Abstract 15852: Determinants of HDL Efflux in Diabetes and Cardiovascular Disease
Although low HDL-C predicts cardiovascular disease (CVD), recent trials of agents that raise HDL-C did not demonstrate CVD benefit. Thus, there is a need for better understanding HDL function. HDL cholesterol efflux appears to be an important determinant of atherosclerosis and CVD. However, levels of HDL-C and Apo A1 do not fully explain changes in HDL efflux. To better understand determinants of HDL efflux in disease states, we measured rates of cholesterol efflux from ABCA1 transfected BHK cells using HDL isolated by ultracentrifugation from 137 subjects with and without type 2 diabetes (T2DM) and CVD. We also measured levels of 60 HDL proteins, with purported involvement in lipid metabolism, complement regulation, acute phase response, and protease inhibition and Apo A1 methionine oxidations by quantitative proteomics using Multiple Reaction Monitoring (MRM) with stable isotope standards. We also measured functional activity of PLTP, CETP, LCAT and total prebeta-1 by ELISA.
Results: Patients with diabetes irrespective of HDL-C or CVD had lower efflux than age matched non-diabetic controls (P< 0.001). The mean efflux did not differ between patients with and without low levels of HDL (table) and the correlation between HDL-C and efflux was R=0.3 (P=0.008). Efflux positively correlated with prebeta-1, LCAT, Apo AII (P<0.01), and negatively correlated with onset of diabetes, Apo A IV, CVD and aspirin use ( P<0.01). After doing a stepwise regression for the significant covariates, duration of diabetes was the single most significant predictor of efflux change with 0.1% drop with every 1 additional year of diabetes duration (P=0.007).
Conclusion: longer duration of diabetes is associated with compromised HDL efflux capacity that is independent of HDL-C, Apo A1 and other measured HDL proteins. These results suggest other relevant determinants of cholesterol efflux in T2DM.
- © 2012 by American Heart Association, Inc.