Hardy Gaëlle, Boizel Robert, Bessard Janine, Cracowski Jean-Luc, Bessard Germain, Halimi Serge, Stanke-Labesque Françoise
Laboratory of Pharmacology, Laboratory HP2 INSERM ESPRI EA3745, University of Medicine, F-38706 La Tronche Cedex, France.
Prostaglandins Other Lipid Mediat. 2005 Dec;78(1-4):291-9. doi: 10.1016/j.prostaglandins.2005.10.001. Epub 2005 Nov 2.
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.
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.
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.
糖尿病与炎症状态及心血管死亡率增加相关。白三烯是花生四烯酸经5-脂氧合酶途径代谢产生的产物,具有血管活性、趋化性和促炎特性。本研究的目的是评估:(1)1型糖尿病患者和健康志愿者中白三烯E4(LTE4)的尿排泄情况;(2)糖化血红蛋白(HbA1C)所证实的血糖控制对LTE4排泄的影响。
采用液相色谱-串联质谱法测定LTE4的尿排泄量,结果显示糖尿病患者(中位数[第10-90百分位数]:42.1 pg/mg肌酐[16.7-71.4],n=34)的LTE4排泄量显著增加(P=0.033),而健康受试者(25.5 pg/mg肌酐[13.9-54.1],n=28)的排泄量较低。亚组分析表明,血糖控制不佳的患者(HbA1C≥9%或血浆葡萄糖>18 mmol/L)LTE4排泄量有增加趋势:43.3 pg/mg肌酐[21.6-70.5],n=14;而代谢控制良好的患者(HbA1C≤7.5%):36.4 pg/mg肌酐[15.8-83.4],n=20与健康受试者之间无差异。
本研究提示,1型糖尿病状态下LTE4排泄增加可能反映了5-脂氧合酶途径的全身激活。它可能是潜在炎症状态和血管疾病的一个决定因素。