臺灣博碩士論文加值系統

隨著生活型態的改變，各種慢性病的盛行率也逐年增加。糖尿病就是其中之一，佔十大死因的大部份。糖尿病罹患率及死亡率逐漸上升，也有年輕化趨勢。清楚了解糖尿病病理的相關機制是有效預防及控制糖尿病併發症的方式。目前，糖化蛋白終產物（Advanced Glycosylation End Products, AGEs）是臨床上認為與糖尿病併發症產生的主要因素之一。血液糖化血色素(HbA1c)是AGEs的糖化反應產物之一，藉此可了解患者一段時間的血糖濃度，也會影響患者紅血球的脆性。同樣，血清中AGEs濃度是否也同樣會使紅血球脆性改變！因此，本研究探討第2型糖尿病血液AGEs濃度與血球脆性的相關性。研究受試者為新竹某家醫院隨機取得90名有效樣本（男性47人，女性43人，平均年齡為60.63±10.68歲及57.60±14.73歲），方法是採取常規血液分析（CBC）、HbA1c分析、紅血球滲透脆性試驗、血糖、AGEs之酵素免疫分析（Enzyme-linked immunosorbent assay;ELISA）。首先將樣本之HbA1c濃度區分為小於或等於6%及大於6%兩組，然後進行測血糖、CBC、AGEs-ELISA、紅血球滲透脆性試驗分析。結果顯示兩組樣本在紅血球脆性實驗之開始溶血（P=0.134）和完全溶血（P=0.475）在性別差異上並無明顯差別；兩組樣本之AGEs濃度在性別上也無顯著差異性（P=0.058）。糖化血色素小於6％大於6％開始溶血（P=0.474）和完全溶血（P=0.456）在糖化血色素並無明顯差異；AGEs濃度在糖化血色素上也無顯著差異性（P=0.097）。年齡小於65歲大於65歲開始溶血(P=0.290)和完全溶血(P=0.081)在年齡上並無明顯差別；AGEs濃度在年齡上也無顯著差異性（P=0.124）。開始溶血與AGEs（P=0.764）；完全溶血與AGEs（P=0.564）無密切相關性。這項研究結論，AGEs濃度雖然在糖尿病患者及非糖尿病樣本中有明顯差別（p<0.001），但與HbA1C濃度的呈現沒有統計學上的關聯（p=0.097），且也與與紅血球脆性之間並無差異。

Following the changes in lifestyles, the prevalence of various chronic diseases is on the increase year by year. Among these chronic diseases, diabetes accounts for the majority of the top 10 causes of death. In addition to the gradually rising morbidity and mortality in diabetes, there are more and more young patients suffering from it. To effectively prevent and control diabetic complications, it is important to clarify the pathological nature of diabetes.
At present, the advanced glycosylation end products (AGEs) are clinically considered as one of the main factors associated with diabetes complications. The blood glycosylated hemoglobin (HbA1c), as one of the glycosylation products of AGEs, may be used to assess a blood glucose level over a period of time. Moreover, HbA1c plays a role in the changes in fragility of red blood cells. It would be interesting to know whether the serum AGEs level could be similarly involved in changes in red blood cell fragility. Therefore, this study seeks to investigate the correlation between blood AGEs concentrations and red blood cell fragility in type 2 diabetes mellitus.
The study subjects were 90 valid randomized samples (47 males with a mean age of 60.63±10.68 years; 43 females with a mean age of 57.60±14.73 years) enrolled from a hospital in Hsinchu for complete blood count (CBC), HbA1c assays, red blood cell osmotic fragility tests, blood glucose tests and enzyme-linked immunosorbent assays (ELISAs) of AGEs. First, the samples were divided into two groups: one group with HbA1c concentrations no greater than 6% and the other group with concentrations greater than 6%. Subsequently, they were analyzed using blood glucose tests, CBCs, AGEs-ELISAs, red blood cell osmotic fragility tests.
In the results, it has been shown that between genders, both groups had no significant difference of beginning hemolysis (P=0.134) and complete hemolysis (P=0.475) in red blood cell fragility tests. There was no significant difference (P=0.058) of AGEs concentrations between genders either. For glycosylated hemoglobin, there was no significant difference of the beginning hemolysis (P=0.474) and complete hemolysis (P=0.456) between the groups with glycosylated hemoglobin less and greater than 6%. The AGEs concentrations were not significantly different (P=0.097) between the different glycosylated hemoglobin levels either. As to their ages, there was no significant difference of beginning hemolysis (P=0.290) and complete hemolysis (P=0.081) between the ages of less and more than 65 years. The AGEs concentrations were not significantly different (P=0.124) between ages. In addition, the beginning hemolysis was not closely correlated with the AGEs levels (P=0.764). The complete hemolysis was not closely correlated with AGEs levels (P=0.564) either.
In conclusion for this study, although AGEs concentrations are significantly different between patients with diabetes and the control samples (p<0.001), it has been shown that those are not statistically correlated with the HbA1C concentrations (p=0.097) and there is no difference in red blood cell fragility between those.

