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


METHODS
From 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.


METHODS
The 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 beats min(-1) ), albuminuria [urinary albumin excretion rate (UAER) ≥30 mg/24 h] or a high degree of arterial stiffness (pulse wave velocity ≥10 m s(-1) ). Analyses were adjusted for gender, age, systolic blood pressure, estimated glomerular filtration rate, UAER, glycated haemoglobin (HbA1c ), total cholesterol, body mass index, C-reactive protein, antihypertensive treatment and smoking.


RESULTS
Soluble urokinase plasminogen activator receptor levels were lower in control subjects versus all patients, in control subjects versus normoalbuminuric patients (UAER <30 mg/24 h), 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 P ≤ 0.024). 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 (P ≤ 0.039).


CONCLUSIONS
The 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.
Steno Diabetes Center, Gentofte, Denmark.
S
S
Theilade
Department of Medicine, Glostrup Hospital, University of Copenhagen, Copenhagen, Denmark.
S
S
Lyngbaek
Steno Diabetes Center, Gentofte, Denmark.
T W
TW
Hansen
Clinical Research Centre, Hvidovre Hospital, University of Copenhagen, Copenhagen, Denmark.
J
J
Eugen-Olsen
Department of Biochemistry, Hvidovre Hospital, University of Copenhagen, Copenhagen, Denmark.
M
M
Fenger
Steno Diabetes Center, Gentofte, Denmark.|Faculty of Health, Aarhus University, Aarhus, Denmark.|Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
P
P
Rossing
Department of Medicine, Glostrup Hospital, University of Copenhagen, Copenhagen, Denmark.|Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
J L
JL
Jeppesen
D000419:Albuminuria / Q000097:blood / Q000209:etiology; D015415:Biomarkers / Q000378:metabolism; D002097:C-Reactive Protein / Q000378:metabolism; D003430:Cross-Sectional Studies; D048909:Diabetes Complications / Q000097:blood* / Q000209:etiology; D003922:Diabetes Mellitus, Type 1 / Q000097:blood* / Q000150:complications; D003925:Diabetic Angiopathies / Q000097:blood / Q000209:etiology; D003928:Diabetic Nephropathies / Q000097:blood / Q000209:etiology; D004812:Epidemiologic Methods; D005260:Female; D006801:Humans; D007676:Kidney Failure, Chronic / Q000097:blood / Q000209:etiology; D008297:Male; D008875:Middle Aged; D055293:Receptors, Urokinase Plasminogen Activator / Q000378:metabolism*
D015415:Biomarkers; D055293:Receptors, Urokinase Plasminogen Activator; D002097:C-Reactive Protein
biomarker; diabetic complications; endothelial dysfunction; inflammation; soluble urokinase plasminogen activator receptor; type 1 diabetes