Increased urinary orosomucoid excretion: a proposed marker for inflammation and endothelial dysfunction in patients with type 2 diabetes.
OBJECTIVE
In a previous study, urinary orosomucoid excretion rate (UOER) independently predicted cardiovascular mortality in patients with type 2 diabetes. The aim of the present study was to determine whether increased UOER is associated with cardiovascular risk factors such as inflammation, impaired left ventricular function and endothelial dysfunction in patients with type 2 diabetes.


METHODS
We performed a cross-sectional study of 41 patients with type 2 diabetes (17 patients with normal UOER and 24 with increased UOER) with no history of cardiovascular disease and 21 healthy controls. Urinary orosomucoid was measured using a particle-enhanced immunoturbidimetric assay. Plasma interleukin-6 (IL-6), tissue plasminogen activator (tPA) and soluble intercellular adhesion molecule-1 (sICAM) were measured using ELISA. Endothelial function measured as vasodilatory capacity of the brachial artery and echocardiography were done in all participants.


RESULTS
Patients with diabetes and increased UOER had subclinically increased serum orosomucoid (p<0.001), C-reactive protein (CRP) (p<0.001), IL-6 (p<0.001), tPA (p<0.003) and sICAM (p<0.003) compared with healthy controls. In patients with type 2 diabetes, UOER was independently associated with increasing values of IL-6 (1.43 (1.06-1.93)) and tPA (1.82 (1.20-2.77)). Measurements by echocardiography showed no signs of cardiac dysfunction.


CONCLUSIONS
Asymptomatic patients with type 2 diabetes and increased UOER displayed signs of chronic low-grade inflammation and endothelial dysfunction. UOER was independently related to markers of proinflammation and endothelial dysfunction in patients with type 2 diabetes. The previously shown relation between increased UOER and cardiovascular mortality is proposed to be caused by chronic low-grade inflammation and early endothelial dysfunction.
Christiansen
M S
MS
Department of Clinical Biochemistry, Amager Hospital, Copenhagen, Denmark. skovdal@dadlnet.dk
Iversen
K
K
Larsen
C T
CT
Goetze
J P
JP
Hommel
E
E
Mølvig
J
J
Pedersen
B K
BK
Magid
E
E
Feldt-Rasmussen
B
B
D000328:Adult; D000368:Aged; D002097:C-Reactive Protein / Q000378:metabolism; D016022:Case-Control Studies; D003430:Cross-Sectional Studies; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000503:physiopathology / Q000652:urine*; D004730:Endothelium, Vascular / Q000503:physiopathology*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D007249:Inflammation / Q000652:urine*; D018799:Intercellular Adhesion Molecule-1 / Q000097:blood; D015850:Interleukin-6 / Q000097:blood; D008297:Male; D008875:Middle Aged; D009961:Orosomucoid / Q000652:urine*; D010959:Tissue Plasminogen Activator / Q000097:blood
D015850:Interleukin-6; D009961:Orosomucoid; D018799:Intercellular Adhesion Molecule-1; D002097:C-Reactive Protein; D010959:Tissue Plasminogen Activator