糖尿病患者使用口服糖尿病藥物與結核病或慢性肺阻塞性肺病的關係之探討

研究背景： 糖尿病 (DM) 在全球已有極高的盛行率以及較為龐大醫療負擔。現今的研究也指出，DM 對於慢性肺病的發炎反應甚至是肺癌有極高的相關性。慢性肺病如慢性阻塞性肺病 (COPD) 及肺結核 (TB) 在全球有較高的死亡率，也證實 DM 也是 COPD 及 TB 的風險因子。我們好奇，是否糖尿病病人使用口服糖尿病用藥後，對於慢性肺病的風險是否下降，提供臨床醫療的用藥上更多的選擇及方向。 研究方法：本研究主要的資料來源為國家衛生研究院所提供的全民健康保險資料庫 (NHIRD) 中的承保抽樣歸人檔 (LHID2010) 。本篇研究選取了五種常見的口服糖尿病用藥：sulphonylureas、biguanides、 meglitinides、α-glucosidase inhibitors、thiazolidinediones (TZDs) 。探討在糖尿病的病人中使用五種口服 DM用藥後與慢性肺病的關係。 (1)在研究 TB 的風險中，我們使用了巢式病例對照研究，經由配對後，利用卜瓦松迴歸模型(Poisson Regression Model)進行分析。探討五種口服 DM 用藥對於疾病之間風險。(2)在研究 COPD 的風險中，我們使用了回溯性研究，經由配對後，利用存活曲線(Kaplan-Meier curve)及比例風險模式(Cox proportional hazard model)進行分析。 研究結果：第一篇探討 TB 的研究中，研究對象共有 1556 位個案，以及 6224位的配對組，經由配對調整後分析發現，使用低濃度的 α-glucosidase inhibitor的發生率比 (Incidence Rate Ratio, IRR) 為 0.810 (95% 信賴區間[CI]: 0.693-0.948)，使用高濃度的 α-glucosidase inhibitor 的 IRR 為 0.805 (95% CI: 0.651-0.995)。更進一步在 α-glucosidase inhibitor 使用者中進行分析，高濃度的α-glucosidase inhibitor 的 IRR 為 0.918 (95% CI: 0.854–0.987)，高濃度的sulphonylurea IRR 為0.753 (95% CI: 0.635–0.892)。第二篇探討COPD 的研究中，研究對象共有 2056 位 DM 病人，其中使用口服 DM 用藥有 1028 人，配對組有1028 人，經由調整後分析發現，對於 COPD 的風險，使用 α-glucosidase inhibitor的 HR 為 1.697 (95% CI: 1.208-2.383)。更進一步與其對照組進行分析，使用α-glucosidase inhibitor 的風險比(Hazard Ratio, HR)為 2.295( 95% CI: 1.304–4.038)。 研究討論：在 DM 病人中，使用 α-glucosidase inhibitor 會增加罹患 COPD 的風險，但是卻會降低罹患 TB 的風險，這一個很有趣的結果。本研究結果可提供臨床用藥上的參考，針對不同的慢性肺病，提升 DM 病人的用藥安全及更多選擇。

Background: Diabetes (DM) has a very high prevalence rate and a large medical burden in the world. Current research also points out that DM has a very high correlation with the inflammatory response of chronic lung disease and even lung cancer. For example, chronic obstructive pulmonary disease (COPD) and tuberculosis (TB) have high mortality worldwide, and DM is also a risk factor for COPD and TB. We are curious as to whether the risk of chronic lung disease for diabetic patients after taking oral DM medication. Provide more choices and directions for clinical medical use. Method: The main data source of information for this study was the Longitudinal Health Insurance Database (LHID2010) in the National Health Insurance Research Database (NHIRD). In this study, five common oral DM medications were selected: sulphonylureas, biguanides, meglitinides, α-glucosidase inhibitors, and thiazolidinediones (TZDs). To explore the relationship between the use of five oral DM medications in patients with DM and chronic lung disease. (1) In the study of the risk of COPD, we used a retrospective study, and after matching, the Kaplan-Meier curve and the Cox proportional hazard model were used for analysis. (2) In the study of TB risk, we used a nested case-control study, which was matched and analyzed by the Poisson Regression Model. Result: In the first study of COPD, we extracted 2056 diabetic patients, including 1028 oral DM medications users and 1028 matched control patients. After adjustment analysis, the Hazard Ratio (HR) of α-glucosidase inhibitor was 1.970 (95% CI: 1.208-2.383). Further analysis with the control group, the HR of the α-glucosidase inhibitor was 2.295 (95% CI: 1.304-4.038). In the second study of TB, we extracted 1556 cases and 6224 matched controls. After adjustment analysis, the Incidence Rate Ratio (IRR) of low-concentration of α-glucosidase inhibitor users were 0.810 (95% CI: 0.693-0.948) for TB, the IRR of high- concentration α-glucosidase inhibitor were 0.805 (95% CI: 0.651-0.995). Further analysis of the α-glucosidase inhibitor users, the IRR of high- concentration α-glucosidase inhibitor users were 0.918 (95% CI: 0.854- 0.987), the IRR of high-concentration sulphonylurea users were 0.753 (95% CI: 0.635–0.892). Conclusion: In diabetic patients, the use of alpha-glucosidase inhibitors increases the risk of developing COPD but reduces the risk of developing TB. This was a very interesting result. It could improve the safety and more choices of DM patients for different chronic lung diseases.