Bagdade J D, Ritter M C, Subbaiah P V
Department of Medicine, Rush Presbyterian-St Luke's Medical Center, Chicago, IL 60612.
Eur J Clin Invest. 1991 Apr;21(2):161-7. doi: 10.1111/j.1365-2362.1991.tb01805.x.
Abnormalities in cholesteryl ester transfer (CET) may play a role in the development of diabetic arterial vascular complications. To assess this important step systematically in reverse cholesterol transport, we have studied 20 treated, clinically stable, normolipidaemic patients. Contrary to the impairment in CET described previously in NIDDM, the mass of CE transferred from HDL to VLDL + LDL was significantly greater in IDDM patients than in controls at 1,2, and 4 h (P less than 0.001). When the d less than 1.063 plasma fractions from IDDM subjects were combined with controls d less than 1.063 fractions, an accelerated CET response was observed which was identical to that found in intact IDDM plasma. This finding, which indicates that this disturbance in CET was associated with the acceptor lipoproteins, was confirmed when we found that it was reproduced by the addition of IDDM VLDL and not LDL to control d greater than 1.063 fractions. Changes observed in lipoprotein core lipid composition were consistent with accelerated CET occurring in IDDM in vivo: the TG/CE core lipid ratio was decreased in VLDL from six subjects (diabetic 9.5 +/- 0.8 vs control 12.9 +/- 3.4; P less than 0.1) and increased in their HDL (diabetic 0.55 +/- 0.11 vs control 0.42 +/- 0.04; P less than 0.025). No correlation was demonstrable between estimates of diabetic control (glycoalbumin, fasting glucose) and CET. These data indicate that CET may be abnormally increased in normolipidaemic IDDM patients. A defect of this type may be atherogenic because it increases the number of lipoprotein particles in plasma which resemble cholesteryl ester-enriched chylomicron and VLDL remnants but whose normal receptor-mediated catabolism may be altered.
胆固醇酯转运（CET）异常可能在糖尿病动脉血管并发症的发生发展中起作用。为了系统评估逆向胆固醇转运中的这一重要环节，我们研究了20例接受治疗、临床稳定、血脂正常的患者。与先前在非胰岛素依赖型糖尿病（NIDDM）中描述的CET受损情况相反，胰岛素依赖型糖尿病（IDDM）患者在1小时、2小时和4小时时从高密度脂蛋白（HDL）转运至极低密度脂蛋白（VLDL）+低密度脂蛋白（LDL）的胆固醇酯质量显著高于对照组（P＜0.001）。当将IDDM受试者密度小于1.063的血浆部分与对照组密度小于1.063的部分合并时，观察到CET反应加速，这与完整IDDM血浆中的情况相同。当我们发现向对照组密度大于1.063的部分添加IDDM的VLDL而非LDL可重现这一现象时，证实了这一表明CET紊乱与受体脂蛋白相关的发现。在脂蛋白核心脂质组成中观察到的变化与IDDM体内发生的CET加速一致：六名受试者的VLDL中甘油三酯/胆固醇酯（TG/CE）核心脂质比值降低（糖尿病患者为9.5±0.8，对照组为12.9±3.4；P＜0.1），而其HDL中的该比值升高（糖尿病患者为0.55±0.11，对照组为0.42±0.04；P＜0.025）。糖尿病控制指标（糖化白蛋白、空腹血糖）与CET之间未显示出相关性。这些数据表明，血脂正常的IDDM患者的CET可能异常增加。这种类型的缺陷可能具有致动脉粥样硬化性，因为它增加了血浆中类似富含胆固醇酯的乳糜微粒和VLDL残粒的脂蛋白颗粒数量，但其正常的受体介导的分解代谢可能会发生改变。
