Impaired macrophage cholesterol efflux in poorly controlled type 2 diabetes mellitus

Abstract

Macrophage foam cell formation plays an important role in the development of atherosclerosis. Accumulation of cholesterol in macrophages is partly influenced by the cells’ capability to efflux cholesterol to extracellular cholesterol acceptors. We have evaluated whether there were changes in macrophage cholesterol efflux in patients with poorly controlled type 2 diabetes. Forty type 2 diabetic patients and fifty non-diabetic controls were recruited. Peripheral blood monocytes were isolated and differentiated into macrophages using autologous serum. Cholesterol efflux assay was performed by measuring the percentage of [3H]cholesterol transferred from subject’s monocyte-derived macrophages to fixed concentrations of exogenous apolipoprotein (apo) AI, HDL, HDL2 and HDL3 as cholesterol acceptors. Diabetic patients had elevated triglyceride and lower HDL than controls. As expected, HbA1c was much higher in diabetic patients than control (9.3% ± 0.9 vs 5.4% ± 0.5, p<0.01). In type 2 diabetic patients, macrophage cholesterol efflux to apo AI (18.9% ± 9.5 vs 26.8% ± 10.5, p<0.01) and to HDL (34.2% ± 7.8 vs 43.8% ± 8.6, p<0.01) was significantly impaired compared to controls. Similar reduction in cholesterol efflux to HDL2 and HDL3 was also observed. Macrophage cholesterol efflux to apo AI (r = -0.39, p<0.01) and HDL (r = -0.53, p<0.01) correlated inversely with HbA1c. In conclusion, macrophage cholesterol efflux was significantly impaired in poorly controlled patients with type 2 diabetes mellitus and might contribute to their increased risk of developing cardiovascular diseases. Whether improvement in glycaemic control will restore macrophage cholesterol efflux warrants further investigations.