Increased plasma urotensin-II levels are associated with diabetic retinopathy and carotid atherosclerosis in Type 2 diabetes

Abstract

Human U-II (urotensin-II), the most potent vasoconstrictor peptide identified to date, is associated with cardiovascular disease. A single nucleotide polymorphism (S89N) in the gene encoding U-II (UTS2) is associated with the onset of Type 2 diabetes and insulin resistance in the Japanese population. In the present study, we have demonstrated a relationship between plasma U-II levels and the progression of diabetic retinopathy and vascular complications in patients with Type 2 diabetes. Eye fundus, IMT (intima-media thickness) and plaque score in the carotid artery, BP (blood pressure), FPG (fasting plasma glucose), HbA(1c) (glycated haemoglobin), U-II, angiogenesis-stimulating factors, such as VEGF (vascular endothelial growth factor) and heregulin-beta(1), and lipid profiles were determined in 64 patients with Type 2 diabetes and 24 non-diabetic controls. FPG, HbA(1c) and VEGF levels were significantly higher in patients with Type 2 diabetes than in non-diabetic controls. Diabetes duration, insufficient glycaemic and BP control, plasma U-II levels, IMT, plaque score and nephropathy grade increased significantly across the subjects as follows: non-diabetic controls, patients with Type 2 diabetes without retinopathy (group N), patients with Type 2 diabetes with simple (background) retinopathy (group A) and patients with Type 2 diabetes with pre-proliferative and proliferative retinopathy (group B). The prevalence of obesity and smoking, age, low-density lipoprotein, triacylglycerols (triglycerides) and heregulin-beta(1) were not significantly different among the four groups. In all subjects, U-II levels were significantly positively correlated with IMT, FPG, and systolic and diastolic BP. Multiple logistic regression analysis revealed that, of the above parameters, U-II levels alone had a significantly independent association with diabetic retinopathy. In conclusion, the results of the present study provide the first evidence that increased plasma U-II levels may be associated with the progression of diabetic retinopathy and carotid atherosclerosis in patients with Type 2 diabetes.

Urotensin II receptor antagonism confers vasoprotective effects in diabetes associated atherosclerosis: studies in humans and in a mouse model of diabetes

“…UII is thought to play a role in atherosclerosis and may be particularly relevant in the diabetic setting, where plasma UII levels are elevated [21][22][23]. This is the first study to specifically investigate the role of UII and the UT in experimental and clinical diabetes-associated atherosclerosis.…”

International Union of Basic and Clinical Pharmacology. XCII. Urotensin II, Urotensin II–Related Peptide, and Their Receptor: From Structure to Function

“…Elevated UII levels have been detected in the plasma of diabetic patients (Totsune et al, , 2004Krum and Gilbert, 2003;Suguro et al, 2008), particularly in individuals presenting with metabolic syndrome (Ong et al, 2008;Oguri et al, 2009;Gruson et al, 2010b). In addition, overexpression of UII and UT has been reported in the kidney of diabetic patients (Langham et al, 2004).…”

Role of urotensin II in health and disease

“…In heart failure, UII plasma concentrations are not only increased but also correlate with Big endothelin-1 (Big-ET-1) and brain natriuretic peptide levels as well as with New York Heart Association functional class (43,93) and negatively correlate with left ventricular ejection fraction (43). Recent evidence suggests that UII is also a useful biomarker for diabetic retinopathy and carotid atherosclerosis in type 2 diabetes (119) and in rheumatic valve disease (93). Paradoxically, in some diseases, high plasma UII levels may actually be a marker for a decreased risk of fatal events (83).…”