Long-term effect of pioglitazone vs glimepiride on lipoprotein oxidation in patients with type 2 diabetes: a prospective randomized study

AimsType 2 diabetes (DM2) is associated to oxidative modifications of high-density lipoproteins (HDL), which can interfere with their function. Pioglitazone has proved effective in raising HDL cholesterol (HDL-C) and lowering small dense low-density lipoprotein (LDL), but no clinical studies have examined its effect on lipoprotein oxidation in patients with DM2.MethodsWe assessed the effect of pioglitazone vs glimepiride after 1year on HDL oxidation, expressed as relative abundance of peptides containing Met(112)O in ApoA-I (oxApoA-I) estimated by mass spectrometry (MALDI/TOF/TOF), in 95 patients with DM2. The oxLDL and AGE were quantified by ELISA.ResultsPatients receiving pioglitazone showed a significant increase in the concentration of ApoA-I (=7.214.8mg/dL, p<0.02) and a reduction in oxApoA-I (=-1.02.6%, p<0.02); this reduction was not significantly different from glimepiride. oxLDL showed a slight, but not significant increase in both treatment groups. Regression analysis showed a correlation between oxApoA-I and AGE (r=0.30; p=0.007) in all patients, while both of these parameters were unrelated to changes in HbA1c, HDL-C, duration of illness, or use of statins.ConclusionsLong-term treatment with pioglitazone was effective in reducing the oxidation of HDL, but not LDL in patients with DM2, while glimepiride didn't. This finding seems to be associated to the change of glyco-oxidation status, not to any improvement in glycemic control or lipid profile.