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

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Abstract

Aims

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.

Methods

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.

Results

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.

Conclusions

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, ClinicalTrials.gov Registered June 18, 2008

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Funding

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.

Author information

Authors and Affiliations

  1. Diabetology and Dietetics, Department of Medicine (DIMED), University of Padova, via Giustiniani, 2, 35100, Padua, Italy

    Giovanni Sartore, Nino Cristiano Chilelli, Silvia Burlina & Annunziata Lapolla

  2. National Research Council-Institute for Energy and Interphases, Padua, Italy

    Roberta Seraglia

  3. Department of Pharmaceutical and Pharmacological Sciences, University of Padova, Padua, Italy

    Eugenio Ragazzi

  4. Lipid Laboratory, Department of Medicine (DIMED), University of Padova, Padua, Italy

    Raffaella Marin

  5. National Research Council-Institute for Energy and Interphases, Padua, Italy

    Marco Roverso

  6. Department of Laboratory Medicine, University of Padova, Padua, Italy

    Chiara Cosma

  7. Department of Clinical Medicine and Surgery, Federico II University, Naples, Italy

    Olga Vaccaro

Authors
  1. Giovanni Sartore
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  2. Nino Cristiano Chilelli
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  3. Roberta Seraglia
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  4. Eugenio Ragazzi
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  5. Raffaella Marin
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  6. Marco Roverso
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  7. Chiara Cosma
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  8. Olga Vaccaro
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  9. Silvia Burlina
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  10. Annunziata Lapolla
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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.

Corresponding author

Correspondence to Nino Cristiano Chilelli.

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

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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.

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

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Sartore, G., Chilelli, N.C., Seraglia, R. et al. Long-term effect of pioglitazone vs glimepiride on lipoprotein oxidation in patients with type 2 diabetes: a prospective randomized study. Acta Diabetol 56, 505–513 (2019). https://doi.org/10.1007/s00592-018-01278-2

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  • DOI: https://doi.org/10.1007/s00592-018-01278-2

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