臺灣博碩士論文加值系統

糖尿病在全球過去十年內一直高居主要死因之一，而在國內糖尿病為國人最常見的慢性病之一，近三年的十大死因中更是持續位居第五大死因，嚴重的影響到國人的健康與生活品質。短暫性腦中風發作又稱為小中風，為腦血管疾病的一種，而在中華民國衛生福利部統計資料中顯示，腦血管疾病高居本國十大死因中的第三位，為國人所重視的疾病之一。研究發現斯達汀類(Statins)藥物除了廣泛用於治療高血脂，同時存在抗發炎及改善內皮細胞功能障礙等其他不同機制的多效性(Pleiotropic effect)，且在血管性疾病的預防效能已被證實。然而過去研究顯示，斯達汀類藥物可能增加新發糖尿病的風險，但其作用仍未定論，且藥物機轉仍未明確。因此，本研究欲探討短暫性腦缺血發作族群在使用斯達汀類藥物後發生新診斷糖尿病的風險關係，希望藉此分析斯達汀類藥物對於短暫性腦缺血發作族群發生糖尿病的風險，進一步證實其藥理機轉。
本研究使用全民健康保險研究資料庫2000年百萬承保抽樣歸人檔，分析自1997年1月1日至2011年12月31日間短暫性腦缺血發作新發個案，選取進入研究一年以上的個案，因短暫性腦缺血發作入院者，其中斯達汀類藥物的使用情形由用藥紀錄中獲取，將此藥物依照累積每日定義劑量(Cumulative Defined Daily Doses, cDDDs)進行評估。本研究分析初步使用Cox比例風險模式探討斯達汀類藥物使用對於新診斷糖尿病發生之影響關係；考量個人於時間上的用藥差異，進一步使用時間相依共變數之Cox比例風險模式，並在校正性別、年齡、收入、都市化程度後，計算危險比(hazard ratio, HR) 及其 95%信賴區間。
本研究結果發現，短暫性腦缺血發作患者使用斯達汀類藥物，降低其後發生糖尿病之風險。依照累積每日定義劑量將個案分成低、中、高劑量，其發生糖尿病之風險亦呈現劑量效應關係。作用藥理機轉，未來值得進一步深入探討。

Diabetes Mellitus (DM) is a major public health issue in Taiwan, and worldwide, affecting the health of people and quality of life. Transient Ischemic Attack (TIA) is an important cerebrovascular disease in Taiwan, the third leading mortality cause in Taiwan. Statins are the widely used for hyperlipidemia by their cholesterol-lowering effect, also potentially with pleiotropic effect. Statins potentially can reduce the risk of TIA patients developing more severe stroke. Some studies have shown statins use maybe related to the risk of developing DM but the results remain controversial. Therefore, the aim of this study was to investigate the risk of developing DM after using statins among TIA patients.
The study design was a retrospective cohort study based on Taiwan Longitudinal Heath Insurance Database 2000 (LHID2000). This study subjects were newly diagnosed cases of transient ischemic attack from January 1, 1997 to December 31, 2011. Statin dose is assessed and evaluated according to the cumulative daily defined dose (cDDDs). Cox proportion hazard regression models were used to investigate the relationship between the use of statins and the risk of newly diagnosed DM among TIA patients. Considering the differences within the time period of personal use statins, the Cox proportional hazards model with time-dependent covariate was used to calculate the hazard ratio (HR) and 95% confidence interval (95% CI) after adjusting the sex, age, income and urbanization degree. Sensitivity analysis and subgroup analysis were also conducted. All hypothesis tests for statistical significance were 2-sided using p <0.05.
The results showed that TIA patient statins use may reduce the risk of newly diagnosed DM. According to the cumulative daily dose, three exposure groups being analyzed (low, medium and high doses), dose-response relationship were found. More research is needed for the mechanism and effect of statins among TIA patients related to DM.

誌謝 i
中文摘要 ii
Abstract iv
目錄 vi
表目錄 viii
圖目錄 ix
第一章 緒論 1
第一節 研究背景與研究動機 1
第二節 研究的重要性 2
第三節 研究目的 3
第四節 研究問題與研究假設 3
第五節 名詞界定 4
第二章 文獻查證 6
第一節 腦血管疾病與短暫性腦缺血發作介紹 6
2.1.1短暫性腦缺血發作 7
第二節 糖尿病 9
第三節 斯達汀類(Statins)藥物 11
第四節 使用斯達汀類(Statins)藥物與新發糖尿病的關係 13
第五節 糖尿病之其他相關因素 15
2.5.1人口學及生活習慣因素 15
性別 15
年齡 16
都市化程度 16
社經地位與收入 17
酒精使用 17
吸菸 18
2.5.2疾病共病症及風險因子 18
高血壓 18
高血脂 19
心房顫動 20
慢性腎臟病 20
第六節 糖尿病與腦血管疾病之相關合併藥物 20
第三章 材料與方法 22
第一節 研究設計 22
第二節 研究架構 23
第三節 研究工具 24
3.3.1全民健康保險資料庫 25
第四節 資料收集過程 26
3.4.1研究對象選取 26
3.4.2疾病篩選 27
3.4.3用藥紀錄與計算單位 28
第五節 資料統計與分析 30
3.5.1描述性統計 31
3.5.2分析性統計 31
3.5.3敏感性分析 31
第四章 研究結果 32
第五章 討論 51
第六章 結論與建議 56
第一節 結論 56
第二節 應用與建議 56
參考文獻 57

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