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Relationships between cholesterol efflux and high-density lipoprotein particles in patients with type 2 diabetes mellitus
High-density lipoprotein (HDL) encompasses a heterogeneous population of lipoproteins with differences in functionality. The impact of HDL heterogeneity on its ability to support HDL-mediated cholesterol efflux has not been previously studied in patients with type 2 diabetes mellitus (T2DM).
To examine the relationships between various HDL subtypes and cholesterol efflux from macrophages in patients with T2DM.
Lipoprotein molecular profiles of 44 patients were studied by NMR spectroscopy. Cholesterol efflux was expressed as percentage efflux of radioactivity from lipid-laden THP-1 macrophages preincubated with 3H-cholesterol and then incubated with serum depleted of apolipoprotein B to provide an HDL-enriched acceptor medium.
There was a predominance of small HDL particles (59%) and small putatively atherogenic low-density lipoprotein particles (56%). Neither HDL-C nor ApoA-I concentrations showed statistically significant correlations with percentage cholesterol efflux, but a significant positive relationship was found with the total HDL particle concentration (r = 0.41, P = .005) contributed to largely by medium HDL particles (r = 0.41, P = .006). The correlation between medium-sized HDL particle concentration remained significantly associated with cholesterol efflux when assessed with the use of a linear regression model that included all the HDL lipoprotein subclass concentrations as well as apolipoprotein A-I. Importantly, no statistically significant association was observed between the number of small HDL particles and cholesterol efflux. Hemoglobin A1c showed a significant inverse correlation with cholesterol efflux (r = −0.31, P = .04).
In patients with moderately controlled type 2 diabetes mellitus, cholesterol efflux from macrophages incubated with apolipoprotein B–depleted plasmas correlated significantly and positively with the concentration of total and medium-sized HDL and not with that of the smallest particles.