Lipoprotein subclasses and particle sizes and their relationship with coronary artery calcification in men and women with and without type 1 diabetes

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.