High-Density Lipoprotein Subspecies in Health and Human Disease: Focus on Type 2 Diabetes

Plasma cholesterol levels of high-density lipoproteins (HDL) have been associated with cardioprotection for decades. However, there is an evolving appreciation that this lipoprotein class is highly heterogeneous with regard to composition and functionality. With the advent of advanced lipid-testing techniques and methods that allow both the quantitation and recovery of individual particle populations, we are beginning to connect the functionality of HDL subspecies with chronic metabolic diseases. In this review, we examine type 2 diabetes (T2D) and explore our current understanding of how obesity, insulin resistance, and hyperglycemia affect, and may be affected by, HDL subspeciation. We discuss mechanistic aspects of how insulin resistance may alter lipoprotein profiles and how this may impact the ability of HDL to mitigate both atherosclerotic disease and diabetes itself. Finally, we call for more detailed studies examining the impact of T2D on specific HDL subspecies and their functions. If these particles can be isolated and their compositions and functions fully elucidated, it may become possible to manipulate the levels of these specific particles or target the protective functions to reduce the incidence of coronary heart disease.