Urinary leukotriene E4 excretion is increased in type 1 diabetic patients: a quantification by liquid chromatography-tandem mass spectrometry.
OBJECTIVE
Diabetes mellitus is associated with inflammatory state and increased cardiovascular mortality. Leukotrienes are arachidonic acid metabolites derived from the 5-lipoxygenase pathway that possess vasoactive, chemotactic and proinflammatory properties. The aim of this study was to evaluate (1) the urinary excretion of leukotriene E4 (LTE4) in type 1 diabetic subjects and healthy volunteers and (2) the influence of glycemic control attested by HbA(1C) on LTE4 excretion.


RESULTS
Urinary excretion of LTE(4), measured by liquid chromatography-tandem mass spectrometry, was significantly (P=0.033) increased in diabetic patients (median [10th-90th percentiles]: 42.1 pg/mg creatinine [16.7-71.4], n=34), compared to healthy subjects (25.5 pg/mg creatinine [13.9-54.1], n=28). Subgroup analysis indicated a trend towards increased LTE4 excretion in patients with poor glycemic control [(HbA(1C)> or =9% or plasma glucose >18 mmol/L): 43.3 pg/mg creatinine [21.6-70.5], n=14], whereas no difference was observed between patients with good metabolic control [(HbA(1C)< or =7.5%): 36.4 pg/mg creatinine [15.8-83.4], n=20] and healthy subjects.


CONCLUSIONS
This study suggested that increased LTE4 excretion in type 1 diabetic state might reflect systemic activation of the 5-lipoxygenase pathway. It could be a determinant of underlying inflammatory state and vascular disease.
Hardy
Gaëlle
G
Laboratory of Pharmacology, Laboratory HP2 INSERM ESPRI EA3745, University of Medicine, F-38706 La Tronche Cedex, France.
Boizel
Robert
R
Bessard
Janine
J
Cracowski
Jean-Luc
JL
Bessard
Germain
G
Halimi
Serge
S
Stanke-Labesque
Françoise
F
D000328:Adult; D001094:Arachidonate 5-Lipoxygenase / Q000378:metabolism; D001786:Blood Glucose / Q000032:analysis; D016022:Case-Control Studies; D002853:Chromatography, Liquid / Q000379:methods*; D003922:Diabetes Mellitus, Type 1 / Q000652:urine*; D004789:Enzyme Activation; D005260:Female; D006442:Glycated Hemoglobin / Q000032:analysis; D006801:Humans; D017999:Leukotriene E4 / Q000652:urine*; D008297:Male; D013058:Mass Spectrometry / Q000379:methods*; D008875:Middle Aged
D001094:Arachidonate 5-Lipoxygenase; D001786:Blood Glucose; D006442:Glycated Hemoglobin; D017999:Leukotriene E4