缺血性中風導致高血糖發生不良預後相關生物標記之研究

TMUIR > College of Public Health > School of Public Health > Dissertations/Theses > Item 987654321/62921

jsp.display-item.identifier=請使用永久網址來引用或連結此文件: http://libir.tmu.edu.tw/handle/987654321/62921

题名:	缺血性中風導致高血糖發生不良預後相關生物標記之研究 Research on Biomarkers of Adverse Prognosis in Post-Stroke Hyperglycemia Patients
作者:	林翰君 LIN, HAN-CHUN
贡献者:	公共衛生學系碩士班邱弘毅
关键词:	缺血性中風;高血糖;生物標記;嗜中性細胞外誘捕網;基因差異化分析 Ischemic Stroke;Hyperglycemia;Biomarker;Neutrophil Extracellular Traps
日期:	2023-06-01
上传时间:	2023-09-22 15:40:29 (UTC+8)
摘要:	腦血管疾病在過去十年，續居於國人十大死因前四名，其中又以缺血性中風為主。過去已知糖尿病是中風的危險因素之一，糖尿病患者較容易發生中風並且增加中風後死亡、殘疾和再復發等不良預後情形。近期研究和臨床發現，不論過去是否有糖尿病，約有50%中風患者於急性期發生高血糖狀態，並且和發生不良預後相關。目前針對高血糖症狀，給予胰島素注射和降血糖藥物治療，但是對於中風患者預後無顯著改善，顯示機制尚不明確。故本篇研究欲探討治療之外，缺血性中風導致高血糖發生不良預後的相關生物標記。本篇研究為兩階段式病例對照研究，所有研究對象皆來自台灣中風遺傳研究資料登錄系統（Formosa Stroke Genetic Consortium, FSGC）。第一階段，共納入8526位缺血性中風患者，區分有無糖尿病和高血糖對中風後不良預後程度差異，並探討其相關危險因子。因此研究對象將分為血糖正常無糖尿病、血糖正常有糖尿病、高血糖有糖尿病、高血糖無糖尿病四組進行探討。另外，使用17位缺血性中風患者RNA定序資料進行基因差異化分析（DEG），尋找缺血性中風後高血糖發生不良預後之候選生物標記。第二階段，共納入1052位缺血性中風患者，使用酵素結合免疫吸附分析法(Enzyme-linked immunosorbent assay, ELISA)驗證該生物標記於中風患者的血漿濃度與不良預後之間關係。結果顯示，無糖尿病之缺血性中風患者於急性期發生高血糖預後不良比例較高，發生死亡風險最高（OR 2.4；95%CI 1.59-3.73）。與高血糖有糖尿病者相比，其發生不良預後因素包含：年齡較長、入院NIHSS（National Institute of Health Stroke Scale, NIHSS）分數較高、罹患心房顫動比例高、心因性栓塞中風比例高。基因差異化分析（DEG）結果顯示，嗜中性細胞外誘捕網（Neutrophil Extracellular Traps, NET）可能是缺血性中風導致高血糖發生不良預後相關生物標記。ELISA實驗結果分析顯示，高血糖無糖尿病之中風患者NET濃度較高；中風後1、3個月預後不良者NET濃度較高。校正影響中風預後相關危險因子，NET濃度增加，發生中風後1個月不良預後風險增加1.3倍（95%CI 1.02-1.73）。分層分析發現，高血糖有糖尿病之中風患者，NET濃度上升，中風後1、3個月不良預後風險顯著增加；高血糖無糖尿病之中風患者，NET濃度上升，中風後1個月不良預後危險性增加。綜合以上所述，本研究結果顯示，高血糖無糖尿病之缺血性中風患者發生不良預後風險較高，並且與患者血漿當中NET濃度上升有關。因此，NET可能可以作為缺血性中風高血糖發生不良預後之生物標記。未來需要進一步探討NET相關機制與缺血性中風患者高血糖之間關聯，有助於改善中風後高血糖相關治療。降低血液中NET濃度，預防中風後不良預後情形發生。 Cerebrovascular diseases continue to rank among the top four causes of death in Taiwan over the past decade, with ischemic stroke being the most common cause. Diabetes is a known risk factor for stroke. People with diabetes are at higher risk of stroke compared to people without diabetes, and they may also have an enhanced prognosis for death, disability, and recurrence after a stroke. Recently, research and clinical findings have shown that hyperglycemia occur in approximately 50% of acute stroke patients no matter who is affected with diabetes or not and is associated with an adverse prognosis. The current treatment of hyperglycemia with insulin and hypoglycemic drugs has not significantly improved the prognosis of patients, indicating that mechanism of stroke induced hyperglycemia is unclear. Therefore, the purpose of this study was to investigate novel biomarkers involved in the mechanism of adverse prognosis in post-stroke hyperglycemia patients. The study was divided into a two-stage case-control study. All study subjects were recruited from the Formosa Stroke Genetic Consortium (FSGC) database, and all of them were