4.1 Article

Increased urinary orosomucoid excretion: a proposed marker for inflammation and endothelial dysfunction in patients with type 2 diabetes

出版社

TAYLOR & FRANCIS LTD
DOI: 10.1080/00365510802531100

关键词

Albuminuria; inflammation; intercellular adhesion molecule-1; orosomucoid; tissue plasminogen activator; vasodilation; ventricular function (left)

资金

  1. Danish Kidney Foundation
  2. Novo Nordisk Foundation
  3. Johan and Lise Boserup Foundation
  4. Bernhard and Marie Klein Foundation
  5. Diabetes Research and the Foundation of the Copenhagen Hospital Corporation.

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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. Material and 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 (p0.001), C-reactive protein (CRP) (p0.001), IL-6 (p0.001), tPA (p0.003) and sICAM (p0.003) 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.

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