Effect of dapagliflozin on the structural and functional properties of arterial vessels in patients with type 2 diabetes mellitus in combination with obesity

Abstract

Modern trends in the treatment of type 2 diabetes mellitus (DM) should include not only the normalization of carbohydrate metabolism disorders, but also a possible positive effect on the cardiovascular system. The use of the drug dapagliflozin for several years has proven to reduce the manifestations of heart failure. However, the possible significance of dapagliflozin in the reversal of structural and functional changes in the arteries in patients with type 2 DM and obesity has not been studied enough. The aim of the study was to establish the possibility of correction of structural and functional disorders of arterial vessels in patients with type 2 DM in combination with excess body weight (EBW) and obesity with dapagliflozin as part of complex therapy. Material and methods. 99 people were examined, including 71 patients with diabetes mellitus, the DM (type 2) diagnosis was verified according to the primary documentation. All patients provided written informed consent to participate in the study. Among the patients, the first group consisted of 36 people (14 women and 22 men) with EBW and obesity (body mass index >25), average age 55.91 ± 1.58 years, the duration of DM was on average 8.55 ± 0.65 years (with a range from the first identified to 18 years). The second group consisted of 35 people (11 women and 24 men with normal body weight (body mass index ≤25), the average age was 56.91 ± 1.95 years, the duration of DM was on average 5.73 ± 1.02 years (with a range from the first identified to 22 years). As a control, a group of 28 practically healthy individuals was examined, which was comparable to the first and second groups in terms of gender (11 women, 17 men) and age (56.05 ± 1.88 years old). Dapagliflozin was prescribed to the examined persons of the 1 st group in a daily dose of 10 mg as an antidiabetic agent as part of complex therapy. All examinations were carried out before the start of dapagliflozin treatment, as well as after 12 weeks of therapy. Results. Patients with type 2 DM and EBW showed the highest level of expression of caspase-3, TGF-β1 and an increase in arterial stiffness in elastic and muscular vessels compared to patients with type 2 DM without EBW, and especially compared to the control group. During treatment with dapagliflozin as part of complex therapy, a significant decrease in the TGF-β1 index, caspase-3 expression and a decrease in the speed of pulse wave propagation through the muscular and elastic arteries on the upper and lower extremities were recorded in patients with type 2 DM in combination with EBW and obesity. Conclusions. Dapagliflozin therapy, in addition to reliable inhibition of fibrosis processes and mechanisms of apoptosis activation in diabetes, also statistically significantly improves the arterial wall stiffness of both elastic and muscular vessels, reducing the progression of vasculopathies. In individuals with increased expression markers of fibrosis TGF-β1, significantly more rigid vessels of the elastic and muscular type are determined, which indicates a possible pathogenetic role of TGF-β1 as one of the potential prognostic biomarkers of arterial stiffness and a negative factor of cardiovascular risk in patients with type 2 DM in combination with EBW.