Soluble urokinase plasminogen activator receptor levels are elevated and associated with complications in patients with type 1 diabetes

ObjectivesSoluble urokinase plasminogen activator receptor (suPAR) is a marker of inflammation and endothelial dysfunction. We investigated the associations between suPAR and diabetes, including diabetes duration and complications, in patients with type 1 diabetes. Design, setting and subjectsFrom 2009 to 2011, 667 patients with type 1 diabetes and 51 nondiabetic control subjects were included in a cross-sectional study at Steno Diabetes Center, Gentofte, Denmark. suPAR levels were measured with an enzyme-linked immunosorbent assay. Main outcome measuresThe investigated diabetic complications were cardiovascular disease (CVD: previous myocardial infarction, revascularisation, peripheral arterial disease and stroke), autonomic dysfunction (heart rate variability during deep breathing <11 beatsmin(-1)), albuminuria [urinary albumin excretion rate (UAER) 30mg/24h] or a high degree of arterial stiffness (pulse wave velocity 10ms(-1)). Analyses were adjusted for gender, age, systolic blood pressure, estimated glomerular filtration rate, UAER, glycated haemoglobin (HbA(1c)), total cholesterol, body mass index, C-reactive protein, antihypertensive treatment and smoking. ResultsSoluble urokinase plasminogen activator receptor levels were lower in control subjects versus all patients, in control subjects versus normoalbuminuric patients (UAER <30mg/24h), in normoalbuminuric patients with short (<10 years) versus long diabetes duration and were increased with degree of albuminuria (adjusted P<0.001 for all). Furthermore, suPAR levels were higher in patients with versus without CVD (n=144; 21.3%), autonomic dysfunction (n= 369; 59.2%), albuminuria (n=357; 53.1%) and a high degree of arterial stiffness (n=298; 47.2%) (adjusted P0.024). The adjusted odds ratio (95% confidence interval) values per 1 ln unit increase in suPAR were as follows: 2.5 (1.1-5.7) for CVD: 2.7 (1.2-6.2) for autonomic dysfunction; 3.8 (1.3-10.9) for albuminuria and 2.5 (1.1-6.1) for a high degree of arterial stiffness (P0.039). ConclusionThe suPAR level is higher in patients with type 1 diabetes and is associated with diabetes duration and complications independent of other risk factors. suPAR is a potential novel risk marker for the management of diabetes.