EFFECT OF DIABETES ON LIPOPROTEIN SIZE

The effects of diabetes on lipoprotein particle sizes were assessed us ing samples from 94 subjects with non-insulin-dependent diabetes melli tus. From a larger population of nondiabetic subjects who showed norma l glucose tolerance, we selected an exact match in terms of age, sex, and menopausal status. We designed a protocol to make nondenaturing gr adient gels for the resolution of LDL subfractions and generated two m easures of LDL size: diameter of the predominant LDL species and propo rtion of LDL cholesterol (LDL-C) in particles larger than 25.5 nm (lar ge LDL-C). Similarly, we made two measures of HDL size, large HDL chol esterol (HDL-C) and large HDL-apoAI, which represent the proportion of HDL-C and apoAI, respectively, occurring on particles larger than HDL (3). In pairwise comparisons, diabetes was associated with significant ly (P < .004) smaller lipoprotein particles for all measures except la rge HDL-C. Each of the size measures was significantly and positively correlated with each of the others, suggesting that common metabolic m echanisms influence lipoprotein particle sizes across classes of lipop roteins. In addition, each of the size measures was correlated with a variety of measures of HDL and beta-lipoprotein concentrations, which included HDL-C, LDL-C, triglycerides, and apoAI, apoB, and apoE. We us ed stepwise regression analyses to select from the measures of lipopro tein concentrations those independently correlated with each of the li poprotein size measures. After adjusting for these metabolic correlate s of lipoprotein size measures, we found the effect of diabetes on lip oprotein size measures was no longer significant except for a modest e ffect (P = .027) on large HDL-apoAI. These results suggest that diabet es alters aspects of lipoprotein metabolism that result in modificatio n of lipoprotein particle sizes.