Department of Medical Biochemistry, Wroclaw Medical University, Poland.
Department of Angiology, Diabetes and Hypertension, Wroclaw Medical University, Poland.
Adv Clin Exp Med. 2020 Mar;29(3):275-284. doi: 10.17219/acem/112611.
Advanced glycation end products (AGEs) are formed during protein modification by a reduction of sugars or reactive aldehydes. Depending on the pathology, various AGEs may be formed. They are stable compounds and are considered as potential diseases markers.
The objective of this study was to assess glucose-mediated albumin modification that yields non-standard epitopes of AGEs (AGE-1) in diabetes and in associated metabolic abnormalities.
The AGE-1, expressed as median AGE-1 level and AGE-1 positivity, was determined in 246 individuals (198 with prediabetes/diabetes) using a new slot-dot-blot method (allowing for detection of barely traceable analytes) and related to the presence of diabetes-associated metabolic abnormalities and complications, and treatment.
The AGE-1 level was higher in patients with prediabetes/diabetes than in controls. Its elevation was associated with metabolic syndrome (MetS), obesity, hyperlipidemia, and non-alcoholic fatty liver disease (NAFLD) but not with diabetic control or microand macroangiopathy, except for atherosclerotic plaques formation in carotid arteries. The AGE-1-positive patients had higher triglycerides and lower high-density lipoprotein (HDL)-cholesterol. In patients untreated with aspirin, AGE-1 positivity was associated with higher C-reactive protein (CRP) level. Treatment with aspirin, sulfonylureas and gliptins was associated with higher AGE-1 level and with dyslipidemia medications with higher AGE-1 positivity. In patients with abnormal glucose metabolism, acarbose treatment was associated with lower AGE-1 positivity. Multivariate analysis showed MetS, carotid artery plaques, NAFLD, and treatment with aspirin and acarbose to be independently associated with AGE-1 positivity.
Unlike standard AGEs, AGE-1 is more tightly associated with abnormalities in lipid than glucose metabolism, and lower in patients treated with acarbose but not with other antidiabetics.
在蛋白质被糖或反应性醛还原修饰的过程中会形成晚期糖基化终产物（AGEs）。根据病理学的不同，可能会形成各种 AGEs。它们是稳定的化合物，被认为是潜在的疾病标志物。
本研究旨在评估糖尿病及相关代谢异常中葡萄糖介导的白蛋白修饰产生的非标准 AGEs 表位（AGE-1）。
使用新的插槽斑点印迹法（允许检测几乎难以察觉的分析物）测定 246 个人（198 名有前驱糖尿病/糖尿病）的 AGE-1（表示为中位数 AGE-1 水平和 AGE-1 阳性），并将其与糖尿病相关代谢异常和并发症以及治疗相关联。
前驱糖尿病/糖尿病患者的 AGE-1 水平高于对照组。其升高与代谢综合征（MetS）、肥胖、血脂异常和非酒精性脂肪肝（NAFLD）有关，但与糖尿病控制或微血管和大血管病变无关，除了颈动脉粥样硬化斑块形成。AGE-1 阳性患者的甘油三酯较高，高密度脂蛋白（HDL）-胆固醇较低。未服用阿司匹林的患者中，AGE-1 阳性与 C 反应蛋白（CRP）水平升高有关。服用阿司匹林、磺酰脲类和格列汀类药物与血脂异常药物与较高的 AGE-1 阳性有关。在葡萄糖代谢异常的患者中，阿卡波糖治疗与较低的 AGE-1 阳性有关。多变量分析显示，MetS、颈动脉斑块、NAFLD 以及阿司匹林和阿卡波糖的治疗与 AGE-1 阳性独立相关。
与标准 AGEs 不同，AGE-1 与脂质代谢异常的相关性比葡萄糖代谢异常更紧密，在服用阿卡波糖的患者中较低，但在服用其他抗糖尿病药物的患者中则没有。
