West-German Centre of Diabetes and Health, Verbund Katholischer Kliniken Düsseldorf, Düsseldorf, Germany.
PLoS One. 2013 Aug 26;8(8):e72440. doi: 10.1371/journal.pone.0072440. eCollection 2013.
The hypothesis was tested that the systemic immune milieu in recent-onset type 1 diabetes is associated with residual beta cell function and other metabolic patient characteristics.
All patients (n = 89, 40% female) of the Diabetes and Atorvastatin (DIATOR) Trial were analyzed at recruitment, i.e. prior to receiving the study medication. Inclusion criteria were insulin dependent diabetes for 2 weeks to 3 months, age range 18-39 years, and islet cell autoantibodies. Blood samples were analyzed for 14 immune mediators by standard methods. Concentrations of all mediators correlated with at least one other mediator (p<0.05, Spearman correlation) giving rise to a network. Interleukin 1 receptor antagonist (IL1-RA) held a central position and was associated with both pro- and anti-inflammatory mediators. Further central elements were the pro-inflammatory mediators CRP and IL-6, the soluble adhesion molecules sICAM-1 and E-selectin, and MCP-4 which held a central position in the chemokine network. The two Th1-associated mediators IFNγ and IP-10 remained outside the network but correlated with each other. All correlations were positive (r = 0.25-0.72), i.e., high levels of pro-inflammatory mediators were accompanied by increased levels of anti-inflammatory mediators. IL-1RA was the only mediator associated with fasting and liquid mixed meal stimulated C-peptide concentrations (r = 0.31 and 0.24, p = 0.003 and 0.025, after adjustment for age, sex, BMI). There were associations between the immune mediator network and BMI (IL-1RA, CRP, IL-6, MCP-4, MIP-1ß) but few or no associations with HbA1c, insulin dose, lipid parameters, age or sex.
In patients with recent onset type 1 diabetes, systemic acute phase proteins, cytokines, chemokines and soluble adhesion molecules form a network. Among the few central elements IL-1RA has a dominant role. IL-1RA is associated with all other groups of mediators and is the only mediator which correlates (positively) with residual beta cell function.
ClinicalTrials.gov registration number: NCT00974740.
本研究旨在测试这样一种假设，即新发 1 型糖尿病患者的全身免疫环境与胰岛β细胞功能的残留和其他代谢患者特征有关。
在接受研究药物之前，即 DIATOR 试验的所有患者（n=89，40%为女性）在招募时进行了分析。纳入标准为 2 周至 3 个月内依赖胰岛素的糖尿病、年龄在 18-39 岁之间，以及胰岛细胞自身抗体。通过标准方法分析了 14 种免疫介质的血液样本。所有介质的浓度均与至少一种其他介质相关（p<0.05，Spearman 相关性），从而形成一个网络。白细胞介素 1 受体拮抗剂（IL1-RA）处于中心位置，与促炎和抗炎介质均相关。进一步的中心要素包括促炎介质 CRP 和 IL-6、可溶性黏附分子 sICAM-1 和 E-选择素以及在趋化因子网络中处于中心位置的 MCP-4。两个 Th1 相关介质 IFNγ和 IP-10 位于网络之外，但彼此相关。所有相关性均为阳性（r=0.25-0.72），即高水平的促炎介质伴随着抗炎介质水平的升高。IL-1RA 是唯一与空腹和液体混合餐刺激 C 肽浓度相关的介质（r=0.31 和 0.24，p=0.003 和 0.025，调整年龄、性别、BMI 后）。免疫介质网络与 BMI 之间存在关联（IL-1RA、CRP、IL-6、MCP-4、MIP-1β），但与 HbA1c、胰岛素剂量、血脂参数、年龄或性别之间关联较少或没有关联。
在新发 1 型糖尿病患者中，全身急性期蛋白、细胞因子、趋化因子和可溶性黏附分子形成一个网络。在少数中心要素中，IL-1RA 占据主导地位。IL-1RA 与所有其他介质群相关，并且是唯一与之呈正相关（r=0.31 和 0.24，p=0.003 和 0.025，调整年龄、性别、BMI 后）的介质，且与残留的胰岛β细胞功能相关。
ClinicalTrials.gov 注册号：NCT00974740。
