title: No improvement of high-density lipoprotein (HDL) vasorelaxant effect despite increase in HDL cholesterol concentration in type 2 diabetic patients treated with glitazones.
abstract: BACKGROUND
  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.
  
  
  OBJECTIVE
  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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Inserm U866 (L.P., L.D., S.M., B.B., J.-M.P., B.V.), University of Burgundy, Médecine; Department of Biochemistry (L.D.), Universitary Hospital Plateau Technique de Biologie; and Department of Endocrinology and Metabolic Diseases (M.-C.B., B.B., J.-M.P., B.V.), CHU, Hôpital du Bocage, Dijon F-21000 France.
authors.forename: Laurence
authors.initials: L
authors.lastname: Perségol
authors.forename: Laurence
authors.initials: L
authors.lastname: Duvillard
authors.forename: Serge
authors.initials: S
authors.lastname: Monier
authors.forename: Marie-Claude
authors.initials: MC
authors.lastname: Brindisi
authors.forename: Benjamin
authors.initials: B
authors.lastname: Bouillet
authors.forename: Jean-Michel
authors.initials: JM
authors.lastname: Petit
authors.forename: Bruno
authors.initials: B
authors.lastname: Vergès
mesh_terms: D000368:Aged; D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000502:physiology; D008076:Cholesterol, HDL / Q000097:blood*; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000378:metabolism*; D050171:Dyslipidemias / Q000188:drug therapy / Q000378:metabolism; D004730:Endothelium, Vascular / Q000187:drug effects / Q000502:physiology; D005260:Female; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use; D008075:Lipoproteins, HDL / Q000097:blood*; D008077:Lipoproteins, LDL / Q000097:blood; D008297:Male; D008875:Middle Aged; D000077205:Pioglitazone; D011817:Rabbits; D000077154:Rosiglitazone; D045162:Thiazolidinediones / Q000627:therapeutic use*; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology*
chemical_list: D008076:Cholesterol, HDL; D007004:Hypoglycemic Agents; D008075:Lipoproteins, HDL; D008077:Lipoproteins, LDL; D045162:Thiazolidinediones; C099252:oxidized low density lipoprotein; D000077154:Rosiglitazone; D000077205:Pioglitazone