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Simvastatin and bezafibrate increase cholesterol efflux in men with type 2 diabetes
Author(s) -
Triolo Michela,
Annema Wijtske,
Boer Jan Freark,
Tietge Uwe J. F.,
Dullaart Robin P. F.
Publication year - 2014
Publication title -
european journal of clinical investigation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.164
H-Index - 107
eISSN - 1365-2362
pISSN - 0014-2972
DOI - 10.1111/eci.12226
Subject(s) - bezafibrate , simvastatin , type 2 diabetes , medicine , efflux , endocrinology , cholesterol , hydroxymethylglutaryl coa reductase inhibitors , diabetes mellitus , pharmacology , chemistry , biochemistry
Background The importance of functional properties of high‐density lipoproteins ( HDL ) for atheroprotection is increasingly recognized. We determined the impact of lipid‐lowering therapy on 3 key HDL functionalities in Type 2 diabetes mellitus (T2 DM ). Materials and methods A placebo‐controlled, randomized cross‐over study (three 8‐week treatment periods with simvastatin (40 mg daily), bezafibrate (400 mg daily), alone and in combination) was carried out in 14 men with T2 DM . Cholesterol efflux was determined using human THP ‐1 monocyte‐derived macrophages, HDL antioxidative capacity was measured as inhibition of low‐density lipoprotein oxidation in vitro , and HDL anti‐inflammatory capacity was assessed as suppression of thrombin‐induced monocyte chemotactic protein 1 expression in human umbilical vein endothelial cells. Pre‐β‐ HDL was assayed using crossed immunoelectrophoresis. Results While cholesterol efflux increased in response to simvatatin, bezafibrate and combination treatment (+12 to +23%; anova , P = 0·001), HDL antioxidative capacity ( P = 0·23) and HDL anti‐inflammatory capacity ( P = 0·15) did not change significantly. Averaged changes in cellular cholesterol efflux during active treatment were correlated positively with changes in HDL cholesterol, apoA‐I and pre‐β‐ HDL ( P < 0·05 to P < 0·001). There were no inter‐relationships between changes in the three HDL functionalities during treatment ( P > 0·10). Changes in HDL antioxidative capacity and anti‐inflammatory capacity were also unrelated to changes in HDL cholesterol and apoA‐I, while changes in HDL antioxidative capacity were related inversely to pre‐β‐ HDL ( P < 0·05). Conclusion Simvastatin and bezafibrate increase cholesterol efflux, parallel to HDL cholesterol and apoA‐I responses. The antioxidative and anti‐inflammatory properties of HDL are not to an important extent affected by these therapeutic interventions.