目錄
致謝.............................................................................................................I
中文摘要....................................................................................................III
英文摘要....................................................................................................IV
目錄............................................................................................................VI
表目錄........................................................................................................XI
圖目錄........................................................................................................XII
第一章 緒論.
1.1研究背景和動機............................................................................1
1.2研究目的........................................................................................4
第三章 文獻探討
2.1糖尿病的流行病學........................................................................5
2.2.1糖尿病併發症…...................................................................6
2.3細胞的液體環境............................................................................8
2.4紅血球NaCl-PO4溶液環境反應..................................................8
2.5高血糖脆性反應............................................................................9
2.6糖尿病與自由基及氧化壓力........................................................9
2.7高血糖活化糖化蛋白終產物.......................................................10
2.8高血糖活化糖化蛋白終產物與高血糖活化糖化蛋白終產物受
體...................................................................................................10
2.9糖化蛋白終產物與發炎反應.......................................................11
2.10糖化蛋白終產物對組織細胞傷害.............................................11
第三章 材料與方法
3.1實驗材料.......................................................................................13
3.1.1檢體收集及儲存方法..........................................................13
3.1.2試劑與材料..........................................................................13
3.1.3 NaCl-PO4溶液濃度配製及儲存........................................14
3.1.4糖化蛋白終產物稀釋清洗緩衝配置..................................14
3.1.5糖化蛋白終產物試劑配置..................................................15
3.1.6糖化蛋白終產物抗體及稀釋配置......................................15
3.2儀器設備.......................................................................................15
3.3研究方法與步驟...........................................................................16
3.3.1血糖分析原理......................................................................16
3.3.2全血細胞技數分析原理......................................................16
3.3.2.1紅血球數量.............................................................16
3.3.2.2血紅素.....................................................................17
3.3.2.3血球容積比.............................................................17
3.3.2.4平均紅血球容積.....................................................18
3.3.2.5平均紅血球血紅素.................................................18
3.3.2.6平均紅血球血紅素濃度.........................................19
3.3.2.7紅血球分佈密度......................................................19
3.3.2糖化血色素儀器分析原理...................................................19
3.3.3蛋白質定量原理...................................................................20
3.3.4紅血球脆性試驗原理...........................................................20
3.3.4.1分析步驟..................................................................21
3.3.5糖化蛋白終產物酵素免疫分析法.......................................21
3.3.5.1分析步驟..................................................................22
3.4統計分析........................................................................................23
第四章 結果
4.1年齡、性別及各生化檢查值分析結果........................................24
4.2糖尿病和非糖尿病對照生化檢查值分析....................................24
4.3各生化分析與糖化血色素分析....................................................25
4.3各生化檢查結果在第一組樣本（糖化血色素小於6%）之性別
上差異............................................................................................25
4.4各生化檢查結果在第二組（糖化血色素大於6%）之性別上差
異....................................................................................................26
4.5年齡族群及各生化檢查結果........................................................26
4.6糖化蛋白終產物與紅血球脆性之相關性....................................26
第五章 討論
5.1糖尿病及非糖尿病的相關性........................................................28
5.2最終糖化蛋白終產物（AGEs）與糖尿病相關性......................28
5.3血球脆性與糖尿病的相關性.........................................................29
5.4最終糖化蛋白終產物（AGEs）與糖化血色素（HbA1c）的相
關性.................................................................................................29
5.5糖化蛋白終產物（AGEs）與血脆之間相關性...........................30
5.6糖化蛋白終產物（AGEs）與年齡差異的相關性.......................31
5.7糖化蛋白終產物（AGEs）與性別差異的相關性.......................32
5.8紅血球脆性與年齡層差異的相關性..............................................32
5.9血球脆性與性別差異的相關性......................................................33
第六章 參考文獻
一、 英文部分.....................................................................................34
二、 中文部分.....................................................................................40

第六章 文獻

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二、中文部分
1. 行政院衛生署衛生統計重要指標　
http://www.gov.tw/statistic/data 衛生統計重要指標。

2. 行政院衛生署國民健康局中老年保健-台灣糖尿病防治推動現況與展望
http://www.bhp.doh.gov.tw/BHP/index.jsp。

3. 房晶萍，「糖尿病患者和微血管及血管病變指標的臨床觀察」Chin Hemorh，民國93年。

4. 黃展偉，黃國晉，楊偉勛，「美國糖尿病學會臨床治療指引摘要.家庭醫學與基層醫療」，民國99年。

5. 譚健民，「美國糖尿病協會(ADA)糖尿病診療標準指引摘要」，財團法人宏恩綜合醫院內科，民國100年。

6. 黃毅，黃金花，謝青季，姚守拙，「糖與蛋白質相互作用」，化學進展，民國97年。

7. 蔡志忠，陳皓君，「生物體內沒那反應的化學與抑制」國立中正大學化學系暨化學研究所，民國91年。

8. 李姸嬅，「慢性疾病性對醫療資源耗用因素之探討-以糖尿病為例」，國立雲林科技大學工業工程與管理研究所碩士論文，民國102年。

9. 蔡佩璇，「麩醯胺補充對STZ誘導糖尿病鼠發炎反應與氧化壓力之影響」，臺北醫學大學保健營養學系博士論文，民國106年。

10. 付漢菁，潘素芳，朱良湘，袁申元，李延延，許世清，「糖尿病患者紅血球和滲透脆性初步研究」，民國87年。

11. 葉振山，「階層式計算方法診斷小血球性貧血」國立雲林科技大學資訊管理系碩士論文，民國93年。

12. 林宏達，「認識糖尿病」，民國92年。

13. 徐颷，王建民，「胃癌流行病學研究」，民國95年。

14. 韓春茂，岳曉， Stig Bengmark，「最終糖化蛋白終產物與食物」，中華臨床營養，民國98年。

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16. 龔妙妃，「血液透析病患常見貧血原因之治療及護理」，民國91年。

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