探討氫離子幫浦抑制劑對有腸胃疾病患者罹患糖尿病風險性的影響

Exploring the impact of proton pump inhibitors on the risk of diabetes in patients with gastroenterologic disorders

蕭羽婷(Yu-Ting Hsiao)

指導教授 ： 王莉萱

共同指導教授 ： 林秀真

臺北醫學大學/藥學院/生技製藥企業經營管理產業碩士專班/碩士(2014年)

摘要

背景和目的

糖尿病是世界主要的慢性疾病，而現在患有糖尿病的人數比起30年前已增加一倍以上。2013年，糖尿病列為台灣十大死因第五位。而Proton pump inhibitors (PPIs)是一種抑制氫離子幫浦的藥物這種藥物可以減少胃酸分泌，用於治療胃酸相關疾病，它主要抑制 H+/K+ATPase，進而導致胃泌素濃度增加。有文獻顯示PPIs可以改善糖尿病病患之血糖控制，此外，有相關動物實驗發現胃泌素會誘導β細胞新生，在體外實驗也發現胃泌素會增加β細胞的質量，由於至今仍缺乏探討PPIs與糖尿病風險之間相關性的臨床試驗，尤其是針對亞洲人的研究，因此我們執行了這項在台灣的回溯性世代研究，以比較使用PPIs及未使用PPIs之腸胃道疾病患者罹患糖尿病的風險。

研究方法

本研究納入338,098位腸胃道疾病患者，分析資料取樣自國家衛生研究院所提供之全民健康保險資料庫承保抽樣歸人檔 (Longitudinal Health Insurance Database, LHID2000), 篩選自2000年1月1日至2006年12月31日有三次以上確診為腸胃道疾病患者，並且納入2000年1月1日前未被診斷罹患糖尿病以及未使用Proton Pump Inhibitor類藥物，以確保所納入之病人皆為新診斷的案例，我們將腸胃道疾病患者分為以下組別:使用PPIs者 (研究組);未使用PPIs (比較組1)，以及非腸胃道疾病患者 (比較組2)，對照組則使用SAS軟體隨機選取二位未使用PPIs之腸胃道疾病患者，來與一位有使用PPIs之腸胃道疾病患者配對；未使用PPIs腸胃道疾病患者與2位非腸胃道疾病患者做配對。
研究結果

沒有使用PPIs藥物的腸胃道疾病患者相較於非腸胃道疾病患者罹患糖尿病的校正後風險比為1.27 (95% CI 1.19-1.36; p < 0.001) ；有使用PPIs藥物的腸胃道疾病患者相較於沒有使用PPIs藥物的腸胃道疾病患者罹患糖尿病校正後風險比為0.73 (95% CI 0.67-0.80; p < 0.001)。此外，分析PPIs使用劑量對於糖尿病風險的影響，發現具有顯著的劑量效應 ( p值趨勢檢定< 0.001)。

結論

本研究指出PPIs可能可以降低腸胃道疾病患者罹患糖尿病的風險，並且具有顯著的劑量效應。但目前仍需有更多的研究來加以佐證，以驗證PPIs是否用於臨床上當作新的抗糖尿病藥物或是做為預防罹患糖尿病的用藥。

關鍵字

氫離子幫浦抑制劑 ； 糖尿病

並列摘要

Background and objective
Diabetes mellitus (DM) is an epidemic disease worldwide, the number of people with diabetes mellitus has more than doubled globally in the past three decades. In 2013, diabetes mellitus (DM) was the number five killer inTaiwan. Proton pump inhibitors (PPIs) are now widely used for the treatment of gastric acid-related diseases. It acts to block the hydrogen/potassium adenosine triphosphatase enzyme in the system ,and thereby resulting in increased blood gastrin concentration. Several studies have shown that PPIs are associated with better glycemic control in DM patients. In addition, gastrin induces β-cell neogenesis, and in vitro studies, this hormone increases the β-cells mass. There is limited clinical data regarding the PPIs effects on DM risk, especially among Asian population, and these studies did not provide a clear analysis of the effect of PPIs dose on DM risk reduction, we conducted a hypothesis-generating, retrospective study in Taiwan to assess the risk of DM development among Gastrointestinal Disease (GID) patients treated with PPIs.

Methods
The study included 338,098 GID patients identified from the Longitudinal Health Insurance Database, with at least three consecutive episodes of diagnosed GID between January 1, 2000 and December 31, 2006. Only patients who had not been diagnosed with DM and received PPIs before January 1, 2000 were included to ensure that only newly identified cases were included. We classified the GID patients into the following groups: patients who received PPIs (study group), patients who did not received PPIs (comparison group I)；and non-GID patients (comparison group II).
SAS statistical program was used to identify and select patients in the study group who were then matched to two GID patients without PPIs (comparison group I) and each patient in comparison group I was matched to two non-gastrointestinal disease patients.

Results
We compared the DM risk between comparison group I and comparison group II, the adjusted hazard ratio was 1.27 (95% CI 1.19-1.36; p < 0.001) for GID patients without PPIs (comparison group I) compared with non-GID patients (comparison group II). In addition, the adjusted hazard ratio was 0.73 (95% CI 0.67-0.80; p < 0.001) for GID patient receiving PPIs (study group) compared with GID patient without PPIs (comparison group I). In addition, the effects of PPIs were shown to be significantly dose-dependent (P for trend < 0.001).

Conclusions

The results showed decrease DM risk in GID patients associated with use of PPIs and the association appears to be significantly dose-dependent. Further studies are warranted to determine if this association is causal and whether PPIs have the potential to be used clinically as new antidiabetic drugs and DM prevention agents.

並列關鍵字

proton pump inhibitors ； diabetes mellitus

參考文獻

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