Hirano T, Oi K, Sakai S, Kashiwazaki K, Adachi M, Yoshino G
First Department of Internal Medicine, Showa University School of Medicine, Tokyo, Japan.
Atherosclerosis. 1998 Nov;141(1):77-85. doi: 10.1016/s0021-9150(98)00150-6.
To determine whether high prevalence of small dense low-density lipoprotein (LDL) in non-insulin-dependent diabetes (NIDDM) with nephropathy is directly associated with kidney damage, we measured LDL particle size by non-denaturing 2-16% gradient polyacrylamide gel electrophoresis in non-diabetic patients with primary renal disease and compared the results to particle size in NIDDM patients with diabetic nephropathy. The average LDL particle diameter was significantly smaller in patients with diabetic nephropathy (245+/-3 A mean +/- SEM) compared to the controls (263+/-1 A), diabetics without nephropathy (257+/-2 A), patients with primary renal disease (254+/-2 A) or non-diabetic patients treated with hemodialysis (HD) (260+/-1 A). The incidence of small LDL (mean diameter is < or =255 A) was remarkably increased in diabetic nephropathy (67%) compared to diabetes without nephropathy (27%), patients with renal disease (24%), HD patients (15%) and controls (10%). LDL size in patients with primary renal disease was significantly smaller than those in controls. However, because there was an excellent correlation between LDL size and plasma triglyceride (TG) levels, when hypertriglyceridemic subjects (TG >1.7 mM) were excluded, no difference of LDL size was observed between the renal disease group (260+/-2 A) and the control group (264+/-1 A). On the other hand, even when hypertriglyceridemic subjects were excluded, LDL size was still smaller in diabetic nephropathy (250+/-4 A). We performed an oral fat load test in normotriglyceridemic subjects (fasting TG <1.7 mM) of control, diabetes with and without nephropathy and primary renal disease. The TG responses in plasma and TG-rich-lipoprotein (TRL) (d <1.006) after the oral fat load were significantly greater in NIDDMs with nephropathy compared to controls or NIDDMs without nephropathy, while such a marked postprandial lipemia was not observed in patients with primary renal disease. In these fasting normotriglyceridemic subjects, LDL size was significantly inversely correlated with postprandial TG responses, which is totally independent from fasting TG levels. These results suggest that high prevalence of small dense LDL in NIDDM patients with nephropathy is not directly associated with kidney damage. Postprandial lipemia may play an important role in reducing LDL particle size in these patients.
为了确定非胰岛素依赖型糖尿病（NIDDM）合并肾病患者中，小而密低密度脂蛋白（LDL）的高患病率是否与肾脏损害直接相关，我们采用非变性2 - 16%梯度聚丙烯酰胺凝胶电泳法，对原发性肾病的非糖尿病患者测量LDL颗粒大小，并将结果与NIDDM合并糖尿病肾病患者的颗粒大小进行比较。与对照组（263±1 Å）、无肾病的糖尿病患者（257±2 Å）、原发性肾病患者（254±2 Å）或接受血液透析（HD）的非糖尿病患者（260±1 Å）相比，糖尿病肾病患者的平均LDL颗粒直径显著更小（245±3 Å，平均值±标准误）。糖尿病肾病患者中小LDL（平均直径≤255 Å）的发生率（67%）显著高于无肾病的糖尿病患者（27%）、肾病患者（24%）、HD患者（15%）和对照组（10%）。原发性肾病患者的LDL大小显著小于对照组。然而，由于LDL大小与血浆甘油三酯（TG）水平之间存在良好的相关性，当排除高甘油三酯血症患者（TG＞1.7 mM）后，肾病组（260±2 Å）和对照组（264±1 Å）之间未观察到LDL大小的差异。另一方面，即使排除高甘油三酯血症患者，糖尿病肾病患者的LDL大小仍然较小（250±4 Å）。我们对对照组、有或无肾病的糖尿病患者以及原发性肾病患者中的正常甘油三酯血症受试者（空腹TG＜1.7 mM）进行了口服脂肪负荷试验。与对照组或无肾病的NIDDM患者相比，合并肾病的NIDDM患者口服脂肪负荷后血浆和富含甘油三酯脂蛋白（TRL）（d＜1.006）中的TG反应显著更大，而原发性肾病患者未观察到如此明显的餐后血脂异常。在这些空腹正常甘油三酯血症受试者中，LDL大小与餐后TG反应显著负相关，这与空腹TG水平完全无关。这些结果表明，NIDDM合并肾病患者中小而密LDL的高患病率与肾脏损害无直接关联。餐后血脂异常可能在降低这些患者的LDL颗粒大小中起重要作用。
