Adenosine triphosphate binding cassette transporter G1-mediated cholesterol efflux to serum is impaired in type 2 diabetes mellitus

Abstract

RESULTS: Cholesterol efflux from cells is an early step of reverse cholesterol transport and is mediated by regulated transporter-facilitated processes and aqueous diffusion. Adenosine triphosphate binding cassette transporter G1 (ABCG1) has recently been identified as an important cholesterol transporter that mediates cholesterol efflux from cells to mature HDL. Our aim is to evaluate the capacity of serum to induce ABCG1-mediated cellular cholesterol efflux in patients with type 2 diabetes mellitus and its relationship to glycemic control and inflammation.60 diabetic patients and 50 age-matched healthy controls were recruited. Serum capacity to induce cholesterol efflux was determined by measuring the transfer of [3H]cholesterol from human ABCG1-transfected CHO-K1 cells to the medium containing the tested serum. Plasma high sensitivity C-reactive protein (hs-CRP) was measured by an immunoturbidimetric assay and HbA1c by ion-exchange high performance liquid chromatography. The diabetic patients had significantly higher plasma triglyceride and hs-CRP, and lower HDL than controls. Serum cholesterol efflux capacity was reduced in diabetic patients (2.6 ± 1.4% vs 4.1 ± 1.8%, p<0.01) and remained significant even after adjusting for HDL level. Serum cholesterol efflux capacity correlated with HDL only in the controls (r=0.32, p=0.03) but not in the diabetic patients. There was no significant association between serum cholesterol efflux capacity and HbA1c but an inverse correlation between serum cholesterol efflux capacity and log(hs-CRP) was seen in the diabetic patients (r=-0.42, p=0.01). In conclusion, the capacity of whole serum to stimulate cholesterol efflux from cells provided integrated information on lipoproteins and serum components involved in promoting cholesterol efflux from cells. We have shown that the capacity of serum to induce ABCG1-mediated cholesterol efflux was impaired in diabetic patients and this process was related to the degree of subclinical inflammation.