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| 研究生： |
楊珺婷 Yang, Chun-Ting |
|---|---|
| 論文名稱： |
台灣第二型糖尿病病人於胰島素介入治療後之長期糖尿病併發症與安全性之分析 Long-term diabetes-related complications and safety of insulin use among type 2 diabetes patients in Taiwan |
| 指導教授： |
歐凰姿
Ou, Huang-Tz |
| 學位類別： |
碩士 Master |
| 系所名稱： |
醫學院 - 臨床藥學與藥物科技研究所 Institute of Clinical Pharmacy and Pharmaceutical sciences |
| 論文出版年： | 2017 |
| 畢業學年度： | 105 |
| 語文別： | 中文 |
| 論文頁數： | 144 |
| 中文關鍵詞： | 胰島素 、大小血管病變 、死亡 、低血糖 、長效型胰島素 |
| 外文關鍵詞： | insulin, vascular outcomes, death, hypoglycemia, long-acting insulin |
| 相關次數： | 點閱：91 下載：7 |
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研究背景
根據2017年美國糖尿病協會所發布之治療指引，若第二型糖尿病病人已使用三種以上非胰島素類降血糖藥品卻仍無法控制血糖時，應開始介入胰島素治療。近年來，陸續有大型前瞻性研究發表，針對無法以口服降血糖藥品有效控制血糖者，胰島素治療可以顯著改善短期血糖控制，但是在長期療效與安全性的部分仍存有許多爭議。此外，對於已使用三種口服降血糖藥品卻仍無法穩定控制血糖者而言，雖然治療指引建議下一步應開始胰島素治療，但目前相關研究所能提供之臨床證據仍非常缺乏。因此，本研究將針對此族群進行探討，當病人已使用三種口服降血糖藥品卻仍無法穩定控制第二型糖尿病時，下一步應考慮加上胰島素或是繼續加強口服降血糖藥品的治療呢？哪一種治療策略較能夠對長期之大小血管病變以及低血糖帶來較低的風險呢？
研究目的
針對已使用三種口服降血糖藥品仍無法穩定控制血糖之第二型糖尿病病人而言，下一步治療加上胰島素作為第四線治療藥品，比起將目前三種口服降血糖藥品都加至最大劑量或是加上第四線口服降血糖藥品，是否能夠降低長期糖尿病相關血管病變與死亡風險，並評估胰島素治療所帶來之低血糖風險。
研究方法
本研究採回溯性世代研究。研究族群為1999-2010年間穩定使用三種口服降血糖藥品之第二型糖尿病病人，且在2004-2010年間初次使用胰島素 (第四線胰島素使用者) 或是初次於同一筆處方中被開立三種最大劑量之口服降血糖藥品或四種口服降血糖藥品者 (應使用胰島素而未使用者)。主分析中，本研究排除在新使用研究藥品的前一年內有大小血管病變病史之族群，追蹤至資料終止或是病人於資料庫中最後一筆記錄。利用propensity score matching校正研究族群之基本特徵差異，以Cox proportional hazard model比較兩組別之大小血管病變、低血糖、死亡風險。並依照第四線胰島素使用者所接受之胰島素治療方案進行次族群分析，以及調整各操作型定義以進行敏感性分析。
研究結果
對於已使用三種口服降血糖藥品卻仍無法穩定控制血糖之第二型糖尿病病人，第四線胰島素使用者比起應使用胰島素而未使用者之各研究觀察結果 (HR, 95% CI) 如下，心血管事件總和 (1.37, 0.99-1.89)、心肌梗塞與腦血管事件總和 (1.22, 0.81-1.86)、小血管事件總和 (1.03, 0.90-1.17)、周邊血管疾病 (1.20, 0.91-1.58)、低血糖 (1.45, 1.02-2.07)、死亡 (1.53, 0.80-2.94)。第四線胰島素使用者有較高但未達統計上顯著差異的血管病變與死亡風險，以及顯著較高之低血糖風險。若將低血糖放入Cox model中作為校正因子時，部分血管病變之風險比點估計值有下降的趨勢，而在次族群分析以及敏感性分析中也有觀察到相似的現象。本研究推估，胰島素治療所帶來之低血糖風險，可能是造成第四線胰島素使用者有較高血管病變與死亡風險的原因之一。而若針對長效型胰島素使用者進行次族群分析，與應使用胰島素而未使用胰島素者相較之下，在大多血管病變上，有較低的初估發生率及風險比點估計值，雖皆未達統計上顯著差異，但推測可能是因為人數較少與事件數不足導致。長效型胰島素對於長期血管病變，可能是有保護效果的，但未來仍需要更多相關研究支持此論點。
研究結論
針對無法以三種口服降血糖藥品控制血糖之第二型糖尿病病人，加上第四線胰島素比起加上第四線口服降血糖藥品，或將三種口服降血糖藥品加至最大劑量，在長期血管病變及死亡風險上並無顯著差異，但是第四線胰島素使用者有顯著較高之低血糖風險。本研究推測低血糖可能會加重第四線胰島素使用者之長期血管病變及死亡風險。此外，本研究也發現長效型胰島素對於長期血管病變與死亡可能有保護效果。未來，若第二型糖尿病病人無法以三種口服降血糖藥品穩定控制血糖，而需加上胰島素作為下一步治療時，醫療人員與病人皆應嚴密注意低血糖風險，避免低血糖事件的發生。而日後若有更多實證支持，且病人臨床照護狀況許可，應考慮使用長效型胰島素作為胰島素之起始治療。
Insulin is recommended as intensification therapy in the type 2 diabetes (T2DM) patients who fail to achieve glycemic control under triple therapy. However, there is insufficient evidence about long-term vascular effects of insulin therapy in this population. This study aimed to estimate the risks of vascular outcomes, hypoglycemia, and all-cause death of 4th line insulin users compared to those with indication for insulin therapy but using oral anti-diabetic drugs (OADs). Selection criteria of study population include newly diagnosed T2DM during 1999-2010, newly prescribed with insulin (4th line insulin users) or with 3 maximal doses of OADs or 4 OADs (potential insulin candidates, PICs) during 2004-2010, and stable triple OADs use at 1 year before index date. Index date was defined as the first date of insulin use in the 4th line insulin users and the first date of 3 maximal doses of OADs or 4 OADs prescribed in the PICs. In primary analysis, those with diabetes-related complications were excluded and the patients were followed until the last record in the database or the end of the database. Propensity score matching (PSM) was used to control for the baseline imbalances and Cox proportional hazard model was used to evaluate the risk of study outcomes. Study results revealed that 4th line insulin users were associated with non-significantly higher risk of vascular outcomes, all-cause death and significantly higher risk of hypoglycemia compared to PICs. However, the point estimates of hazard ratios were reduced after adjusted by hypoglycemia. We assumed that the higher risks of vascular outcomes and all-cause death observed in this study would be partly explained by hypoglycemia. Additionally, we found that long-acting (LA) insulin may have protective effects on vascular outcomes. The prospective trials that corroborate the results of this study are needed to assure the long-term benefits of LA insulin agents.
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校內：2022-07-21公開校外：2022-07-21公開