Soluble Urokinase Plasminogen Activator Receptor Levels Are Elevated and Associated With Complications in Patients With Type 1 Diabetes

J Intern Med. 2015 Mar;277(3):362-371. doi: 10.1111/joim.12269. Epub 2014 Jun 23.

Abstract

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.

Keywords: biomarker; diabetic complications; endothelial dysfunction; inflammation; soluble urokinase plasminogen activator receptor; type 1 diabetes.

MeSH terms

  • Albuminuria / blood
  • Albuminuria / etiology
  • Biomarkers / metabolism
  • C-Reactive Protein / metabolism
  • Cross-Sectional Studies
  • Diabetes Complications / blood*
  • Diabetes Complications / etiology
  • Diabetes Mellitus, Type 1 / blood*
  • Diabetes Mellitus, Type 1 / complications
  • Diabetic Angiopathies / blood
  • Diabetic Angiopathies / etiology
  • Diabetic Nephropathies / blood
  • Diabetic Nephropathies / etiology
  • Epidemiologic Methods
  • Female
  • Humans
  • Kidney Failure, Chronic / blood
  • Kidney Failure, Chronic / etiology
  • Male
  • Middle Aged
  • Receptors, Urokinase Plasminogen Activator / metabolism*

Substances

  • Biomarkers
  • Receptors, Urokinase Plasminogen Activator
  • C-Reactive Protein