Lewis G F, O'Meara N M, Soltys P A, Blackman J D, Iverius P H, Pugh W L, Getz G S, Polonsky K S
Department of Medicine, University of Chicago, Pritzker School of Medicine, Illinois 60637.
J Clin Endocrinol Metab. 1991 Apr;72(4):934-44. doi: 10.1210/jcem-72-4-934.
Postprandial lipoprotein metabolism may be important in atherogenesis and has not been studied in detail in noninsulin-dependent diabetes mellitus (NIDDM). We used the vitamin A fat-loading test to label triglyceride-rich lipoprotein particles of intestinal origin after ingestion of a high fat mixed meal containing 60 g fat/m2 and 60,000 U vitamin A/m2 in 12 untreated NIDDM subjects with normotriglyceridemia (NTG; triglycerides, less than 1.7 mmol/L), 7 untreated NIDDM subjects with moderate hypertriglyceridemia (HTG; triglycerides, 1.7-4.7 mmol/L), and 8 age- and weight-matched normotriglyceridemic nondiabetic controls. The postprandial triglyceride increment was greater in NIDDM with HTG (P = 0.0001) and correlated strongly in all groups with the fasting triglyceride concentration (r = 0.83; P = 0.0001). Retinyl palmitate measured in whole plasma, an Sf greater than 1000 chylomicron fraction, and an Sf less than 1000 nonchylomicron fraction was also significantly greater in NIDDM with HTG, but did not differ significantly between NIDDM with NTG and controls. In NIDDM with HTG, chylomicrons appeared to be cleared at a slower rate, as evidenced by the significantly later intersection of the chylomicron and nonchylomicron retinyl palmitate response curves (13.7 h in HTG NIDDM vs. 8.5 h in NTG NIDDM vs. 7.3 h in controls; P less than 0.01). Although fasting FFA levels were similar in all three groups, the HTG diabetic subjects had a late postprandial surge in FFAs that lasted for up to 14 h. The postprandial FFA elevation in all groups correlated with the fasting triglyceride concentration (r = 0.57; P less than 0.002) and postprandial triglyceride increment (r = 0.80; P = 0.0001). The fasting core triglyceride content of the HDL particles in NIDDM with HTG was significantly elevated compared to those in NIDDM with NTG and controls (21.0% vs. 14.0% vs. 14.1% respectively; P less than 0.05), and this increased proportionately in all groups after the meal at the expense of cholesteryl ester, the increase correlating with total plasma postprandial triglyceride increment (r = 0.51; P less than 0.01). We conclude that moderate fasting hypertriglyceridemia in NIDDM is predictive of a constellation of postprandial changes in lipids and lipoproteins that may potentiate the already unfavorable atherogenic fasting lipid profile in these subjects.
餐后脂蛋白代谢在动脉粥样硬化形成过程中可能具有重要意义，而在非胰岛素依赖型糖尿病（NIDDM）中尚未得到详细研究。我们采用维生素A脂肪负荷试验，在12名未经治疗的甘油三酯正常（NTG；甘油三酯水平低于1.7 mmol/L）的NIDDM患者、7名未经治疗的中度高甘油三酯血症（HTG；甘油三酯水平为1.7 - 4.7 mmol/L）的NIDDM患者以及8名年龄和体重匹配的甘油三酯正常的非糖尿病对照者中，让他们摄入一顿含有60 g脂肪/m²和60,000 U维生素A/m²的高脂肪混合餐，以此标记肠道来源的富含甘油三酯的脂蛋白颗粒。HTG的NIDDM患者餐后甘油三酯增量更大（P = 0.0001），且在所有组中与空腹甘油三酯浓度密切相关（r = 0.83；P = 0.0001）。在HTG的NIDDM患者中，全血中测得的棕榈酸视黄酯、Sf大于1000的乳糜微粒部分以及Sf小于1000的非乳糜微粒部分也显著更高，但NTG的NIDDM患者与对照者之间无显著差异。在HTG的NIDDM患者中，乳糜微粒的清除似乎较慢，这可通过乳糜微粒和非乳糜微粒棕榈酸视黄酯反应曲线的显著延迟相交得以证明（HTG的NIDDM患者为13.7小时，NTG的NIDDM患者为8.5小时，对照者为7.3小时；P < 0.01）。尽管所有三组的空腹游离脂肪酸（FFA）水平相似，但HTG的糖尿病患者餐后FFA出现延迟高峰，持续长达14小时。所有组餐后FFA升高与空腹甘油三酯浓度相关（r = 0.57；P < 0.002）以及餐后甘油三酯增量相关（r = 0.80；P = 0.0001）。与NTG的NIDDM患者和对照者相比，HTG的NIDDM患者中高密度脂蛋白（HDL）颗粒的空腹核心甘油三酯含量显著升高（分别为21.0%、14.0%和14.1%；P < 0.05），且餐后所有组中该比例均相应增加，同时胆固醇酯减少，这种增加与血浆餐后甘油三酯总增量相关（r = 0.51；P < 0.01）。我们得出结论，NIDDM患者中度空腹高甘油三酯血症预示着一系列餐后脂质和脂蛋白变化，这可能会增强这些患者本就不利的致动脉粥样硬化空腹脂质谱。
