Angiotensin II and transforming growth factor β affect cardiovascular and renal disease in patients with type 2 diabetes mellitus: benefits of dpp-4 inhibitors treatment

Abstract

BACKGROUND: Diabetes mellitus type 2 (T2DM) is associated with impaired glucose metabolism and peripheral insulin resistance, which is accompanied by an high risk of cardiovascular disease (CVD) and nephropathy. Metabolic syndrome and T2DM are accompanied by renin-angiotensin system (RAS) activation, which is also associated with increased risk of CVD and kidney damage. Obesity lead to a wide range of pathophysiological changes, that stimulate cardiac fibrosis, and various fibrosis processes initiation, including activation of transforming growth factor (TGF-).
 AIMS: To determine activity of angiotensin II (Ang II) and TGF- in patients with obesity and T2DM and their association with heart and kidney damage.
 MATERIALS AND METHODS: Ang II and TGF- were identified in the peripheral blood of 66 obese patients aged 48-65 years. The first group included 21 patients with coronary heart disease (CHD) and T2DM; The second group included 22 patients with T2DM and excluded CHD; The third group 20 patients with normal glucose metabolism and excluded CHD.
 RESULTS: The values of TGF- in the 1st group (patients with CHD) were statistically lower than in the group of metabolically healthy obesity (p=0.021). Patients who received DPP-4 inhibitors had a lower Ang II level compared to patients with other hypoglycemic therapy (p=0.005). TGF- positively correlated with glomerular filtration rate (eGFR) in all patients (r=-0.414, p=0.006). TGF- negatively correlated with the degree of internal carotid artery stenosis in patients of the 2nd group (r=-0.42, p=0.09) and LDL-cholesterol in all patients (r=-0.426, p=0.038).
 CONCLUSIONS: TGF- negatively correlated with the factors that contribute to CVD progression. TGF- correlated with pathological angiogenesis and changes in normal cardiac geometry in obesity, T2DM and CHD. DPP-4 inhibitors can improve the cardiovascular prognosis in this group of patients by affecting Ang II level. Low levels of TGF- were associated with higher cardiovascular risk and were commonly found in patients with more severe nephropathy.