The paradoxical protective effect of diabetes on abdominal aortic aneurysms, clinical and epidemiological studies

Abdominal aortic aneurysm (AAA) is a common disease with dilatation of the infrarenal aorta above 50% corresponding to an infrarenal aorta ≥30 mm. AAAs have a prevalence of 2-3% in men above 60 years of age, and 6-8 times lower in women. An AAA was traditionally seen as atherosclerotic disease, and the has risk factors were assumed to apply such as smoking, hypertension and diabe-tes. Studies found, however, that the presence of diabetes reduced the risk of having an AAA by almost half. This PhD thesis aimed to explore the association between the paradoxical, protective effect of diabetes on development, growth and rupture of AAAs (RAAA).

We conducted four studies. First, a register-based case-control study of the Danish population from 1998 to 2013 to estimate the association between long-term use of metformin and the risk of RAAA. Second, an analysis of a randomised population-based screening trial in Danish men aged 65-74 years to estimate the association between glycated haemoglobin, HbA1c, and the growth rate of AAAs. Third, an analysis of two randomised population-based screening trials in Danish men aged 65-74 years to estimate if the paradoxical, protective effect of diabetes on the development of AAA persists in Danish men. Furthermore, a meta-analysis of population-based screening studies to visualise the potential change over time. Fourth, a register-based case-control study of the Danish population from 1996 to 2016 to estimate the association between diabetes and RAAA.

We found that long-term use of metformin did not affect the risk of RAAA among people with dia-betes. We found that elevated levels of HbA1c reduced the growth of AAA both in the total popula-tion but interestingly also for men without diabetes. In the analyses of the two Danish screening studies, we found that diabetes was associated with a significantly lower odds ratio (OR) of AAA in the early screening trial (2008-2011), but not in the latter (2014-1018). In our meta-analysis, we found that the crude OR of having AAA and the presence of diabetes increased over time, but the adjusted OR remained unchanged. Lastly, we found no effect of diabetes regarding the risk of hav-ing RAAA, given the presence of a large AAA.

In conclusion, we were not able to show an effect of metformin or diabetes in general on the risk of RAAA, nor a change over time in the independent effect of diabetes in our adjusted meta-analysis, but we demonstrated that the level of HbA1c is of importance. Overall, although the independent effect of diabetes is unchanged, people are complex with multiple diseases, and we should no long-er consider people with diabetes protected against AAAs.