Lipoprotein Subclasses and Particle Sizes and Their Relationship With Coronary Artery Calcification in Men and Women With and Without Type 1 Diabetes
- Helen M. Colhoun1,
- James D. Otvos2,
- Mike B. Rubens3,
- M. R. Taskinen4,
- S. Richard Underwood3 and
- John H. Fuller1
- 1Royal Free and University College London Medical School, London, U.K
- 2LipoMed Inc., Raleigh, North Carolina
- 3Royal Brompton and Harefield NHS Hospital Trust, London, U.K
- 4University of Helsinki, Helsinki, Finland
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 2effect 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.
Address correspondence and reprint requests to Helen M. Colhoun, EURODIAB, Department of Epidemiology and Public Health, University College London Medical School, 1-19 Torrington Place, London WC1E 6BT, U.K. E-mail:.
J.D.O. is employed by, serves on the board of directors of, and holds stock in LipoMed Inc.
Received for publication 3 July 2001 and accepted in revised form 26 February 2002.
CAC, coronary artery calcification; CHD, coronary heart disease; CT, computed tomography; CV, coefficient of variation; DCCT, Diabetes Control and Complications Trial; ECG, electrocardiogram; EDIC, Epidemiology of Diabetes Interventions and Complications; HRT, hormone replacement therapy; IDL, intermediate-density lipoprotein; NMR, nuclear magnetic resonance; OR, odds ratio.