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| 研究生： |
李宗穎 Lee, Tsung-Ying |
|---|---|
| 論文名稱： |
利用台灣健保資料庫比較第一型糖尿病病患使用長效胰島素和中效胰島素在糖尿病急、慢性併發症和死亡的風險 Comparative Risks of Diabetes Complications and All-Cause Mortality of Long- versus Intermediate-acting Insulin in Patients with Type 1 Diabetes: A Population-based Study 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： | 2016 |
| 畢業學年度： | 105 |
| 語文別： | 中文 |
| 論文頁數： | 128 |
| 中文關鍵詞： | 台灣 、第一型糖尿病 、長效胰島素 、胰島素類似物 、糖尿病併發症 、死亡 、發生率 、盛行率 、相對療效 |
| 外文關鍵詞： | Taiwan, Type 1 diabetes, long-acting insulin, insulin analogue, diabetes complication, all-cause mortality, incidence, prevalence |
| 相關次數： | 點閱：104 下載：4 |
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第一型糖尿病的治療目標是減緩或避免急、慢性併發症的發生，已知加強胰島素治療能夠降低糖化血色素，進而減緩小血管及大血管併發症的發生，但同時也增加了低血糖的風險。治療第一型糖尿病的胰島素策略是模擬正常人的胰島素分泌狀況，長效胰島素近似於正常人空腹時所需的基礎胰島素，相較於中效胰島素能提供較穩定的藥效特性以及較小的血糖波動，雖然降低糖化血色素的幅度相當，卻能減少低血糖的風險，但目前對長期併發症的相對療效了解非常有限。
研究目的
本研究有二個研究目的，第一，估計第一型糖尿病病人急、慢性併發症的盛行率與發生率；第二，估計第一型糖尿病病人使用長效和中效胰島素在慢性併發症（包括腎病變、視網膜病變、神經病變、心血管疾病）、急性併發症（包括住院高血糖、輕微低血糖、住院低血糖）和死亡的風險比。
研究方法
本研究分成兩部分進行，一是第一型糖尿病併發症之流行病學，二是基礎胰島素對於第一型糖尿病併發症之療效比較，皆使用台灣健保資料庫（涵蓋率高達98.6%）進行研究分析。
流行病學部分，篩選出2000-2013年之第一型糖尿病病人，計算各項急、慢性併發症的年度盛行率、發生密度以及依據糖尿病病程之累積發生率。
療效比較部分，篩選出2004-2008年間第一次使用基礎胰島素的第一型糖尿病病人，並根據起初穩定使用的基礎胰島素處方分成長效 (insulin glargine/detemir) 和中效胰島素 (NPH/lente/ultralente) 兩組。本研究使用Cox proportional hazards models和inverse probability of treatment weights控制干擾因子並估計風險比。觀察區間從2004年一直持續到2013年。療效和安全性之觀察結果包括腎病變、視網膜病變、神經病變、心血管事件、住院高血糖、輕微低血糖、住院低血糖、任何低血糖、任何併發症和死亡。胰島素處方日數及糖化血色素測量次數在研究中設為時間相依共變數。另執行三個敏感性分析，包括將intention-to-treat analysis改為on treatment analysis、更改穩定處方胰島素的定義以及更改第一型糖尿病的定義。
研究結果
流行病學部分，2000-2013年共1,635位第一型糖尿病病人 (prevalent cases)，其中在研究區間內新發生的糖尿病病人共1,579位。盛行率方面，住院高血糖的盛行率在2000-2013間呈現下降趨勢，心血管事件、腎病變、視網膜病變、神經病變以及輕微低血糖的盛行率則是呈現上升趨勢，其中以視網膜病變的上升幅度最大，住院低血糖的盛行率則在2005年之後呈現穩定。發生率方面，在12年的研究觀察區間，心血管事件、腎病變、視網膜病變、神經病變、住院高血糖、輕微低血糖以及住院低血糖之發生密度依序為0.28、2.13、4.53、1.89、7.40、4.07和0.97 (per 100 person-years)；依據第一型糖尿病之病程觀察併發症之累積發生率，心血管事件在12年後達到5%、腎病變在12年後達到23%、視網膜病變在13年後達到43%、神經病變在11年後達到18%、住院高血糖在11年後達到42%、輕微低血糖在13年後達到37%、住院低血糖在12年後達到10%。
療效比較部分，研究對象共納入594人，長效胰島素組 (insulin glargine / detemir) 190人、中效胰島素組 (NPH) 404人，平均年齡分別為18.79歲和12.25歲，糖尿病病程分別為1.17年和1.09年。長效比起中效胰島素組的校正後風險比，在心血管事件為0.26 (95% CI, 0.07-1.03)、腎病變為0.87 (95% CI, 0.66-1.15)、視網膜病變為0.78 (95% CI, 0.65-0.93)、神經病變為0.57 (95% CI, 0.39-0.83)、住院高血糖為0.96 (95% CI, 0.79-1.16)、輕微低血糖為0.33 (95% CI, 0.27-0.41)、住院低血糖為1.06 (95% CI, 0.71-1.58)、任何低血糖為0.44 (95% CI, 0.36-0.53)、任何併發症為0.65 (95% CI, 0.57-0.74)、死亡率為1.70 (95% CI, 0.71-4.07)。敏感性分析呈現相似的結果。
研究結論
在臨床實務執行的情況下，第一型糖尿病病人選用長效胰島素治療有較低的視網膜病變、神經病變以及輕微低血糖的風險。本研究亦觀察到長效胰島素可能可以減緩腎病變和心血管事件的發生，值得設計十年以上的觀察區間做進一步的研究。
Long-acting insulin analogues have similar HbA1c lowering values but lower risk of hypoglycemia compared with intermediate-acting insulin due to its improved time-action profile, but knowledge about comparative efficacy/effectiveness of chronic complications of long- versus intermediate-acting insulin is limited. This study aimed to estimate the incidence and prevalence rate of diabetes complication and to evaluate the hazard ratios of long- versus intermediate-acting insulin regarding acute (hyperglycemia and hypoglycemia) and chronic (nephropathy, retinopathy, neuropathy and cardiovascular disease) complications and all-cause mortality.
We use Taiwanese National Health Insurance Research Database to identify patients with Type 1 diabetes from 2000 to 2013 for estimation of epidemiology of complications and also to identify a cohort with Type 1 diabetes who receive basal insulin for the first time from 2004 to 2008 to conduct a comparative effectiveness study. In the part of comparative effectiveness, individuals are divided into long-acting insulin group (insulin glargine/detemir) and intermediate-acting insulin (NPH/lente/ultralente) group by the type of basal insulin at the initial treatment regimens. In this cohort of 594 patients, 190 patients were classified as long-acting insulin group and 404 patients were classified as intermediate-acting insulin group (all of them were NPH users). The mean age of each group were 18.79 and 12.25 years, and the duration of diabetes were 1.17 and 1.09, respectively. The patients were followed until 31 December 2013. Compare with intermediate-acting insulin, long-acting insulin was associated with reduced risk of retinopathy (HR 0.78, 95% CI 0.65-0.93), neuropathy (HR 0.57, 95% CI 0.39-0.83) and mild hypoglycemia (HR 0.33, 95% CI 0.27-0.41) in patients with Type 1 diabetes.
Key words: Taiwan; Type 1 diabetes; long-acting insulin; insulin analogue; diabetes complication; all-cause mortality; incidence; prevalence
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校內：2022-01-31公開校外：2022-01-31公開