Department of Pharmaceutical and Pharmacological Sciences, University of Padova, Padova, Italy.
Department of Medicine - DIMED, University of Padova, Padova, Italy.
Front Endocrinol (Lausanne). 2023 Aug 11;14:1163554. doi: 10.3389/fendo.2023.1163554. eCollection 2023.
The ratio between advanced glycation end products (AGEs) and soluble form of receptor (s-RAGE) has been proposed as a risk marker for renal and cardiovascular diseases. The aim of this study was to evaluate in the diabetes condition the influence of two different oral anti-diabetic treatments on the AGE/s-RAGE ratio, during a 5-year observation period.
Seventy-three patients with type 2 diabetes mellitus were randomly assigned to a drug therapy with pioglitazone or glimepiride, combined to metformin. Each subject was evaluated at baseline and after 5 years of treatment.
In both groups s-RAGE levels did not significantly vary, while the levels of AGE and AGE/s-RAGE were both significantly reduced, basal compared to 5-year values. Within pioglitazone group, as well within glimepiride group, significant variations (Δ, as difference between 5 years of treatment minus basal) were observed for AGE (Δ= -21.1±13.4 µg/ml, <0.001 for pioglitazone; Δ= -14.4±11.4 µg/ml, <0.001 for glimepiride) and in AGE/s-RAGE (Δ= -0.037±0.022 µg/pg, <0.001 for pioglitazone; Δ= -0.024±0.020µg/pg, <0.001 for glimepiride), suggesting an average decrease of the parameters by more than 50% in both treatments. Pioglitazone was more effective than glimepiride in reducing AGE/s-RAGE ratio after 5 years of therapy.
These data can help to explain the benefits of oral anti-diabetic therapy in relation to the reduction of cardiovascular risk, as suggested by variations in AGE/s-RAGE ratio as biochemical marker of endothelial function; in particular, treatment with pioglitazone seems to offer greater long-term benefit on AGE-RAGE axis.
糖化终产物（AGE）与可溶性受体（s-RAGE）的比值已被提出作为评估肾脏和心血管疾病风险的标志物。本研究旨在评估在糖尿病患者中，两种不同的口服降糖药物治疗在 5 年观察期内对 AGE/s-RAGE 比值的影响。
73 例 2 型糖尿病患者被随机分配至吡格列酮或格列美脲联合二甲双胍的药物治疗组。所有患者在基线时和治疗 5 年后均进行评估。
两组 s-RAGE 水平均无显著变化，而 AGE 和 AGE/s-RAGE 水平均显著降低，与 5 年时相比。在吡格列酮组和格列美脲组中，AGE（吡格列酮组：Δ=-21.1±13.4 µg/ml，<0.001；格列美脲组：Δ=-14.4±11.4 µg/ml，<0.001）和 AGE/s-RAGE（吡格列酮组：Δ=-0.037±0.022 µg/pg，<0.001；格列美脲组：Δ=-0.024±0.020µg/pg，<0.001）均有显著变化，提示两种治疗方法均可使参数降低超过 50%。吡格列酮在降低 AGE/s-RAGE 比值方面比格列美脲更有效。
这些数据有助于解释口服降糖治疗对降低心血管风险的益处，因为 AGE/s-RAGE 比值的变化作为内皮功能的生化标志物；特别是，吡格列酮治疗在 AGE-RAGE 轴方面似乎提供了更大的长期获益。
