Lipoprotein Subclasses and Particle Sizes and Their Relationship With Coronary Artery Calcification in Men and Women With and Without Type 1 Diabetes

• Published in: Diabetes (New York, N.Y.) Vol. 51; no. 6; pp. 1949 - 1956
• Main Authors: COLHOUN, Helen M, OTVOS, James D, RUBENS, Mike B, TASKINEN, M. R, UNDERWOOD, S. Richard, FULLER, John H
• Format: Journal Article
• Language: English
• Published: Alexandria, VA American Diabetes Association 01-06-2002
• Subjects: Adult; Arteries; Associated diseases and complications; Biological and medical sciences; Calcification; Calcification (Physiology); Calcinosis - blood; Coronary Artery Disease - blood; Coronary heart disease; Diabetes Mellitus, Type 1 - blood; Diabetes Mellitus, Type 1 - complications; Diabetes. Impaired glucose tolerance; Endocrine pancreas. Apud cells (diseases); Endocrinopathies; Female; Health aspects; Humans; Lipoproteins - blood; Lipoproteins, HDL - blood; Lipoproteins, IDL; Lipoproteins, LDL - blood; Lipoproteins, VLDL - blood; Magnetic Resonance Spectroscopy; Male; Medical sciences; Middle Aged; Particle Size; Risk Factors; Sex Characteristics; Type 1 diabetes; United Kingdom; Finland; Endocrinopathy; Human; Immunopathology; Particle size; Coronary artery; Cardiovascular disease; Autoimmune disease; Lipoprotein; Vascular disease; Atherosclerosis; Calcification; Insulin dependent diabetes; Complication
• ISSN: 0012-1797; 1939-327X
• DOI: 10.2337/diabetes.51.6.1949

Lipoprotein Subclasses and Particle Sizes and Their Relationship With Coronary Artery Calcification in Men and Women With
and Without Type 1 Diabetes
Helen M. Colhoun 1 ,
James D. Otvos 2 ,
Mike B. Rubens 3 ,
M. R. Taskinen 4 ,
S. Richard Underwood 3 and
John H. Fuller 1
1 Royal Free and University College London Medical School, London, U.K
2 LipoMed Inc., Raleigh, North Carolina
3 Royal Brompton and Harefield NHS Hospital Trust, London, U.K
4 University of Helsinki, Helsinki, Finland
Abstract
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.
Footnotes
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: h.colhoun{at}public-health.ucl.ac.uk .
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.
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