胰岛素治疗可诱导非胰岛素依赖型糖尿病患者血清脂蛋白发生抗动脉粥样硬化改变。

Insulin therapy induces antiatherogenic changes of serum lipoproteins in noninsulin-dependent diabetes.

作者信息

Taskinen M R, Kuusi T, Helve E, Nikkilä E A, Yki-Järvinen H

机构信息

Second Department of Medicine, University of Helsinki, Finland.

出版信息

Arteriosclerosis. 1988 Mar-Apr;8(2):168-77. doi: 10.1161/01.atv.8.2.168.

DOI:10.1161/01.atv.8.2.168

PMID:3279941

Abstract

To study the effects of rigorous insulin therapy on serum lipoproteins in patients with noninsulin-dependent diabetes not controlled with oral agents only, we measured serum lipoproteins, apoproteins, lipolytic enzymes, and glucose disposal using an insulin clamp technique before and after 4 weeks of insulin therapy. Lipoproteins were isolated by ultracentrifugation and high density lipoprotein (HDL) subfractions, by rate-zonal density gradient ultracentrifugation. The group included 11 women and eight men (age 58 +/- 1 years and RBW 125 +/- 4%). Body weight, glycosylated hemoglobin, mean diurnal glucose, plasma free insulin, and glucose uptake (M-value) were 75 vs. 76 kg; 11.9 vs. 8.9%; 234 vs. 124 mg/dl; 12 vs. 27 microU/ml; and 5.0 +/- 0.4 vs. 7.1 +/- 0.6 mg/kg/min before and after insulin therapy, respectively. After insulin therapy there was a decrease of very low density lipoprotein (VLDL) triglyceride (-60%, p less than 0.001) but an increase of HDL2 cholesterol (+21%, p less than 0.001); HDL2 phospholipids (+38%, p less than 0.001); HDL2 proteins (+23%, p less than 0.01); and HDL2 mass (127 +/- 11 vs. 158 +/- 12 mg/dl, p less than 0.001). There was a decrease of HDL3 cholesterol (-13%, p less than 0.05); HDL3 phospholipids (-16%, p less than 0.05); HDL3 proteins (-18%, p less than 0.001); and HDL3 mass (179 +/- 6 vs. 146 +/- 6, p less than 0.01). Zonal profiles showed a redistribution of particles from HDL3 to HDL2. Serum apo A-I increased (p less than 0.05), apo A-II remained constant, but apo B decreased (-29%, p less than 0.001). The most marked change during insulin therapy was a 2.3-fold increase in adipose tissue lipoprotein lipase (LPL) activity (p less than 0.001). The changes of VLDL and HDL subfractions were not explained by respective changes of the blood glucose, free insulin, or M-value. The data indicate that intensive insulin therapy induces antiatherogenic changes in serum lipids and lipoproteins and suggest that the induction of LPL by insulin is the major factor responsible for redistribution of HDL particles from HDL3 to HDL2.

摘要

为研究强化胰岛素治疗对仅用口服药物无法控制的非胰岛素依赖型糖尿病患者血清脂蛋白的影响，我们在胰岛素治疗4周前后，采用胰岛素钳夹技术测定了血清脂蛋白、载脂蛋白、脂解酶及葡萄糖处置情况。脂蛋白通过超速离心法分离，高密度脂蛋白（HDL）亚组分则通过速率区带密度梯度超速离心法分离。该组包括11名女性和8名男性（年龄58±1岁，相对体重125±4%）。胰岛素治疗前后，体重、糖化血红蛋白、平均日间血糖、血浆游离胰岛素及葡萄糖摄取量（M值）分别为75 vs. 76 kg；11.9 vs. 8.9%；234 vs. 124 mg/dl；12 vs. 27 μU/ml；以及5.0±0.4 vs. 7.1±0.6 mg/kg/min。胰岛素治疗后，极低密度脂蛋白（VLDL）甘油三酯降低（-60%，p<0.001），但HDL2胆固醇升高（+21%，p<0.001）；HDL2磷脂升高（+38%，p<0.001）；HDL2蛋白升高（+23%，p<0.01）；HDL2质量升高（127±11 vs. 158±12 mg/dl，p<0.001）。HDL3胆固醇降低（-13%，p<0.05）；HDL3磷脂降低（-16%，p<0.05）；HDL3蛋白降低（-18%，p<0.001）；HDL3质量降低（179±6 vs. 146±6，p<0.01）。区带图谱显示颗粒从HDL3重新分布至HDL2。血清载脂蛋白A-I升高（p<0.05），载脂蛋白A-II保持不变，但载脂蛋白B降低（-29%，p<0.001）。胰岛素治疗期间最显著的变化是脂肪组织脂蛋白脂肪酶（LPL）活性增加2.3倍（p<0.001）。VLDL和HDL亚组分的变化无法用血糖、游离胰岛素或M值的相应变化来解释。数据表明强化胰岛素治疗可诱导血清脂质和脂蛋白发生抗动脉粥样硬化变化，并提示胰岛素诱导LPL是HDL颗粒从HDL3重新分布至HDL2的主要因素。