Bioletto S, Golay A, Munger R, Kalix B, James R W
Clinical Diabetes Unit, Division of Endocrinology and Diabetology, and the Division for Treatment of Chronic Diseases, University Hospital, Geneva, Switzerland.
Am J Clin Nutr. 2000 Feb;71(2):443-9. doi: 10.1093/ajcn/71.2.443.
The influence of hyperinsulinemia on concentrations of lipoprotein subfractions in obese, nondiabetic persons has not been clarified.
We analyzed VLDL and LDL subfractions before and after a euglycemic, hyperinsulinemic clamp.
Lipoprotein subfractions were isolated from plasma samples obtained in the basal state and after a 4-h clamp from obese patients, obese patients with type 2 diabetes, and nonobese control subjects.
Hyperinsulinemia tended to reduce concentrations (&xmacr;: 20%) of large, triacylglycerol-rich VLDL(1) in obese patients but had a minor effect on VLDL(2) and VLDL(3). Placing obese patients into insulin-sensitive and insulin-resistant subgroups revealed distinct effects of the degree of insulin sensitivity on VLDL. VLDL(1) concentrations decreased by a mean of 38% (P < 0.05) in insulin-sensitive patients after the clamp, similar to but less marked than the decrease observed in control subjects (&xmacr;: 62%; P < 0.01). VLDL(1) concentrations did not change significantly after the clamp in insulin-resistant patients (and patients with type 2 diabetes), whereas VLDL(3) concentrations decreased in both groups, in contrast with the changes seen in the insulin-sensitive patients and control subjects. Acute hyperinsulinemia modified the LDL subfraction profile toward a greater prevalence of small, dense LDLs in insulin-resistant patients and patients with type 2 diabetes.
Insulin resistance appears to be the primary determinant of the modifications to VLDL subfraction concentrations. Our results suggest a continuum of impaired insulin action on VLDL, ranging from that in healthy persons to that in patients with type 2 diabetes, in which obese patients occupy a transition state. Insulin resistance may also play a role in detrimental modifications to the LDL profile by allowing the development of hypertriglyceridemia.
高胰岛素血症对肥胖非糖尿病患者脂蛋白亚组分浓度的影响尚未明确。
我们分析了正常血糖高胰岛素钳夹前后的极低密度脂蛋白（VLDL）和低密度脂蛋白（LDL）亚组分。
从肥胖患者、2型糖尿病肥胖患者和非肥胖对照受试者的基础状态血浆样本以及4小时钳夹后血浆样本中分离脂蛋白亚组分。
高胰岛素血症倾向于降低肥胖患者中富含三酰甘油的大颗粒VLDL(1)的浓度（均值：20%），但对VLDL(2)和VLDL(3)影响较小。将肥胖患者分为胰岛素敏感和胰岛素抵抗亚组后发现，胰岛素敏感性程度对VLDL有不同影响。钳夹后，胰岛素敏感患者的VLDL(1)浓度平均下降38%（P<0.05），与对照受试者观察到的下降相似但程度较轻（均值：62%；P<0.01）。胰岛素抵抗患者（和2型糖尿病患者）钳夹后VLDL(1)浓度无显著变化，而两组的VLDL(3)浓度均下降，这与胰岛素敏感患者和对照受试者的变化相反。急性高胰岛素血症使胰岛素抵抗患者和2型糖尿病患者的LDL亚组分谱向小而密LDL的更高患病率转变。
胰岛素抵抗似乎是VLDL亚组分浓度改变的主要决定因素。我们的结果表明，胰岛素对VLDL作用受损存在一个连续过程，从健康人到2型糖尿病患者，肥胖患者处于过渡状态。胰岛素抵抗还可能通过导致高甘油三酯血症的发生，在LDL谱的有害改变中起作用。
