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From the Department of Genetics, Southwest Foundation for Biomedical Research, and the Division of Clinical Epidemiology (S.M.H.), Department of Medicine, University of Texas Health Science Center, San Antonio, Tex.
Correspondence to David L. Rainwater, PhD, Department of Genetics, Southwest Foundation for Biomedical Research, PO Box 28147, San Antonio, TX 78228-0147.
Abstract The effects of diabetes on lipoprotein particle sizes were assessed using samples from 94 subjects with noninsulin-dependent diabetes mellitus. From a larger population of nondiabetic subjects who showed normal glucose tolerance, we selected an exact match in terms of age, sex, and menopausal status. We designed a protocol to make nondenaturing gradient gels for the resolution of LDL subfractions and generated two measures of LDL size: diameter of the predominant LDL species and proportion of LDL cholesterol (LDL-C) in particles larger than 25.5 nm (large LDL-C). Similarly, we made two measures of HDL size, large HDL cholesterol (HDL-C) and large HDLapoAI, which represent the proportion of HDL-C and apoAI, respectively, occurring on particles larger than HDL3. In pairwise comparisons, diabetes was associated with significantly (P<.004) smaller lipoprotein particles for all measures except large HDL-C. Each of the size measures was significantly and positively correlated with each of the others, suggesting that common metabolic mechanisms influence lipoprotein particle sizes across classes of lipoproteins. In addition, each of the size measures was correlated with a variety of measures of HDL and ß-lipoprotein concentrations, which included HDL-C, LDL-C, triglycerides, and apoAI, apoB, and apoE. We used stepwise regression analyses to select from the measures of lipoprotein concentrations those independently correlated with each of the lipoprotein size measures. After adjusting for these metabolic correlates of lipoprotein size measures, we found the effect of diabetes on lipoprotein size measures was no longer significant except for a modest effect (P=.027) on large HDLapoAI. These results suggest that diabetes alters aspects of lipoprotein metabolism that result in modification of lipoprotein particle sizes.
Key Words: electrophoresis lipoproteins, low-density apolipoproteins lipoproteins, high-density diabetes
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