ischemic stroke patients. In the first stage, a total of 8526 patients were included. We distinguished the difference in the degree of adverse prognosis of ischemic stroke patients with or without hyperglycemia or diabetes and explored the associated risk factors. Therefore, study subjects are classified into four groups:without hyperglycemia and diabetes (non-HG/non-DM), without hyperglycemia with diabetes (non-HG/DM), with hyperglycemia and diabetes (HG/DM), and with hyperglycemia without diabetes (HG/non-DM). Furthermore, differential expression gene analysis (DEG) was performed using RNA-sequencing data from 17 ischemic stroke patients to identify the candidate biomarkers for adverse prognosis in post-stroke hyperglycemia. A total of 1052 ischemic stroke patients in the second phase will verify the relationship between the biomarker's plasma concentration and poor prognosis in stroke patients was verified using an enzyme-linked immunosorbent assay (ELISA). Our result revealed that the HG/non-DM group had a higher proportion of poor outcome and the highest risk of death(OR 2.43；95%CI 1.59-3.73). Compared with the HG/DM group, the HG/non-DM group had a poor prognosis due to older age, higher NIHSS scores at admission, higher incidence of atrial fibrillation and higher proportion of cardioembolic stroke. DEG shows that neutrophil extracellular traps(NET)may be a relevant biomarker of adverse prognosis in post-stroke hyperglycemia patients. Analysis of the ELISA results showed that NET levels were higher in patients in the HG/non-DM group or those with a poor prognosis at 1and 3 months after stroke. After adjustment for risk factors associated with stroke prognosis, an elevated NET is associated with a 1.3-fold increase in the risk of adverse outcomes one month after stroke. The stratified analysis found that patients in the HG/DM group had elevated NET and a significantly increased risk of poor outcome at 1 and 3 months after stroke, whereas patients in the HG/non-DM group had increased NET levels and a significantly increased risk of adverse prognosis at 1 month after stroke. In summary, patients who had no diabetes and developed hyperglycemia during acute ischemic stroke have a higher risk of adverse prognosis and are associated with increased plasma levels of NET. Therefore, NET may be a biomarker for adverse prognosis in patients with ischemic stroke who have hyperglycemia. In the future, the relationship between NET-related mechanisms and hyperglycemia in ischemic stroke patients needs to be further investigated to improve the treatment of hyperglycemia after stroke. Reducing NET levels in the blood to prevent adverse prognosis after stroke.
描述:	碩士指導教授:邱弘毅委員:邱弘毅委員:李俊泰委員:謝宜蓁
数据类型:	thesis
显示于类别:	[School of Public Health] Dissertations/Theses

文件中的档案:

档案	描述	大小	格式	浏览次数
index.html		0Kb	HTML	90	检视/开启

在TMUIR中所有的数据项都受到原著作权保护.

TAIR相关文章

数据加载中.....