de Vries R, Kerstens M N, Sluiter W J, Groen A K, van Tol A, Dullaart R P F
Department of Endocrinology, University of Groningen and University Medical Center Groningen, P.O. Box 30.001, Groningen, 9700, The Netherlands.
Diabetologia. 2005 Jun;48(6):1105-13. doi: 10.1007/s00125-005-1760-0. Epub 2005 May 5.
AIM/HYPOTHESIS: Cellular cholesterol efflux to plasma is important in reverse cholesterol transport and may be affected by simvastatin in type 1 diabetes mellitus.
In 14 moderately hypercholesterolaemic type 1 diabetic and 13 healthy men we determined plasma (apo)lipoproteins, pre-beta HDL formation, cholesteryl ester transfer protein (CETP) activity, phospholipid transfer protein (PLTP) activity, cholesterol esterification, cholesteryl ester transfer and the capacity of plasma to induce cholesterol efflux out of Fu5AH cells and fibroblasts. After diet run-in, diabetic patients were randomly treated with simvastatin 10, 20, 40 mg and placebo, once daily each, for 6 weeks in a double-blind crossover design.
Plasma very low density lipid protein (VLDL)+LDL cholesterol, LDL cholesterol, HDL phospholipids, apolipoprotein (apo) A-I, apo B, CETP activity, PLTP activity, cholesterol esterification, cholesteryl ester transfer and the capacity of plasma to induce cholesterol efflux from Fu5AH cells and fibroblasts were higher in diabetic patients. Pre-beta HDL formation was unaltered. Simvastatin treatment decreased VLDL+LDL cholesterol, LDL cholesterol, triglycerides and apo B, CETP activity, cholesterol esterification and cholesteryl ester transfer. HDL cholesterol increased and its change was correlated with the change in cholesteryl ester transfer. The ability to promote cholesterol efflux from Fu5AH cells and fibroblasts did not change after simvastatin.
CONCLUSIONS/INTERPRETATION: The capacity of plasma from moderately hypercholesterolaemic type 1 diabetic patients to induce cholesterol efflux out of Fu5AH cells and fibroblasts is enhanced, probably due to higher apo A-I, HDL phospholipids and PLTP activity. Simvastatin increases HDL cholesterol in type 1 diabetic patients via lowering of plasma cholesteryl ester transfer. The HDL changes after simvastatin do not increase cellular cholesterol efflux further.
目的/假设：细胞内胆固醇向血浆的流出在胆固醇逆向转运中起重要作用，且可能受到辛伐他汀对1型糖尿病的影响。
我们测定了14名中度高胆固醇血症的1型糖尿病男性患者和13名健康男性的血浆（载脂蛋白）脂蛋白、前β高密度脂蛋白形成、胆固醇酯转运蛋白（CETP）活性、磷脂转运蛋白（PLTP）活性、胆固醇酯化、胆固醇酯转运以及血浆诱导Fu5AH细胞和成纤维细胞中胆固醇流出的能力。在饮食导入期后，糖尿病患者采用双盲交叉设计，随机接受10、20、40mg辛伐他汀和安慰剂治疗，每日一次，共6周。
糖尿病患者的血浆极低密度脂蛋白（VLDL）+低密度脂蛋白胆固醇、低密度脂蛋白胆固醇、高密度脂蛋白磷脂、载脂蛋白（apo）A-I、apo B、CETP活性、PLTP活性、胆固醇酯化、胆固醇酯转运以及血浆诱导Fu5AH细胞和成纤维细胞中胆固醇流出的能力较高。前β高密度脂蛋白形成未改变。辛伐他汀治疗降低了VLDL+低密度脂蛋白胆固醇、低密度脂蛋白胆固醇、甘油三酯和apo B、CETP活性、胆固醇酯化和胆固醇酯转运。高密度脂蛋白胆固醇增加，其变化与胆固醇酯转运的变化相关。辛伐他汀治疗后，促进Fu5AH细胞和成纤维细胞中胆固醇流出的能力未改变。
结论/解读：中度高胆固醇血症的1型糖尿病患者血浆诱导Fu5AH细胞和成纤维细胞中胆固醇流出的能力增强，可能是由于较高的apo A-I、高密度脂蛋白磷脂和PLTP活性。辛伐他汀通过降低血浆胆固醇酯转运增加1型糖尿病患者的高密度脂蛋白胆固醇。辛伐他汀治疗后的高密度脂蛋白变化并未进一步增加细胞胆固醇流出。
