Tan K C, Cooper M B, Ling K L, Griffin B A, Freeman D J, Packard C J, Shepherd J, Hales C N, Betteridge D J
Department of Medicine, University College London Medical School, Sir Jules Thorn Institute, Middlesex Hospital, UK.
Atherosclerosis. 1995 Mar;113(2):273-87. doi: 10.1016/0021-9150(94)05454-q.
We have studied low density lipoprotein (LDL) subclass distribution in a group of male patients with non-insulin-dependent diabetes mellitus (NIDDM) and investigated its relationships to fasting and postprandial triglyceride (TG)-rich lipoproteins, insulin resistance, lipoprotein lipase (EC 3.1.1.3; LPL), hepatic lipase (EC 3.1.1.34; HL), lecithin:cholesterol acyl transferase (EC 2.3.1.43; LCAT) and cholesteryl ester transfer protein (CETP) activities. LDL was subfractionated by density gradient ultracentrifugation. Postprandial lipoproteins were measured after an oral fat load using retinyl palmitate as a marker for intestinal TG-rich lipoproteins. Hypertriglyceridaemic NIDDMs (HTG) had a preponderance of small dense LDL particles present in the plasma and reduced amounts of large buoyant species when compared to normotriglyceridaemic patients (NTG) and controls. Both groups of diabetics were more insulin resistant than the controls (P < 0.05) and had raised concentrations of proinsulin (P < 0.05), although insulin content did not differ significantly. 32-33 split proinsulin (SPI) was the major insulin-like molecule present in HTG and was present in significantly higher amounts in these patients (P < 0.05) than either NTG or control subjects and correlated significantly with the presence of small dense LDL particles. After a test meal, the postprandial chylomicron response was greater in HTG than either NTG diabetics or controls (P < 0.05). Chylomicron remnants were present to a greater extent in HTG than in NTG and controls (P < 0.05), although in this case NTG also contained more chylomicron remnants than control subjects (P < 0.05). There was no difference in the LPL activity, CETP and LCAT between diabetics and controls, whereas an increase in hepatic lipase activity was seen in the HTG diabetics (P < 0.05). Both CETP and LCAT activities increased postprandially. Multivariate analysis showed that TG, HDL content and HL activity were the most important determinants of small dense LDL concentration in the fasting state (R2 = 67%). Postprandially, chylomicron remnant clearance, HL and insulin resistance were the major determinants (R2 = 61%) of LDL-III.
我们研究了一组非胰岛素依赖型糖尿病（NIDDM）男性患者的低密度脂蛋白（LDL）亚类分布，并调查了其与空腹及餐后富含甘油三酯（TG）的脂蛋白、胰岛素抵抗、脂蛋白脂肪酶（EC 3.1.1.3；LPL）、肝脂肪酶（EC 3.1.1.34；HL）、卵磷脂胆固醇酰基转移酶（EC 2.3.1.43；LCAT）及胆固醇酯转运蛋白（CETP）活性之间的关系。通过密度梯度超速离心法对LDL进行亚组分分离。口服脂肪负荷后，使用棕榈酸视黄酯作为肠道富含TG脂蛋白的标志物来测量餐后脂蛋白。与正常甘油三酯血症患者（NTG）及对照组相比，高甘油三酯血症NIDDM患者（HTG）血浆中存在大量小而密的LDL颗粒，而大的漂浮型LDL颗粒数量减少。两组糖尿病患者均比对照组更具胰岛素抵抗（P < 0.05），且胰岛素原浓度升高（P < 0.05），尽管胰岛素含量无显著差异。32 - 33裂解胰岛素原（SPI）是HTG中主要的胰岛素样分子，这些患者体内的SPI含量显著高于NTG患者或对照组（P < 0.05），且与小而密的LDL颗粒的存在显著相关。试验餐后，HTG患者的餐后乳糜微粒反应比NTG糖尿病患者或对照组更强（P < 0.05）。与NTG及对照组相比，HTG患者体内乳糜微粒残粒的含量更高（P < 0.05），不过在这种情况下，NTG患者体内的乳糜微粒残粒也比对照组更多（P < 0.05）。糖尿病患者与对照组之间的LPL活性、CETP及LCAT无差异，而HTG糖尿病患者的肝脂肪酶活性升高（P < 0.05）。CETP及LCAT活性在餐后均升高。多变量分析显示，空腹状态下，TG、HDL含量及HL活性是小而密LDL浓度的最重要决定因素（R2 = 67%）。餐后，乳糜微粒残粒清除率、HL及胰岛素抵抗是LDL-III的主要决定因素（R2 = 61%）。
