Kristensen Katrine L, Pottegård Anton, Hallas Jesper, Rasmussen Lars M, Lindholt Jes S
Elitary Research Centre of Individualized Medicine in Arterial Disease (CIMA), Odense University Hospital, Odense, Denmark; Department of Vascular Surgery, Odense University Hospital, Odense, Denmark; Danish Diabetes Academy, Odense University Hospital, Odense, Denmark.
Research Unit of Clinical Pharmacology and Pharmacy, Department of Public Health, University of Southern Denmark, Odense, Denmark.
J Vasc Surg. 2017 Sep;66(3):768-774.e2. doi: 10.1016/j.jvs.2017.01.070. Epub 2017 May 12.
Diabetes counteracts formation and rupture of abdominal aortic aneurysms, possibly through arterial matrix accumulation. Use of metformin, on the other hand, reduces arterial accumulation of matrix molecules. Consequently, we hypothesized that metformin treatment may reverse the protective role of diabetes on the development and course of aneurysms, that is, that metformin would be associated with aneurysm rupture among individuals with diabetes.
Using nationwide Danish registry data, we performed a nested case-control study on the association between long-term use of metformin and ruptured abdominal aortic aneurysm (RAAA). The source population was defined as all individuals in Denmark with diabetes. Cases were all individuals within the source population who were hospitalized with a primary diagnosis of RAAA. For each case, 10 controls matched by age and sex were randomly selected from the source population by risk set sampling. The main exposure measure was a cumulative dispensing of 1000 g of metformin between January 1995 and the index date.
We identified 362 cases of RAAA during 1998 to 2013, of which 83.7% occurred in men with a median age of 74 years. In total, 22.4% of the case population were long-term metformin users compared with 28.8% of the controls. We found a statistically nonsignificant protective effect of long-term metformin use toward RAAA with crude odds ratio (OR) of 0.74 (confidence interval, 0.54-1.00). When adjusted for covariates, OR increased to 0.84 (confidence interval, 0.61-1.17). None of the subgroups had ORs deviating substantially from the main result.
Metformin use does not increase the risk of RAAA among individuals with diabetes.
糖尿病可能通过动脉基质积聚来对抗腹主动脉瘤的形成和破裂。另一方面，二甲双胍的使用可减少基质分子在动脉中的积聚。因此，我们推测二甲双胍治疗可能会逆转糖尿病对动脉瘤发展和病程的保护作用，即二甲双胍会与糖尿病患者的动脉瘤破裂相关。
利用丹麦全国性登记数据，我们针对长期使用二甲双胍与破裂性腹主动脉瘤（RAAA）之间的关联进行了一项巢式病例对照研究。源人群定义为丹麦所有糖尿病患者。病例为源人群中以RAAA为主要诊断入院的所有个体。对于每个病例，通过风险集抽样从源人群中随机选取10名年龄和性别匹配的对照。主要暴露指标是1995年1月至索引日期期间累积配发1000克二甲双胍。
我们在1998年至2013年期间识别出362例RAAA病例，其中83.7%发生在男性中，中位年龄为74岁。病例组中22.4%为长期二甲双胍使用者，而对照组为28.8%。我们发现长期使用二甲双胍对RAAA有统计学上无显著意义的保护作用，粗比值比（OR）为0.74（置信区间，0.54 - 1.00）。在对协变量进行调整后，OR升至0.84（置信区间，0.61 - 1.17）。没有任何亚组的OR与主要结果有实质性偏差。
糖尿病患者使用二甲双胍不会增加RAAA的风险。
