EVALUATION OF SERUM CHOLESTEROL EFFLUX CAPACITY IN DIABETIC COMPARED TO HEALTHY SUBJECTS

Objectives: HDL provide cardiovascular protection by promoting reverse cholesterol transport (RCT). Efflux of cell cholesterol to HDL, the first step of RCT, can occur through aqueous diffusion, SR-BI, ABCG1 and ABCA1. Serum cholesterol efflux capacity (CEC), an index of HDL functionality, depends of HDL levels but is also strictly related to HDL composition. The aim of this study is to measure serum CEC in patients with diabetic dyslipidemia (DD) (n¼116) and in apparently healthy control subjects (HS) (n¼94) and to correlate serum CEC with preclinical atherosclerosis (IMT). Methods: ABCA1-mediated CEC of sera from diabetic patients and from healthy subjects was measured in J774 macrophages induced to express high level of ABCA1 protein after treatment with cAMP and efflux of cholesterol was quantified by an in vitro technique that traces the release of 3H-cholesterol to apoA-I. Results: ABCA1-mediated CEC was higher in DD than in HS (4.8791.19% vs. 3.5651.07%; p<0.001). ABCA1 serum CEC showed a borderline significant inverse correlation with IMT in HS (r¼-0.0296; p¼0.078); on the other hand, a positive association between ABCA1-mediated CEC and IMT was found in DD patients (r¼0.2363; p¼0.047). After adjustment for lipoprotein- related parameters, the inverse correlation between ABCA1- mediated CEC and IMT in HS became stronger (r¼-0.0353; p¼0.053), while the positive association between ABCA1-mediated CEC and IMT in DD patients was lost (r¼0.0169; p¼0.141). Moreover preliminary results suggest an inverse association between TG levels and ABCA1-mediated CEC in DD patients but not in HS. Conclusion: In conclusion the inverse relationship between ABCA1-mediated CEC and a surrogate marker of atherosclerosis found in healthy subjects, resulted entirely reversed in diabetic patients, possibly due to modification in lipoprotein composition. The clinical relevance of this finding needs further investigation.