Department of Paediatrics, Hospital for Sick Children, University of Toronto, Toronto, Canada; Division of Endocrinology, Hospital for Sick Children, Toronto, Canada.
Department of Paediatrics, Hospital for Sick Children, University of Toronto, Toronto, Canada; Division of Nephrology, Hospital for Sick Children, Toronto, Canada.
Cytokine. 2017 Nov;99:233-239. doi: 10.1016/j.cyto.2017.07.013. Epub 2017 Jul 29.
The contribution of inflammation to endothelial/vascular dysfunction in early Type I Diabetes (T1D) is not well understood. The objective of this study was to examine the interaction between systemic inflammation and vascular function in adolescent's with and without-T1D.
51 subjects from our observational cohort of adolescents with T1D (JDRF-CCTN), and 59 healthy controls (HC) were studied. Serum cytokines-chemokines were quantified using Human 41-Plex Array, and vascular function was measured by Flow Mediated Dilatation (FMD), Pulse Wave Velocity (PWV) and Blood Pressure (BP). Factor Analysis was used to identify pro- and anti-inflammatory cytokine-chemokine factors, which were then correlated with vascular outcomes.
Three pro-inflammatory factors were identified in HC and three in TID, and a single anti-inflammatory factor in both groups. In HC there was a positive correlation (r=0.33; p=0.01) between control proinflammatory Factor 1 and systolic BP and a negative correlation between control proinflammatory Factor 3(r=-0.29; p=0.02) and diastolic BP. Control proinflammatory Factor 2 correlated positively with PWV. In TID subjects, no correlations were found between any of the pro-inflammatory factors and the vascular measurements. No correlations were found between the anti-inflammatory factors and BP, FMD and PWV in either HC or T1D. Levels of pro-inflammatory analytes, EGF, GRO, PDGF-BB, PDGF-AA and sCD40L were significantly higher in T1D.
The cytokine-chemokine signature in early T1D, prior to the development of arterial disease, is significantly different from that seen in healthy controls. This may be relevant to pathophysiology, determining risk and identifying target cytokines-chemokines for intervention in T1D.
炎症对 1 型糖尿病(T1D)早期内皮/血管功能障碍的影响尚不清楚。本研究旨在探讨青少年 T1D 患者和非 T1D 患者中系统性炎症与血管功能之间的相互作用。
本研究纳入了来自我们青少年 1 型糖尿病观察队列(JDRF-CCTN)的 51 名 T1D 患者和 59 名健康对照者(HC)。使用 Human 41-Plex Array 定量检测血清细胞因子-趋化因子,通过血流介导的扩张(FMD)、脉搏波速度(PWV)和血压(BP)测量血管功能。采用因子分析识别促炎和抗炎细胞因子-趋化因子因子,并与血管结局进行相关性分析。
在 HC 中鉴定出 3 个促炎因子,在 TID 中鉴定出 3 个促炎因子,在两组中均鉴定出 1 个抗炎因子。在 HC 中,对照性促炎因子 1 与收缩压呈正相关(r=0.33;p=0.01),对照性促炎因子 3 与舒张压呈负相关(r=-0.29;p=0.02)。对照性促炎因子 2 与 PWV 呈正相关。在 TID 患者中,任何促炎因子与血管测量均无相关性。在 HC 或 T1D 中,抗炎因子与 BP、FMD 和 PWV 之间均无相关性。T1D 患者中促炎分析物 EGF、GRO、PDGF-BB、PDGF-AA 和 sCD40L 的水平显著升高。
在动脉疾病发生之前,T1D 早期的细胞因子-趋化因子特征与健康对照者明显不同。这可能与病理生理学有关,有助于确定风险,并确定 T1D 干预的目标细胞因子-趋化因子。