No improvement of high-density lipoprotein (HDL) vasorelaxant effect despite increase in HDL cholesterol concentration in type 2 diabetic patients treated with glitazones.
Fiche publication
Date publication
octobre 2014
Auteurs
Membres identifiés du Cancéropôle Est :
Pr PETIT Jean-Michel, Pr VERGES Bruno
Tous les auteurs :
Persegol L, Duvillard L, Monier S, Brindisi MC, Bouillet B, Petit JM, Verges B
Lien Pubmed
Résumé
CONTEXT: High-density lipoproteins (HDLs) from type 2 diabetic patients are unable to counteract the inhibitory effect of oxidized low-density lipoproteins (ox-LDLs) on vasorelaxation. We hypothesized that glitazones, which improve glycemic control and dyslipidemia, could correct this abnormality. OBJECTIVES AND DESIGN: We compared the ability of HDL from controls (n = 12) and from type 2 diabetic patients before and after 6 months of treatment with either rosiglitazone (n = 11) or pioglitazone (n = 8) to counteract the inhibitory effect of ox-LDL on vasodilatation of rabbit aorta rings. RESULTS: Rosiglitazone induced a decrease in hemoglobin A1c (7.7% +/- 1.1% vs 9.8% +/- 1.0%, P = .003) and an increase in HDL cholesterol (1.14 +/- 0.32 vs 0.98 +/- 0.24 mmol/L, P = .033). Pioglitazone induced a decrease in hemoglobin A1c (8.3% +/- 2.5% vs 9.5% +/- 3.2%, P = .068) and serum triglycerides (1.58 +/- 0.89 vs 2.03 +/- 0.70 mmol/L, P = .069) and an increase in HDL cholesterol (1.39 +/- 0.22 vs 1.14 +/- 0.22 mmol/L, P = .018). The triglyceride content of HDL was unchanged by rosiglitazone and was decreased by 25% (P = .068) by pioglitazone. HDL from controls counteracted the inhibitory effect of ox-LDL on vasodilatation (maximal relaxation [Emax] = 74.4% +/- 3.5% vs 51.9% +/- 3.3%, P = .0029), whereas HDL from type 2 diabetic patients did not (Emax = 51.7% +/- 5.8% vs 52.3% +/- 4.6% [P = .66] and 52.7% +/- 5.5% vs 51.9% +/- 4.5% [P = .78] for the rosiglitazone and pioglitazone group, respectively). Rosiglitazone or pioglitazone did not improve Emax (58.6% +/- 5.9% vs 52.3% +/- 4.6% [P = .15] and 49.3% +/- 6.5% vs 51.9% +/- 4.5% [P = .48], respectively). CONCLUSION: Glitazones increased the concentration of HDL cholesterol without restoring the ability of HDL particles to protect the endothelium from oxidative stress-induced dysfunction, meaning that HDL remained dysfunctional with impaired antiatherogenic properties.
Référence
J Clin Endocrinol Metab. 2014 Oct;99(10):E2015-9