Davì Giovanni, Chiarelli Francesco, Santilli Francesca, Pomilio Mariapina, Vigneri Sergio, Falco Angela, Basili Stefania, Ciabattoni Giovanni, Patrono Carlo
Center of Excellence on Aging and Department of Medicine, University of Chieti G. D'Annunzio Schools of Medicine and Pharmacy, Chieti, Italy.
Circulation. 2003 Jul 1;107(25):3199-203. doi: 10.1161/01.CIR.0000074205.17807.D0. Epub 2003 Jun 16.
To investigate early events possibly related to the development of diabetic angiopathy, we examined whether 8-iso-prostaglandin F2alpha (8-iso-PGF2alpha) formation, a marker of in vivo oxidant stress, is altered in different stages of type 1 diabetes (T1DM) and whether it correlates with the rate of thromboxane (TX) A2 biosynthesis, a marker of in vivo platelet activation. We also investigated the relationship between inflammatory markers and F2-isoprostane formation in this setting.
A cross-sectional study was performed in 23 insulin-treated patients aged <18 years with new-onset T1DM (<or=6 weeks, group A), matched for age and gender with 23 patients with stable disease (>1 year, group B). Urinary 8-iso-PGF2alpha and 11-dehydro-TXB2 were measured in all patients and in age- and gender-matched controls. Circulating interleukin-6 (IL-6), tumor necrosis factor-alpha, and C-reactive protein were also determined as markers of the inflammatory response. Fifteen of the 23 children in group A were reexamined after 12 months. Compared with either controls or group B, diabetic children in group A showed significantly higher levels of 8-iso-PGF2alpha, 11-dehydro-TXB2, IL-6, tumor necrosis factor-alpha, and C-reactive protein. Statistically significant correlations between IL-6 and both 8-iso-PGF2alpha (r=0.63, P<0.001) and 11-dehydro-TXB2 (r=0.51, P<0.01) were observed. The 15 patients reexamined after 1 year showed a significant reduction in lipid peroxidation and platelet activation (P<0.02 and P<0.001, respectively), consistent with reduced levels of IL-6 and tumor necrosis factor-alpha.
These results demonstrate that enhanced lipid peroxidation and platelet activation represent early events in T1DM that are possibly related to an acute inflammatory response. These noninvasive indexes may help in further examining T1DM pathophysiology and monitoring pharmacological interventions to interfere with disease development and progression.
为了研究可能与糖尿病血管病变发展相关的早期事件，我们检测了1型糖尿病（T1DM）不同阶段体内氧化应激标志物8-异前列腺素F2α（8-iso-PGF2α）的生成是否发生改变，以及它是否与体内血小板活化标志物血栓素（TX）A2的生物合成速率相关。我们还研究了在这种情况下炎症标志物与F2-异前列腺素生成之间的关系。
对23例年龄小于18岁、新诊断为T1DM（≤6周，A组）且接受胰岛素治疗的患者进行了横断面研究，按照年龄和性别与23例病情稳定（>1年，B组）的患者进行匹配。检测了所有患者以及年龄和性别匹配的对照组的尿8-iso-PGF2α和11-脱氢-TXB2。还测定了循环白细胞介素-6（IL-6）、肿瘤坏死因子-α和C反应蛋白作为炎症反应的标志物。A组23名儿童中有15名在12个月后进行了复查。与对照组或B组相比，A组糖尿病儿童的8-iso-PGF2α、11-脱氢-TXB2、IL-6、肿瘤坏死因子-α和C反应蛋白水平显著更高。观察到IL-6与8-iso-PGF2α（r=0.63，P<0.001）和11-脱氢-TXB2（r=0.51，P<0.01）之间存在统计学显著相关性。1年后复查的15例患者脂质过氧化和血小板活化显著降低（分别为P<0.02和P<0.001），与IL-6和肿瘤坏死因子-α水平降低一致。
这些结果表明，脂质过氧化增强和血小板活化是T1DM中的早期事件，可能与急性炎症反应有关。这些非侵入性指标可能有助于进一步研究T1DM的病理生理学，并监测旨在干扰疾病发展和进程的药物干预措施。
