Effect of type 2 diabetes on various electrophoretic characteristics of low-density lipoprotein particles in women

Abstract

Aims/hypothesis. Coronary heart disease represents the leading cause of death in type 2 diabetic patients. As the small, dense LDL phenotype is a typical feature of the dyslipidaemic state found in type 2 diabetes, this characteristic could be an important mediator of the elevated coronary heart disease risk in this condition. We have therefore studied the effect of type 2 diabetes on various electrophoretic characteristics of LDL particles. Methods. Potential differences in LDL peak particle size and in concentration of LDL cholesterol in small (<255 Å) and large (>260 Å) LDL particles were assessed by polyacrylamide gradient gel electrophoresis among 183 non-diabetic and 56 type 2 diabetic women. Results. LDL peak particle size was significantly smaller in type 2 diabetic women than in non-diabetic women (p<0.0001). In addition, the proportion of small LDL particles (<255 Å) was higher in type 2 diabetic women, whereas the proportion of large LDL particles (>260 Å) was lower than in non-diabetic women (p<0.0002). Type 2 diabetic women also had the highest waist circumference and triglyceride levels (p<0.03). When subgroups of non-diabetic and type 2 diabetic women were individually matched (n=41) for similar waist circumference and triglyceride levels, the differences initially found in LDL peak particle size and in the proportion of small and large LDL particles remained significantly different between the two groups (p<0.01). Conclusions/interpretation. These results provide evidence that type 2 diabetes may have an independent effect on LDL peak particle size and on the proportion of small and large LDL particles.

Polyacrylamide Gradient Gel Electrophoresis of Lipoprotein Subclasses

“…Plasma cholesterol concentrations of LDL subclasses have been approximated by multiplying the percent areas of Sudan black-stained gels by plasma LDL cholesterol [119,129]. Based on published [130][131][132] and personal observations, Rainwater and colleagues [133] argue that when the gels are stained with Sudan black, absorbance profiles reflect the cholesterol distribution among LDL subclasses.…”

“…Haffner and colleagues [188] reported that men and women who had NIDDM had smaller LDL peak diameter than those who were nondiabetic, but when adjusted for triglycerides and HDL cholesterol concentrations, the difference persisted in women but not men. Blackburn and colleagues [129] also reported that LDL peak particle size was significantly smaller in women who had type 2 diabetes mellitus than in women who were nondiabetic, even when matched for waist circumferences and plasma triglyceride levels, and those who had diabetes had a greater proportion of their LDL cholesterol in small LDL (!25.5 nm) and a smaller proportion in large LDL (R26.0 nm) than women who did not have diabetes, despite no differences in total LDL cholesterol.…”

Small dense low-density lipoprotein and its role as an independent predictor of cardiovascular disease

“…Recently, however, evidence has emerged that other metabolic disturbances may also predispose to this pattern. Blackburn et al [27] found a lower LDL peak particle size in women with diabetes compared with control subjects even when differences in waist and plasma triglyceride were taken into account. Similarly, Veerkamp et al [28] found that subjects with familial combined hyperlipidaemia had increased levels of apolipoprotein B and more small dense LDL independent of the presence of insulin resistance and the degree of obesity.…”

Circulating IGFBP-2 levels are incrementally linked to correlates of the metabolic syndrome and independently associated with VLDL triglycerides

“…The LDL peak particle diameter was obtained from nondenaturing 2e16% polyacrylamide gradient gel electrophoresis as previously described [30]. LDL particle size was extrapolated from the relative migration of four plasma standards of known diameters.…”