Steno Diabetes Center Copenhagen, Gentofte, Denmark.
Pediatrics Department E, Herlev Hospital, Herlev, Denmark.
BMC Pediatr. 2020 Sep 23;20(1):446. doi: 10.1186/s12887-020-02339-8.
Type 1 diabetes (T1D) is caused by immune-mediated destruction of the β-cells. After initiation of insulin therapy many patients experience a period of improved residual β-cell function leading to partial disease remission. Cytokines are important immune-modulatory molecules and contribute to β-cell damage in T1D. The patterns of systemic circulating cytokines during T1D remission are not clear but may constitute biomarkers of disease status and progression. In this study, we investigated if the plasma levels of various pro- and anti-inflammatory cytokines around time of diagnosis were predictors of remission and residual β-cell function in children with T1D followed for one year after disease onset.
In a cohort of 63 newly diagnosed children (33% females) with T1D with a mean age of 11.3 years (3.3-17.7), ten cytokines were measured of which eight were detectable in plasma samples by Mesoscale Discovery multiplex technology at study start and after 6 and 12 months. Linear regression models were used to evaluate association of cytokines with stimulated C-peptide.
Systemic levels of tumor necrosis factor (TNF)-α, interleukin (IL)-2 and IL-6 inversely correlated with stimulated C-peptide levels over the entire study (P < 0.05). The concentrations of TNFα and IL-10 at study start predicted stimulated C-peptide level at 6 months (P = 0.011 and P = 0.043, respectively, adjusted for sex, age, HbA1c and stage of puberty).
In recent-onset T1D, systemic cytokine levels, and in particular that of TNFα, correlate with residual β-cell function and may serve as prognostic biomarkers of disease remission and progression to optimize treatment strategies.
The study was performed according to the criteria of the Helsinki II Declaration and was approved by the Danish Capital Region Ethics Committee on Biomedical Research Ethics (journal number H-3-2014-052). The parents of all participants gave written consent.
1 型糖尿病（T1D）是由β细胞的免疫介导破坏引起的。在开始胰岛素治疗后，许多患者经历了一段改善的残余β细胞功能的时期，导致部分疾病缓解。细胞因子是重要的免疫调节分子，有助于 T1D 中的β细胞损伤。T1D 缓解期间系统循环细胞因子的模式尚不清楚，但可能构成疾病状态和进展的生物标志物。在这项研究中，我们研究了在疾病发病后一年随访的 T1D 儿童中，诊断时各种促炎和抗炎细胞因子的血浆水平是否可预测缓解和残余β细胞功能。
在 63 名新诊断为 T1D 的儿童（33%为女性）中，有 33%为女性，平均年龄为 11.3 岁（3.3-17.7 岁），在研究开始时和 6 个月和 12 个月时，使用 Mesoscale Discovery 多重技术检测了十种细胞因子，其中八种可在血浆样本中检测到。线性回归模型用于评估细胞因子与刺激 C 肽之间的关联。
肿瘤坏死因子（TNF）-α、白细胞介素（IL）-2 和 IL-6 的系统水平与整个研究过程中刺激的 C 肽水平呈负相关（P<0.05）。研究开始时 TNFα 和 IL-10 的浓度可预测 6 个月时刺激的 C 肽水平（P=0.011 和 P=0.043，分别调整性别、年龄、HbA1c 和青春期阶段）。
在新发 T1D 中，系统细胞因子水平，特别是 TNFα，与残余β细胞功能相关，可能作为疾病缓解和进展的预后生物标志物，以优化治疗策略。
该研究符合赫尔辛基第二宣言的标准，并获得丹麦首都地区生物医学研究伦理委员会（期刊编号 H-3-2014-052）的批准。所有参与者的父母均书面同意。
