Impact of the LDL subfraction phenotype on Lp-PLA2 distribution, LDL modification and HDL composition in type 2 diabetes.

BACKGROUND: Qualitative alterations of lipoproteins underlie the high incidence of atherosclerosis in diabetes. The objective of this study was to assess the impact of low-density lipoprotein (LDL) subfraction phenotype on the qualitative characteristics of LDL and high-density lipoprotein (HDL) in patients with type 2 diabetes. METHODS: One hundred twenty two patients with type 2 diabetes in poor glycemic control and 54 healthy subjects were included in the study. Patients were classified according to their LDL subfraction phenotype. Seventy-seven patients presented phenotype A whereas 45 had phenotype B. All control subjects showed phenotype A. Several forms of modified LDL, HDL composition and the activity and distribution of lipoprotein-associated phospholipase A2 (Lp-PLA2) were analyzed. RESULTS: Oxidized LDL, glycated LDL and electronegative LDL were increased in both groups of patients compared with the control group. Patients with phenotype B had increased oxidized LDL and glycated LDL concentration than patients with phenotype A. HDL composition was abnormal in patients with diabetes, being these abnormalities more marked in patients with phenotype B. Total Lp-PLA2 activity was higher in phenotype B than in phenotype A or in control subjects. The distribution of Lp-PLA2 between HDL and apoB-containing lipoproteins differed in patients with phenotype A and phenotype B, with higher activity associated to apoB-containing lipoproteins in the latter. CONCLUSIONS: The presence of LDL subfraction phenotype B is associated with increased oxidized LDL, glycated LDL and Lp-PLA2 activity associated to apoB-containing lipoproteins, as well as with abnormal HDL composition.

A cause of falsely low HDL concentrations in HIV-infected patients: increased polyclonal serum immunoglobulin.

OBJECTIVE: To describe the interference of polyclonal hypergammaglobulinemia in a direct HDL-c method. METHODS: HDL-c was measured by a direct method (Roche Diagnostics) in four HIV-infected patients showing polyclonal hypergammaglobulinemia and also by precipitation with phosphotungstic acid and ultracentrifugation at a density of 1.063 kg/L. In addition, an electrophoretic lipid profile was performed by an automated electrophoretic system. RESULTS: Direct HDL-c concentration was very low or even nondetectable in all hyperglobulinemic samples. Ultracentrifugation showed a higher HDL-c concentration, and the electrophoretic lipid profile showed a band corresponding to HDL particles whose cholesterol concentration was in concordance with that of ultracentrifugation. Kinetic monitoring of the absorbance for the direct HDL-c method showed a high reading after the first reagent addition and a final absorbance quite close to or even lower than the initial absorbance. CONCLUSION: Although interference by any HIV therapy drug cannot be completely ruled out, our results showed that when high immunoglobulin concentrations existed in the patient's serum, the direct HDL-c method yielded low or undetectable HDL-c values. The high initial absorbance observed suggested an interaction between immunoglobulins and the first reagent of the method, producing a complex that scattered light and falsely decreased HDL-c concentrations.