探討非阻塞性睡眠障礙族群使用苯二氮平類藥物發生第二型糖尿病潛在風險

Potential Risk of Type 2 Diabetes Mellitus in Nonapnea Sleep Disorders Patients with Benzodiazepines

張詠婕(Yong-Chieh Chang)

指導教授 ： 楊奕馨

高雄醫學大學/藥學院/藥學系碩士在職專班/碩士(2016年)

摘要

研究背景
睡眠障礙在文明社會中是很常見的問題之一，不僅影響到情緒、工作、學習的專注力，更可能影響身體健康狀況。目前有文獻指出非阻塞型睡眠障礙 (Nonapnea sleep disorders, NSDs)可能增加第二型糖尿病發生風險；而Benzodiazepines (BZDs)為常見的鎮靜安眠藥之一，常用於睡眠障礙的患者，另有研究指出非阻塞型睡眠障礙之病人使用BZDs與第二型糖尿病發生風險的增加有關，然其研究結果中缺乏對於使用BZDs類助眠藥物之種類、劑量等與第二型糖尿病發生風險影響的進一步評估。
研究目的
針對NSDs病人且使用BZDs者，分析此類族群病人使用不同種類BZDs、使用天數、使用累積劑量等與第二型糖尿病風險之關聯性。
研究方法
本研究利用台灣健保資料庫2005年百萬歸人檔，進行回溯性追蹤研究分析，主要將使用BZDs之NSDs病人分為：1)使用長效組BZDs；2)使用中短效組BZDs，以Time-dependent Cox Proportional Hazard model於兩組BZDs中，分別以年齡、性別、Charlson Comorbidities分數、BZDs累積劑量、BZDs累積使用天數等相關變項進行風險分析，探討中短效組BZDs及長效組BZDs與第二型糖尿病風險發生之相關性。
研究結果
1997年1月1日至2001年12月31日間共擷取符合條件的39,044位病人，平均追蹤8.25年，其中，中短效組BZDs為33,145人(84.9%)，長效組BZDs為5,899人(15.1%)。整體而言，長效組BZDs對於第二型糖尿病發生風險，顯著的低於中短效組BZDs (adjusted HR=0.82, 95% CI=0.76-0.88)，而使用累積天數≦180天者，與中短效組BZDs相比亦有較低的第二型糖尿病發生風險(adjusted HR=0.72, 95%CI=0.65-0.79)。
結論
非阻塞性睡眠障礙族群使用BZDs治療者，長效組BZDs對於第二型糖尿病的發生風險顯著的低於中短效組BZDs，特別是累積使用天數≦180天以及使用長效型Diazepam者，更見顯著效益。

關鍵字

非阻塞性睡眠障礙 ； 第二型糖尿病 ； 苯二氮平 ； 台灣健保資料庫

並列摘要

Background：
Sleep disorders are one of the common conditions in our modern society. They affect our daily function, mental and physical health in many ways. Several studies have investigated the association of Nonapnea sleep disorders (NSDs) with the risk for diabetes mellitus (DM) development. Benzodiazepines (BZDs) are one of the most often used hypnotics treatment for NSDs. Although one study has reported an increased risk of Type 2 DM in NSDs patients using BZDs, but there is lack of information of dose-response effects on BZDs such as cumulative using days, cumulative doses or the classification of BZDs.
Objective：
Our study aim was to assess NSDs patients who were prescribed BZDs as treatment and their potential risk to type 2 DM while considering classification of BZDs, cumulative using days of BZDs and cumulative doses of BZDs.
Method：
This is a retrospective cohort study. We used the Longitudinal Health Insurance Database 2005 (LHID2005). Patients were classified into two groups: long acting BZDs and intermittent short acting BZDs (as the reference). We used Cox proportional hazard regression analysis with time-dependent covariates to analyze the risk of long acting BZDs compared with intermittent short acting BZDs after adjusting covariates of age, gender, Charlson Comorbidites Score, cumulative BZDs using days and cumulative BZDs defined daily doses and the potential risk of type 2 DM.
Results：
We identified 39,044 patients with newly diagnosed NSDs from January 1, 1997 to December 31, 2001 and under BZDs treatment as our study cohort. The average follow-up time was 8.25 years. These patients were further divided into two separated groups of BZDs: 33,145 (84.9%) patients were in the group of intermittent short acting of BZDs and 5,899 (15.1%) patients were in the group of long acting BZDs. Overall, patients in the group of long acting BZDs had a lower risk of type 2 DM (adjusted HR=0.82, 95% CI=0.76-0.88) compared with patients in the intermittent short acting group. In addition, patients with cumulative usage of 1-180 days had a lower risk of type 2 DM (adjusted HR=0.72, 95%CI=0.65-0.79).
Conclusion：
Patients with NSDs under BZDs had a lower risk of Type 2 DM in the group of long acting BZDs compared with patients in the group of intermittent short acting BZDs, particularly for patients with cumulative usage of 1-180 days and Diazepam users.

並列關鍵字

Nonapena sleep disorders ； Type 2 diabetes mellitus ； Benzodiazepines ； Taiwan National Health Insurance Research Database

參考文獻

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