Abstract 114: Correlation of Specific HDL Subspecies with Arterial Stiffness in Youth with Type 2 Diabetes
Human epidemiological studies demonstrate that increased HDL cholesterol (HDL-C) concentrations are associated with a decreased risk of cardiovascular disease. However, recent drug therapies designed to raise plasma HDL-C concentrations have failed to reduce cardiovascular events. These findings suggest that the cardio-protective effects of HDL may lie in specific HDL subspecies and not in the HDL-C number. Thus, we sought to define the composition of HDL in adolescents with T2D and determine whether specific HDL subspecies are associated with early markers of arterial disease.
Youth with T2D (n=10) and two control groups lean (n=9) and obese (n=11) adolescents were recruited in a cross sectional study. Plasma was separated into 18 fractions using gel filtration chromatography. Lipid associated proteins were then isolated and identified using mass spectrometry. Concurrently, arterial thickness and stiffness measures including common/bulb/internal carotid intima media thickness (IMT) and pulse wave velocity (PWV) were measured.
Compared to lean and obese controls, youth with T2D exhibited decreased phospholipid content in fractions containing large HDL subspecies that was inversely associated with pulse wave velocity (p<0.001). No association between HDL-C and pulse wave velocity was seen. Proteomic analysis of the HDL sized fractions demonstrated decreases in 17 of 45 identified proteins in the T2D group compared to lean youth. The most striking protein decreases occurred in apolipoprotein (apo) A-1, apoC-I, apoE and paraoxonase-1 (p<0.05) in fractions associated with large HDL particles.
Our data demonstrate early changes in the lipid and protein compositions of specific HDL subspecies in adolescents with T2D that are related to early markers of arterial disease. These findings suggest that analyzing the composition of HDL, rather than HDL-C, may be useful in assessing cardiovascular risk in this population.
- © 2013 by American Heart Association, Inc.