Helmersson Johanna, Vessby Bengt, Larsson Anders, Basu Samar
Section of Geriatrics and Clinical Nutrition Research, Uppsala University, Uppsala, Sweden.
Circulation. 2004 Apr 13;109(14):1729-34. doi: 10.1161/01.CIR.0000124718.99562.91. Epub 2004 Mar 22.
Involvement of cyclooxygenase (COX)-mediated inflammation in type 2 diabetes has not been studied, and the association between cytokine-mediated inflammation and diabetes is not fully clarified.
15-Keto-dihydro-prostaglandin F2alpha (a metabolite of prostaglandin F2alpha and an indicator of COX-mediated inflammation), high-sensitivity C-reactive protein (CRP), serum amyloid protein A (SAA), 8-iso-PGF2alpha (a nonenzymatic, free radical product of arachidonic acid and an indicator of oxidative stress), and alpha-tocopherol were measured in a population-based sample of 77-year-old men (n=765), in which 112 men had type 2 diabetes. The inflammatory indicators were increased in men with diabetes (urinary 15-keto-dihydro-PGF2alpha, P<0.001, CRP and SAA, P<0.05). However, when adjusted for body mass index, waist circumference, or fasting insulin, no association was found between diabetes and CRP or SAA. The oxidative stress indicator 8-iso-PGF2alpha in urine was increased (P<0.01) in men with diabetes. Patients who were newly diagnosed with diabetes (<7 years since diagnosis) had increased urinary 15-keto-dihydro-PGF2alpha and decreased alpha-tocopherol, but 8-iso-PGF2alpha was unaltered.
This is the first study to show that type 2 diabetes in elderly men is related to COX-mediated inflammation, reflected by enhanced prostaglandin formation. The high levels of cytokine-mediated acute-phase proteins observed in men with diabetes appear to be related to obesity and increased fasting insulin. The results further suggest that the appearance of chronic inflammation is an early process in the pathogenesis of diabetes, whereas oxidative injury may be a later process, possibly related to inflammation.
环氧化酶（COX）介导的炎症在2型糖尿病中的作用尚未得到研究，细胞因子介导的炎症与糖尿病之间的关联也未完全阐明。
在一个基于人群的77岁男性样本（n = 765）中，测量了15-酮二氢前列腺素F2α（前列腺素F2α的代谢产物，COX介导炎症的指标）、高敏C反应蛋白（CRP）、血清淀粉样蛋白A（SAA）、8-异前列腺素F2α（花生四烯酸的非酶自由基产物，氧化应激指标）和α-生育酚，其中112名男性患有2型糖尿病。糖尿病男性的炎症指标升高（尿15-酮二氢前列腺素F2α，P < 0.001；CRP和SAA，P < 0.05）。然而，在调整体重指数、腰围或空腹胰岛素后，未发现糖尿病与CRP或SAA之间存在关联。糖尿病男性尿中的氧化应激指标8-异前列腺素F2α升高（P < 0.01）。新诊断为糖尿病（诊断后<7年）的患者尿15-酮二氢前列腺素F2α升高，α-生育酚降低，但8-异前列腺素F2α未改变。
这是第一项表明老年男性2型糖尿病与COX介导的炎症相关的研究，前列腺素生成增加反映了这一点。糖尿病男性中观察到的高水平细胞因子介导的急性期蛋白似乎与肥胖和空腹胰岛素升高有关。结果进一步表明，慢性炎症的出现是糖尿病发病机制中的早期过程，而氧化损伤可能是后期过程，可能与炎症有关。
