leukotriene-e4 and Diabetes-Mellitus--Type-2

Topics: Adult; Arachidonate 5-Lipoxygenase; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Female; Humans; Hypoglycemic Agents; Insulin; Leukotriene E4; Male; Middle Aged; Oxidative Stress; Thromboxane B2

Topics: Adult; Asthma; Child; Diabetes Mellitus, Type 2; Humans; Inflammation; Leukotriene E4; Prostaglandin D2

The aim of the present study was to investigate the effect of genetic polymorphisms in candidate genes within the leukotriene (LT) pathway on platelet reactivity and the concentration of selected LTs in diabetic patients treated with acetylsalicylic acid (ASA). The study cohort consisted of 287 Caucasians with type 2 diabetes who had received treatment with ASA tablets (75 mg/day) for at least three months. Platelet reactivity analyses were performed using VerifyNow aspirin and PFA‑100 assays. The measured LTs included leukotriene B4 (LTB4) and leukotriene E4 (LTE4). Genotyping for the selected 25 single nucleotide polymorphisms (SNPs) within six genes of the LT pathway was performed using a Sequenom iPLEX platform. No statistically significant association was observed between the investigated SNP genotypes, platelet reactivity and measured LTs in the patient cohort. The results of our study suggest that certain polymorphisms of the LT pathway are not associated with altered platelet reactivity and the measured LTs in diabetic patients treated with ASA.

Topics: 5-Lipoxygenase-Activating Proteins; Aged; Alleles; Arachidonate 12-Lipoxygenase; Arachidonate 15-Lipoxygenase; Arachidonate 5-Lipoxygenase; Aspirin; Blood Platelets; Cohort Studies; Diabetes Mellitus, Type 2; Epoxide Hydrolases; Female; Gene Frequency; Genotype; Glutathione Transferase; Humans; Leukotriene B4; Leukotriene E4; Male; Middle Aged; Polymorphism, Single Nucleotide

Leukotrienes are inflammatory and vasoactive mediators implicated in endothelium-dependent relaxations and atherosclerosis. Urinary leukotriene E4 (U-LTE4) is a validated disease marker of asthma and increases also in diabetes and acute coronary syndromes. The aim of the present study was to evaluate the association of U-LTE4 and CRP with endothelial function. Urine samples were obtained from 30 subjects (80% males; median age 65) with type 2 diabetes of at least two years duration and a median glomerular filtration rate (eGFR) of 71 (14-129) mL/min. Reactive hyperemia index (RHI) was used as a measure of microvascular endothelial function, whereas macrovascular endothelial function was determined be means of flow-mediated dilatation of the brachial artery (FMD). Decreased renal function was associated with lower concentrations of U-LTE4. In addition, U-LTE4 was correlated with serum creatinine (R = -0.572; P = 0.001) and eGFR (R = 0.517; P = 0.0036). A stepwise multiple linear regression analysis identified eGFR as an independent predictor of U-LTE4 concentrations. In conclusion, the present results did not establish an association of U-LTE4 with endothelial dysfunction. However, eGFR was an independent predictor of U-LTE4, but not CRP, in this cohort, suggesting that GFR should be considered in biomarker studies of U-LTE4.

Topics: Aged; Biomarkers; Brachial Artery; C-Reactive Protein; Case-Control Studies; Creatinine; Diabetes Mellitus, Type 2; Diabetic Nephropathies; Endothelium, Vascular; Female; Glomerular Filtration Rate; Humans; Kidney; Leukotriene E4; Male; Middle Aged; Vasodilation