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2型糖尿病并发症发生过程中,天冬氨酸、簇集蛋白、锌α-2-糖蛋白、核因子κB及过氧化物酶体增殖物激活受体γ之间的关联

The Associations between Asprosine, Clusterin, Zinc Alpha-2-Glycoprotein, Nuclear Factor Kappa B, and Peroxisome Proliferator-Activated Receptor Gamma in the Development of Complications in Type 2 Diabetes Mellitus.

作者信息

Senyigit Abdulhalim, Durmus Sinem, Tabak Omur, Oruc Aykut, Uzun Hafize, Ekinci Iskender

机构信息

Department of Internal Medicine, Faculty of Medicine, Istanbul Atlas University, 34403 Istanbul, Turkey.

Department of Medical Biochemistry, Faculty of Medicine, Katip Celebi University, 35620 Izmir, Turkey.

出版信息

J Clin Med. 2024 Oct 14;13(20):6126. doi: 10.3390/jcm13206126.

Abstract

: The aim of this study was to investigate the circulating levels of asprosin, clusterin, zinc-alpha-2-glycoprotein (ZAG), nuclear factor-kappa B (NF-κB), and peroxisome proliferator-activated receptor-gamma (PPAR-γ) in patients with T2DM in relation to microvascular and macrovascular complications. Measuring these biomarkers may provide insight into the pathophysiology of T2DM and indicate novel targets for the therapy of diabetes-related complications. : A total of 260 subjects consisting of four groups: healthy controls (Group-1), T2DM patients without complications (Group-2), T2DM patients with microvascular complications (Group-3), and T2DM patients with macrovascular complications (Group-4). : The mean age of all subjects was 52.96 ± 6.4, 127 of whom were male. Asprosin, clusterin, and NF-κB levels were significantly higher, while ZAG and PPAR-γ levels were significantly lower in diabetic patients than healthy subjects ( < 0.01, for all). Asprosin ( < 0.01), clusterin ( < 0.01), and NF-κB (: 0.002) levels were significantly higher and PPAR-γ ( < 0.01) level was significantly lower ( < 0.001) in Group-3 than Group-2. Asprosin ( < 0.01) and NF-κB (: 0.011) levels were significantly higher while ZAG ( < 0.01) level was significantly lower in Group-4 than Group-2. Serum ZAG level was found lower in Group-4 than in Group-3 ( = 0.037). Further, the biomarkers presented significant correlation with biomarkers like HbA1c and HOMA-IR. It was observed that increasing serum asprosin, clusterin, and NF-κB levels and decreasing serum PPAR-γ levels were effective in the development of microvascular complications while the increased asprosin levels and decreased ZAG levels had a significant effect on the development of macrovascular complications in the binary logistic regression analysis. : This study confirms that altered levels of asprosin, clusterin, ZAG, NF-κB, and PPAR-γ are associated with T2DM and its complications. These biomarkers reflect the pathophysiological processes of metabolic disturbance and inflammation in T2DM and, therefore, have the potential for use in targeted interventions to prevent and manage diabetes-related complications.

摘要

本研究旨在调查2型糖尿病(T2DM)患者中阿朴脂蛋白、簇集蛋白、锌α2糖蛋白(ZAG)、核因子κB(NF-κB)和过氧化物酶体增殖物激活受体γ(PPAR-γ)的循环水平与微血管和大血管并发症的关系。检测这些生物标志物可能有助于深入了解T2DM的病理生理学,并为糖尿病相关并发症的治疗指明新的靶点。

共有260名受试者,分为四组:健康对照组(第1组)、无并发症的T2DM患者(第2组)、有微血管并发症的T2DM患者(第3组)和有大血管并发症的T2DM患者(第4组)。

所有受试者的平均年龄为52.96±6.4岁,其中127人为男性。糖尿病患者的阿朴脂蛋白、簇集蛋白和NF-κB水平显著升高,而ZAG和PPAR-γ水平显著低于健康受试者(所有P均<0.01)。第3组的阿朴脂蛋白(P<0.01)、簇集蛋白(P<0.01)和NF-κB(P=0.002)水平显著高于第2组,而PPAR-γ(P<0.01)水平显著低于第2组(P<0.001)。第4组的阿朴脂蛋白(P<0.01)和NF-κB(P=0.011)水平显著高于第2组,而ZAG(P<0.01)水平显著低于第2组。发现第4组的血清ZAG水平低于第3组(P=0.037)。此外,这些生物标志物与糖化血红蛋白(HbA1c)和稳态模型评估胰岛素抵抗(HOMA-IR)等生物标志物呈现显著相关性。在二元逻辑回归分析中观察到,血清阿朴脂蛋白、簇集蛋白和NF-κB水平升高以及血清PPAR-γ水平降低对微血管并发症的发生有影响,而阿朴脂蛋白水平升高和ZAG水平降低对大血管并发症的发生有显著影响。

本研究证实,阿朴脂蛋白、簇集蛋白、ZAG、NF-κB和PPAR-γ水平的改变与T2DM及其并发症相关。这些生物标志物反映了T2DM中代谢紊乱和炎症的病理生理过程,因此有可能用于预防和管理糖尿病相关并发症的靶向干预。

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