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

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 β (TGF-β). AIMS: To determine activity of angiotensin II (Ang II) and TGF-β in patients with obesity and T2DM and their association with heart and kidney damage. MATERIALS AND METHODS: Ang II and TGF-β 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-β 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-β positively correlated with glomerular filtration rate (eGFR) in all patients (r=-0.414, p=0.006). TGF-β 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-β negatively correlated with the factors that contribute to CVD progression. TGF-β 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-β were associated with higher cardiovascular risk and were commonly found in patients with more severe nephropathy

Primary hyperparathyroidism in combination with metabolic syndrome and sleep apnea

This paper presents a case of primary hyperparathyroidism with a broad spectrum of metabolic disturbances and concomitant sleep apnea syndrome. As shown a timely surgical treatment helps to improve the mineral parameters and alleviate the risk of possible cardiovascular complications in future. The article is the RePrint from the original publication in Obesity and Metabolism (2014) 11(3); pp. 51-55. doi: 10.14341/omet2014351-5

TGF-β and FRF-21: association with coronary artery disease in patients with type 2 diabetes and obesity

Backgraund: Obesity and type 2 diabetes mellitus (T2DM) are associated with with an increased risk of cardiovascular disease (CVD) and coronary artery disease (CAD), in particular. Obesity lead to several fibrotic processes, including activation of transforming growth factor β (TGF-β). Recent data indicate the involvement of Fibroblast growth factor 21 (FGF-21) as an important metabolic regulator, and even biomarker of metabolic changes in obesity and T2DM. Impact of metabolic dysregulation that accompany obesity and T2DM in CAD development remain a great challenge. Aims: To study TGF-β and FGF-21 level in patients with obesity and T2DM. Materials and methods: TGF-β and FGF-21 were identified in peripheral blood samples of 66 patients with obesity, aged 48-65 years. 1st group included 21 patients with CHD and T2DM; 2nd group (22 patients)- with T2DM and excluded CHD; 3rd group (20 patients) with normal glucose metabolism and excluded CHD. Results: TGF-β was lower in patients with CHD (group 1) than in the group of "metabolically healthy" obesity (p=0.022). TGF-β in patients with T2DM negatively correlated with LDL cholesterol (r=-0.426, p=0.038) the degree of internal carotid artery stenosis (r=-0.426, p=0.024). Patients with verified CHD had a negative correlation with the processes of heart muscle remodeling (thickness of the left ventricular posterior wall (r=- 0.386, p=0.029) interventricular septum (r=-0.335, p=0.031). All patients with obesity had significantly increased level of FGF-21 compared with the control group (p=0.031) FGF-21 positively correlated with BMI (r=0.473, p=0.033) Conclusions: TGF-β has negative correlations with the factors that can influence prognosis and the severity of the CVD/. There were found correlations of FGF-21, TGF-β with pathological angiogenesis and changes in normal cardiac geometry in obesity, T2DM and CAD

Profile of microRNAs associated with coronary heart disease in patients with type 2 diabetes

Introduction. Cardiovascular disease (CVD) remain the leading cause of death in industrialized countries. Patients with coronary heart disease (CHD) in combination with diabetes mellitus type 2 (T2DM) are characterized by more severe CHD and poor prognosis. Resent data indicate microRNAs (miRNAs) as important participants in the pathogenesis of various pathological conditions, including obesity, T2DM and CVD.The aim of this study was to determine expression of miRNAs associated with the development of CHD, and transforming growth factor beta (TGF-β) in a patients with T2DM and obesity Materials and methods. 42 patients with 1-2 degrees obesity and diagnosed T2DM were divided into 2 groups. The first group with CHD, the second group - without CHD. 9 miRNAs were evaluated: miRNA-1, miRNA-21, miRNA-26a, m miRNA-27, miRNA-33a, miRNA-33b, miRNA-133a, miRNA-133b, miRNA-208.Results and discussion. Significant differences were found in expression of miRNA-21, miRNA-26a, miRNA27a. An increased expression of miRNA-21, miRNA-27a was found in patients CHD while the expression of miRNA-26a was reduced in comparison with the group without CHD.Conclusion. The results of this study may be an initial step for the detection of molecular basis in CHD pathogenesis in these patients by quantifying miRNA expression. Introduction. Cardiovascular disease (CVD) remain the leading cause of death in industrialized countries. Patients with coronary heartdisease (CHD) in combination with diabetes mellitus type 2 (T2DM) are characterized by more severe CHD and poor prognosis. Resent data indicate microRNAs (miRNAs) as important participants in the pathogenesis of various pathological conditions, including obesity, T2DM and CVD.The aim of this study was to determine expression of miRNAs associated with the development of CHD, and transforming growth factor beta (TGF-β) in a patients with T2DM and obesity Materials and methods. 42 patients with 1-2 degrees obesity and diagnosed T2DM were divided into 2 groups. The first group with CHD, the second group - without CHD. 9 miRNAs were evaluated: miRNA-1, miRNA-21, miRNA-26a, m miRNA-27, miRNA-33a, miRNA-33b, miRNA-133a, miRNA-133b, miRNA-208.Results and discussion. Significant differences were found in expression of miRNA-21, miRNA-26a, miRNA27a. An increased expression of miRNA-21, miRNA-27a was found in patients CHD while the expression of miRNA-26a was reduced in comparison with the group without CHD.Conclusion. The results of this study may be an initial step for the detection of molecular basis in CHD pathogenesis in these patients by quantifying miRNA expression