Diabetic Retinopathy and Skin Tissue Advanced Glycation End Products Are Biomarkers of Vascular Events in Type 2 Diabetic Patients
Abstract BACKGROUND AND AIMS: Vascular events are the main cause of mortality in patients with type 2 diabetes. However, the risk of vascular events is not homogeneous in subjects with type 2 diabetes and, therefore, an early identification of patients at high risk of developing vascular events remains a challenge to be met. The aim of this study is to evaluate whether the presence of diabetic retinopathy (DR) and accumulation of advanced glycation end products (AGEs) in subcutaneous tissue can help to identify those patients at high risk of vascular events.MATERIAL AND METHODS: It was a prospective study comprising 200 subjects with type 2 diabetes with no history of clinical cardiovascular disease and 60 non-diabetic controls, matched by age and sex (PRECISED study: ClinicalTrials.gov NCT02248311). The inclusion period began on September 2014 and finished on June 2017. We collected basal features of the subjects, classical cardiovascular risk factors (i.e. age, sex, hypertension, dyslipidemia and coronary artery calcium score [CACs]), presence and degree of DR, and the accumulation of AGEs in subcutaneous tissue using the AGE readerTM device (DiagnOptics Technologies). We followed these subjects until December 2020, collecting any coronary, cerebrovascular or peripheral arterial event.RESULTS: After a follow up of 4.35 ± 1.43 years, a total of 24 vascular events were registered. There was no significant difference regarding age and gender between individuals with type 2 diabetes and the control group. The number of vascular events was higher in type 2 diabetes group than in the control group (12.3% vs. 1.75%). When analysing the risk factors we found that apart from classic risk factors such as age, gender and CACs, subjects with type 2 diabetes and vascular events presented a higher prevalence of DR (47.8% vs. 24.4%; p = 0.018) and AGEs in subcutaneous tissue (63.15% vs 26.71% of values in the higher tertile, p = 0.001). DR and AGEs in subcutaneous tissue remain as independent variables related to the development of vascular events in the Cox proportional hazard multiple regression analysis (HR 2.58, 95%CI 1.14–5.85, p = 0.023, and HR 4.68, 95%CI 1.83–11.96, p = 0.001; respectively).CONCLUSIONS: As we expected, patients with type 2 diabetes have significantly more VE than non-diabetic subjects. Apart from the classic factors such as age, sex and CACs, we observed that the presence of DR and high levels of AGEs in subcutaneous tissue were predictors of vascular events.