Diabetology and Dietetics, Department of Medicine (DIMED), University of Padova, via Giustiniani, 2, 35100, Padua, Italy.
National Research Council-Institute for Energy and Interphases, Padua, Italy.
Acta Diabetol. 2019 May;56(5):505-513. doi: 10.1007/s00592-018-01278-2. Epub 2019 Feb 10.
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 MetO 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.
NCT00700856, ClinicalTrials.gov Registered June 18, 2008.
2 型糖尿病（DM2）与高密度脂蛋白（HDL）的氧化修饰有关，这会干扰其功能。吡格列酮已被证明可有效提高 HDL 胆固醇（HDL-C）并降低小而密的低密度脂蛋白（LDL），但尚无临床研究检查其对 DM2 患者脂蛋白氧化的影响。
我们评估了吡格列酮与格列美脲在 1 年后对 95 例 DM2 患者的载脂蛋白 A-I（ApoA-I）氧化的影响，通过质谱（MALDI/TOF/TOF）估计的含甲硫氨酸氧化肽的相对丰度（oxApoA-I）来表示。通过 ELISA 定量 oxLDL 和 AGE。
接受吡格列酮治疗的患者 ApoA-I 浓度显著升高（Δ=7.2±14.8 mg/dL，p<0.02），oxApoA-I 降低（Δ=-1.0±2.6%，p<0.02）；与格列美脲相比，这种降低无显著差异。两组 oxLDL 均略有升高，但无显著差异。回归分析显示，所有患者中 ΔoxApoA-I 与 ΔAGE 之间存在相关性（r=0.30；p=0.007），而这两个参数与 HbA1c、HDL-C、疾病持续时间或他汀类药物的使用无关。
长期使用吡格列酮可有效降低 DM2 患者的 HDL 氧化，但不能降低 LDL 氧化，而格列美脲则没有。这一发现似乎与糖基化氧化状态的变化有关，而与血糖控制或血脂谱的任何改善无关。
NCT00700856，ClinicalTrials.gov 注册，2008 年 6 月 18 日。
