Acta Diabetologica

, Volume 56, Issue 5, pp 505–513 | Cite as

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

  • Giovanni Sartore
  • Nino Cristiano ChilelliEmail author
  • Roberta Seraglia
  • Eugenio Ragazzi
  • Raffaella Marin
  • Marco Roverso
  • Chiara Cosma
  • Olga Vaccaro
  • Silvia Burlina
  • Annunziata Lapolla
Original Article



Type 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.


We assessed the effect of pioglitazone vs glimepiride after 1 year on HDL oxidation, expressed as relative abundance of peptides containing Met112O 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.


Patients receiving pioglitazone showed a significant increase in the concentration of ApoA-I (Δ = 7.2 ± 14.8 mg/dL, p < 0.02) and a reduction in oxApoA-I (Δ = − 1.0 ± 2.6%, 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 ΔoxApoA-I and ΔAGE (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.


Long-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.

Trial registration

NCT00700856, Registered June 18, 2008


Clinical trials Diabetes Mass spectrometry Oxidized lipids Lipoproteins 


Author contributions

NCC wrote the manuscript. GS contributed to study design. NCC, SB, GS researched and analyzed data. AL edited and reviewed manuscript. OV contributed to the discussion. ER contributed to data access and statistical support. RS, RM, MR, CC contributed to data collection and performed the relevant laboratory measurements. All authors read and approved the final version to be published.


This research was supported by the Italian Medicines Agency (AIFA) as part of the Independent Drug Research Program (contract N°. FARM6T9CET), and by Diabete Ricerca, the not-for-profit Research Foundation of the Italian Diabetes Society.

Compliance with ethical standards

Conflict of interest

The authors declared they do not have anything to disclose regarding conflict of interest with respect to this manuscript.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Informed consent

Informed consent was obtained from all individual participants included in the study.

Supplementary material

592_2018_1278_MOESM1_ESM.doc (48 kb)
Supplementary material 1 (DOC 48 KB)


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Copyright information

© Springer-Verlag Italia S.r.l., part of Springer Nature 2019

Authors and Affiliations

  • Giovanni Sartore
    • 1
  • Nino Cristiano Chilelli
    • 1
    Email author
  • Roberta Seraglia
    • 2
  • Eugenio Ragazzi
    • 3
  • Raffaella Marin
    • 4
  • Marco Roverso
    • 5
  • Chiara Cosma
    • 6
  • Olga Vaccaro
    • 7
  • Silvia Burlina
    • 1
  • Annunziata Lapolla
    • 1
  1. 1.Diabetology and Dietetics, Department of Medicine (DIMED)University of PadovaPaduaItaly
  2. 2.National Research Council-Institute for Energy and InterphasesPaduaItaly
  3. 3.Department of Pharmaceutical and Pharmacological SciencesUniversity of PadovaPaduaItaly
  4. 4.Lipid Laboratory, Department of Medicine (DIMED)University of PadovaPaduaItaly
  5. 5.National Research Council-Institute for Energy and InterphasesPaduaItaly
  6. 6.Department of Laboratory MedicineUniversity of PadovaPaduaItaly
  7. 7.Department of Clinical Medicine and SurgeryFederico II UniversityNaplesItaly

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