Soluble urokinase plasminogen activator receptor levels are elevated and associated with complications in patients with type 1 diabetes
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OBJECTIVES: 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.
DESIGN, SETTING AND SUBJECTS: 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.
MAIN OUTCOME MEASURES: 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).
CONCLUSION: 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.
Original language | English |
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Journal | Journal of Internal Medicine |
Volume | 277 |
Issue number | 3 |
Pages (from-to) | 362-371 |
Number of pages | 10 |
ISSN | 0954-6820 |
DOIs | |
Publication status | Published - Mar 2015 |
- Albuminuria, Biomarkers, C-Reactive Protein, Cross-Sectional Studies, Diabetes Complications, Diabetes Mellitus, Type 1, Diabetic Angiopathies, Diabetic Nephropathies, Epidemiologic Methods, Female, Humans, Kidney Failure, Chronic, Male, Middle Aged, Receptors, Urokinase Plasminogen Activator
Research areas
ID: 152244487