease), cardiovascular diseases, renal insufficiency and failure, cerebrovascular diseases, dementia, some malignant neoplasms, etc. Both T2DM and insulin resistance are well-known factors significantly enhancing cardiovascular (CV) risk. Dyslipidaemia is found in 60–70% of patients with T2DM. The physiological heterogeneity of HDL in patients with diabetes or CVD is high as a result of the loss/acquisition of some components and/or the modification of other HDL constituents. Compositional modifications of HDL include increased particle size, lower content of cholesterol esters in small HDL3 particles, diminished HDL triacylglycerol content, elevated levels of phospholipid transfer protein (PLTP), CETP and lecithin-cholesterol acyltransferase (LCAT), damage of ApoA-I protein, and altered PL and sphingolipid profiles, affect its functionality, and are associated with enhanced oxidative stress during insulin deprivation. Alterations in HDL size may occur before the onset of diabetes since small HDL particles and positively correlate with future T2DM risk. HDL particles from diabetic patients have also reduced protein content. All the aforementioned modifications significantly decrease anti-atherogenic functions of HDL due to weakened antioxidant, anti-inflammatory, and vasodilator properties, accompanied by impaired HDL cholesterol efflux capacity in patients with T2DM.