Sánchez-Quesada J L, Pérez A, Caixàs A, Ordónmez-Llanos J, Carreras G, Payés A, González-Sastre F, de Leiva A
Department of Biochemistry, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain.
Diabetologia. 1996 Dec;39(12):1469-76. doi: 10.1007/s001250050600.
We evaluated the effect of improving glycaemic control with intensive insulin therapy on LDL susceptibility to oxidation, electronegative LDL proportion, and LDL subfraction phenotype in a group of 25 patients with short-duration insulin-dependent diabetes mellitus (IDDM); 25 matched healthy control subjects were also studied. LDL susceptibility to oxidation was measured by continuous monitoring of conjugated diene formation. Electronegative LDL was isolated by anion exchange chromatography, and quantified as percentage of total LDL. Six LDL subfractions were isolated by density gradient ultracentrifugation and phenotype A or B classified as the quotient (LDL1-LDL3)/(LDL4-LDL6). Compared to the control group, IDDM subjects with poor glycaemic control showed higher electronegative LDL (19.03 +/- 10.09 vs 9.59 +/- 2.98%, p < 0.001), similar LDL subfraction phenotype and lower susceptibility to oxidation (lag phase 45.6 +/- 8.8 vs 41.2 +/- 4.7 min, p < 0.05). After three months of intensive insulin therapy, HbA1c decreased from 10.88 +/- 2.43 to 5.69 +/- 1.54% (p < 0.001), and electronegative LDL to 13.84 +/- 5.15% (p < 0.05). No changes in LDL susceptibility to oxidation or LDL subfraction phenotype were observed. Electronegative LDL appeared significantly correlated to HbA1c and fructosamine (p < 0.01 and p < 0.001) only in poorly controlled IDDM patients. These findings suggest that high electronegative LDL in IDDM subjects is related to the degree of glycaemic control, and could therefore be due to LDL glycation rather than to LDL oxidation or changes in LDL subfraction phenotype.
我们评估了强化胰岛素治疗改善血糖控制对25例短期胰岛素依赖型糖尿病（IDDM）患者低密度脂蛋白（LDL）氧化易感性、负电LDL比例和LDL亚组分表型的影响；同时研究了25例匹配的健康对照者。通过连续监测共轭二烯的形成来测定LDL的氧化易感性。通过阴离子交换色谱法分离负电LDL，并将其定量为总LDL的百分比。通过密度梯度超速离心法分离出六个LDL亚组分，并将A或B表型分类为（LDL1-LDL3）/（LDL4-LDL6）的商。与对照组相比，血糖控制不佳的IDDM患者显示出更高的负电LDL（19.03±10.09 vs 9.59±2.98%，p<0.001）、相似的LDL亚组分表型和更低的氧化易感性（延迟期45.6±8.8 vs 41.2±4.7分钟，p<0.05）。强化胰岛素治疗三个月后，糖化血红蛋白（HbA1c）从10.88±2.43降至5.69±1.54%（p<0.001），负电LDL降至13.84±5.15%（p<0.05）。未观察到LDL氧化易感性或LDL亚组分表型的变化。仅在血糖控制不佳的IDDM患者中，负电LDL与HbA1c和果糖胺显著相关（p<0.01和p<0.001）。这些发现表明，IDDM患者中高负电LDL与血糖控制程度有关，因此可能是由于LDL糖基化而非LDL氧化或LDL亚组分表型的改变。
