Cifarelli Vincenza, Libman Ingrid M, Deluca Angela, Becker Dorothy, Trucco Massimo, Luppi Patrizia
Division of Immunogenetics, Department of Pediatrics, Children´s Hospital of Pittsburgh, University of Pittsburgh, School of Medicine, Pittsburgh, PA 15213, USA.
Rev Diabet Stud. 2007 Summer;4(2):112-7. doi: 10.1900/RDS.2007.4.112. Epub 2007 Aug 10.
Compelling evidence implicates inflammation in the pathogenesis of type 1 diabetes mellitus (T1DM) and associated vascular complications. Obesity is also characterized by low-grade systemic inflammation. In this study, we characterized the inflammatory response in diabetes by analyzing the expression of a panel of activation markers on the surface of peripheral blood monocytes in recently-diagnosed T1DM patients. The potential effects of glycemic control and body mass index (BMI) on monocyte phenotype were also investigated.
Using flow cytometry, we analyzed the expression of CD11b, CD49d, CD54, CD62L and CD64 antigens on monocytes in a cohort of 51 T1DM patients (</= 2 months after diagnosis). To test whether phenotype change in monocytes was associated with abnormal cellular function, we studied the adhesive capacity of monocytes to human umbilical vein endothelial cells (HUVEC).
We found that circulating monocytes from T1DM patients tested at the clinical onset of the disease (i.e. within 1 week of diagnosis) had higher CD11b expression compared to patients analyzed 2 months after diagnosis (p = 0.02). The highest CD11b levels were detected in patients with HbA1c < 8% (p = 0.04 vs. patients with HbA1c < 8%). In T1DM children analyzed 2 months after diagnosis, we found that those who were overweight (BMI >/= 85th percentile) had higher levels of monocyte activation than those who were not (BMI </= 85th percentile) (p = 0.03). CD11b and HbA1c were significantly correlated (correlation coefficient 0.329, p = 0.02). Finally, monocytes from T1DM patients showed higher adhesion to HUVEC compared to controls.
Circulating immune cells from T1DM patients display many aspects of a proinflammatory state, as indicated by primed or activated monocytes. Obesity is an important factor in monocyte activation during diabetes.
有力证据表明炎症参与1型糖尿病（T1DM）及其相关血管并发症的发病机制。肥胖也具有低度全身性炎症的特征。在本研究中，我们通过分析新诊断的T1DM患者外周血单核细胞表面一组活化标志物的表达，来描述糖尿病中的炎症反应。还研究了血糖控制和体重指数（BMI）对单核细胞表型的潜在影响。
我们使用流式细胞术分析了51例T1DM患者（诊断后≤2个月）队列中单核细胞上CD11b、CD49d、CD54、CD62L和CD64抗原的表达。为了测试单核细胞的表型变化是否与细胞功能异常相关，我们研究了单核细胞与人脐静脉内皮细胞（HUVEC）的黏附能力。
我们发现，在疾病临床发病时（即诊断后1周内）检测的T1DM患者的循环单核细胞与诊断后2个月分析的患者相比，CD11b表达更高（p = 0.02）。在糖化血红蛋白（HbA1c）<8%的患者中检测到最高的CD11b水平（与HbA1c≥8%的患者相比，p = 0.04）。在诊断后2个月分析的T1DM儿童中，我们发现超重（BMI≥第85百分位数）的儿童比未超重（BMI≤第85百分位数）的儿童单核细胞活化水平更高（p = 0.03）。CD11b与HbA1c显著相关（相关系数0.329，p = 0.02）。最后，与对照组相比，T1DM患者的单核细胞对HUVEC的黏附性更高。
如经致敏或活化的单核细胞所示，T1DM患者的循环免疫细胞表现出促炎状态的多个方面。肥胖是糖尿病期间单核细胞活化的一个重要因素。
