Department of Medical, Surgical, Neurological, Metabolic and Geriatric Sciences, Second University of Naples, Piazza Miraglia 2, 80138 Naples, Italy.
Atherosclerosis. 2013 Apr;227(2):349-54. doi: 10.1016/j.atherosclerosis.2012.12.018. Epub 2013 Jan 17.
Blood glucose fluctuations have been found to be relevant to the progression of atherosclerosis in patients with type 2 diabetes and to be more detrimental for the development of atherosclerosis than the sustained hyperglycemia. We aim at evaluating the effect of blunted daily acute glucose fluctuations by DPP-IV inhibitors on intima-media thickness (IMT), a surrogate marker for early atherosclerosis.
Data from a 12-week prospective, randomized, open-label parallel group trial with a blinded-endopoint study on 90 patients with DMT2, assessing the role of Dipeptidyl Peptidase-4 inhibition in lowering oxidative stress and inflammation by reducing daily acute glucose fluctuations (MAGE), were included in the present analysis.
Administration of both sitagliptin and vildagliptin treatment resulted in a significant decline in IMT. Indeed, vs baseline data Vildagliptin vs Sitagliptin resulted in a greater IMT reduction. After 3 months therapy changes in IMT significantly correlated with changes in MAGE but not with change in HbA1c in the whole population. Only change in MAGE and LDL plasma levels resulted to be independent predictors of the reduced carotid intima-media thickness after adjusting for conventional cardiovascular risk factors in patients with type 2 diabetes. Significant correlations between change in MAGE, change in IMT and change in fasting and interprandial inflammation score and nitrotyrosine plasma levels were found.
Reduction of glucose excursion due to DPP-IV inhibitors administration, may prevent atherosclerosis progression in patients with type 2 diabetes probably through the reduction of daily inflammation and oxidative stress.
研究发现，血糖波动与 2 型糖尿病患者动脉粥样硬化的进展有关，其对动脉粥样硬化发展的危害甚于持续高血糖。本研究旨在评估二肽基肽酶-4（DPP-4）抑制剂对血糖波动的影响，以评估其对内膜中层厚度（IMT）的影响，后者是动脉粥样硬化早期的替代标志物。
本研究为前瞻性、随机、开放标签的平行分组试验，共纳入 90 例接受 DMT2 治疗的患者，进行为期 12 周的研究，评估二肽基肽酶-4 抑制剂通过降低血糖波动（MAGE）降低氧化应激和炎症的作用。本分析纳入了该试验的终点研究数据。
西格列汀和维格列汀治疗均可显著降低 IMT。与基线数据相比，维格列汀治疗可显著降低 IMT，且降低幅度大于西格列汀。治疗 3 个月后，全人群的 IMT 变化与 MAGE 变化显著相关，但与 HbA1c 变化无关。在校正 2 型糖尿病患者的常规心血管危险因素后，仅 MAGE 和 LDL 血浆水平的变化可独立预测颈动脉内膜中层厚度的降低。在 MAGE、IMT 变化与空腹和餐后炎症评分和硝基酪氨酸血浆水平变化之间发现了显著的相关性。
DPP-4 抑制剂治疗可降低血糖波动，可能通过降低每日炎症和氧化应激来预防 2 型糖尿病患者的动脉粥样硬化进展。
