Circulating Levels of erythrocytes-derived vesicles are associated with glucose control in type 2 diabetes mellitus patients with atrial fibrillation
Authors: Berezin A E , Obradovic Z , Berezina T A , Kopp K , Hoppe U , Lichtenauer M , Wernly B , Berezin O O 
Published: June 2024

Abstract

Background
Previous studies demonstrated that insulin resistance, hyperglycemia contribute to the development of a pro-thrombotic state characterized by increased platelet activation, activation of coagulation cascade and elevated number of extracellular vesicles (EVs) in type 2 diabetes mellitus (T2DM) patients. There is a less known impact of glycaemia control in T2DM patients with concomitant heart failure (HF) and atrial fibrillation (AF) on a number of erythrocytes-derived EVs. The aim of the study was to elucidate whether glucose control in T2DM patients with HF and AF affect a circulating number of erythrocytes-derived EVs.

Methods
The entire patient population composes of 417 patients (231 male, 55.4% and 186 female, 44.6%) with average age of 53 years as well as 25 healthy volunteers and 30 T2DM non-HF individuals. As inclusion, age ≥ 18 years, T2DM, established HF, and written consent to participate in the study was used. Patients after successful ablation procedure (mainly radiofrequency ablation) were included in the group non-AF in 6 weeks after procedure if cardiac rhythm is sinus. All patients were divided into two groups depending on criteria of poor glycemic control (HbA1c &lt; 6.9% and ≥7.0%, respectively). Hemodynamics features, conventional biochemistry parameters and EVs measure were performed at the baseline. Flow cytometry was performed according to conventional protocol with FMO standards to detect and measure EVs.

Results
Circulating levels of CD235a+ PS+ erythrocytes-derived vesicles differed amongst T2DM patients depending on HF presentation when compared with healthy volunteers (Figure 1). Figure 2 illustrated the differences in circulating amount of CD235a+ PS+ RBC-derived vesicles in AF and non-AF patients with T2DM and HF depending on glycaemia control. There were significantly lower levels of CD235a+ PS+ RBC-derived vesicles were detected in those with HbA1c &lt; 6.9% than in patients with HbA1c ≥ 7.0%. To note, there were no significant differences in circulating amount of CD235a+ PS+ erythrocytes-derived vesicles between patients in entire cohort (p = 0.24) and in non-AF sub-cohort (p = 0.40) with HbA1c &lt; 6.9% and HbA1c ≥ 7.0%, respectively. The Receive Operation Characteristics curve analysis revealed that the well-balanced cut-off point for circulating amount of CD235a+ PS+ erythrocytes-derived vesicles (HbA1c ≥ 7.0% versus HbA1c &lt; 6.9%) were 545 particles in µL (area under curve = 0.91, sensitivity = 74.2%, specificity = 90.3%; p = 0.0001). Multivariate linear regression yielded that NT-proBNP (OR = 1.07; 95% CI = 1.02–1.10, p = 0.04) and CD235a+ PS+ erythrocytes-derived vesicles ≥ 545 particles in µL (OR = 1.06; 95% CI = 1.01–1.11, p = 0.044) remained independent predictors for HbA1c ≥ 7.0%.

Conclusion
Poor glycaemia control is associated with elevated levels of CD235a+ PS+ EVs, which were found to be independent predictor for AF presentation in T2DM patients with HF. Circulating levels of EVs EVs in AF and non-AF patients