Colhoun Helen M, Otvos James D, Rubens Mike B, Taskinen M R, Underwood S Richard, Fuller John H
Royal Free and University College London Medical School, London, UK.
Diabetes. 2002 Jun;51(6):1949-56. doi: 10.2337/diabetes.51.6.1949.
Type 1 diabetes is associated with increased coronary atherosclerosis, especially in women, even though such patients often have an apparently normal lipid profile. We examined whether lipoprotein particle sizes and subclasses differed between type 1 diabetic subjects (n = 194, age 30-55 years) and age- and sex-matched control subjects (n = 195). We examined whether any abnormalities were of similar magnitude in men and women. The relationship of particle size to electron beam computer tomography-defined coronary artery calcification, a measure of atherosclerosis, was also examined. Proton nuclear magnetic resonance (NMR) spectroscopy was used to quantify VLDL, LDL, and HDL subclass levels and average particle size on fasting samples. LDL size and subclass were similar in diabetic and nondiabetic men. In contrast, in women diabetes was associated with less large and more small LDL and a reduced LDL size (mean difference 0.2 nm; P = 0.0009). This greater effect of diabetes on LDL size in women compared with men was significant (P = 0.007). Diabetes was associated with more large and less small HDL and, to a similar degree in both sexes, a higher HDL size (difference of 0.4 nm in men and 0.3 nm in women; both P < 0.0001). There were no definitive abnormalities in VLDL size. In nondiabetic subjects, lower average HDL particle size, lower LDL size, and higher VLDL size were significantly associated with coronary calcification (P = 0.001, 0.02, and 0.04, respectively). Thus the HDL size differences with diabetes would be expected to be antiatherogenic and the LDL size differences pro-atherogenic. However, there was no clear relationship between particle size and calcification in diabetic subjects. We conclude that in the general population NMR spectroscopy-derived particle size reveals important information about the atherogenicity of lipoprotein profile. Type 1 diabetes is associated with differences in NMR-derived particle size, but their pathogenic significance is unclear.
1型糖尿病与冠状动脉粥样硬化增加有关，尤其是在女性中，尽管这类患者的血脂谱通常看似正常。我们研究了1型糖尿病患者（n = 194，年龄30 - 55岁）与年龄和性别匹配的对照受试者（n = 195）之间脂蛋白颗粒大小和亚类是否存在差异。我们还研究了男性和女性的任何异常情况是否程度相似。此外，还研究了颗粒大小与电子束计算机断层扫描定义的冠状动脉钙化（一种动脉粥样硬化的测量指标）之间的关系。采用质子核磁共振（NMR）光谱法对空腹样本中的极低密度脂蛋白（VLDL）、低密度脂蛋白（LDL）和高密度脂蛋白（HDL）亚类水平及平均颗粒大小进行定量分析。糖尿病男性和非糖尿病男性的LDL大小和亚类相似。相比之下，在女性中，糖尿病与较大LDL颗粒减少、较小LDL颗粒增多以及LDL大小减小有关（平均差异0.2纳米；P = 0.0009）。与男性相比，糖尿病对女性LDL大小的影响更大，差异具有统计学意义（P = 0.007）。糖尿病与较大HDL颗粒增多、较小HDL颗粒减少有关，且在男女两性中程度相似，HDL大小均增加（男性差异为0.4纳米，女性差异为0.3纳米；P均< 0.0001）。VLDL大小没有明确异常。在非糖尿病受试者中，较低的平均HDL颗粒大小、较低的LDL大小和较高的VLDL大小与冠状动脉钙化显著相关（分别为P = 0.001、0.02和0.04）。因此，预计糖尿病患者HDL大小的差异具有抗动脉粥样硬化作用，而LDL大小的差异具有促动脉粥样硬化作用。然而，糖尿病患者的颗粒大小与钙化之间没有明确的关系。我们得出结论，在一般人群中，NMR光谱法得出的颗粒大小揭示了有关脂蛋白谱动脉粥样硬化性的重要信息。1型糖尿病与NMR得出的颗粒大小差异有关，但其致病意义尚不清楚。
