Clinical risk phenotypes in diabetes and their associations with adverse cardiovascular events. a report from the silesia diabetes-heart project

Aims: Diabetes is characterized by clinical heterogeneity. This study aimed to identify different clinical phenotypes of real-world people with diabetes and to assess their associations with major adverse cardiovascular events (MACEs). Methods: From a prospective Polish registry of people with diabetes, hierarchical cluster analysis was performed based on 19 variables, including co-morbidities and cardiovascular (CV) risk factors. The primary outcome was the risk of MACEs (CV death, acute coronary syndrome and myocardial revascularizations, ischaemic stroke, new onset heart failure, and hospitalization for CV reasons). Secondary exploratory outcomes were each MACE component and all-cause death. Results: On 2109 participants (median age 60 years, interquartile range [IQR] 45-69, 51.3% men) included, three different phenotypes were identified: (i) cluster 1 (27.8%) - young with type 1 diabetes; (ii) cluster 2 (42.0%) - elderly with type 2 diabetes and high complexity; (iii) cluster 3 (30.2%) - middle-aged with type 2 diabetes and cardiometabolic risk factors. Compared to cluster 1, the risk of primary outcome was higher for clusters 2 and 3 (adjusted hazard ratio [aHR] 2.93, 95% CI 1.60-5.36, and aHR 1.85 95% CI 1.07-3.20, respectively). Using cluster 3 as the reference, cluster 1 was associated with a lower risk (aHR 0.54, 95% CI 0.31-0.94), and cluster 2 with a higher risk (aHR 1.58, 95% CI 1.08-2.33). Conclusions: People with diabetes aggregate into different clinical phenotypes, each with different risks of MACEs. Integrated approaches tailored to these diverse clinical profiles are needed to improve outcomes in this heterogeneous and multifaceted disease.