Peripheral artery disease and aortic complications in type 1 and type 2 diabetes mellitus

Abstract

Background: The connection between diabetes mellitus and atherosclerotic cardiovascular disease (ASCVD) complications, such as myocardial infarction and stroke, is well-established. However, the nature and extent of the relationship between diabetes mellitus and non-coronary vascular conditions, including lower extremity peripheral artery disease (PAD) and aortic diseases, are less clear. Aims and Methods: In this thesis, type 1 and type 2 diabetes cohorts, respectively, were identified from the Swedish National Diabetes Register (NDR), and NDR data were linked to data from other Swedish health registries. This comprehensive data linkage facilitated the gathering of detailed information on comorbidities, medication usage, socioeconomic factors, outcomes, and mortality. To thoroughly address the research questions, the thesis employed an array of statistical techniques, ranging from traditional survival analysis methods to advanced machine learning models. The objectives of the thesis were to: 1) examine the risks of lower extremity PAD within the framework of managing ASCVD risk factors among persons with type 1 and type 2 diabetes, respectively and, with exploratory comparisons of these risks with the risks found in controls without diabetes; 2) to assess the specific contribution of different risk factors to the statistical models for outcome risks among persons with diabetes; 3) to evaluate mortality risks in persons with type 2 diabetes who also suffer from lower extremity PAD; 4) and to explore the risks of aortic diseases in persons with type 1 and type 2 diabetes, respectively, compared with controls free of diabetes from the general population. Results: For both persons with diabetes type 1 as well as those with type 2 diabetes, a graded increase in risk of lower extremity PAD is present for each additional ASCVD risk factor that does not reach guide-line recommended target levels. Particularly, persons with diabetes (covering both types of diabetes) who do not meet target levels for any of the analyzed ASCVD risk factors face the highest increased risk of lower extremity PAD compared with controls without diabetes. Traditional ASCVD risk factors are the most significant contributors to the statistical models for PAD risks among both diabetes groups. Mortality risks are elevated in those with both type 2 diabetes and PAD, compared with those with PAD alone. An inverse association between aortic diseases and both types of diabetes mellitus were observed. Conclusions: A strong, graded relationship exists between the level of ASCVD risk factor management and the risk of incident lower extremity PAD among persons with diabetes, suggesting that intensive ASCVD risk factor management may reduce PAD risk. Additionally, it was observed that persons with type 2 diabetes and PAD face very high mortality risks. These findings debate for the importance of intensive and optimized ASCVD risk factor management strategies in persons with diabetes. The inverse association between both types of diabetes and aortic diseases calls for further research to uncover the mechanisms at play.