Klimontov Vadim V, Mavlianova Kamilla R, Orlov Nikolai B, Semenova Julia F, Korbut Anton I
Laboratory of Endocrinology, Research Institute of Clinical and Experimental Lymphology-Branch of the Institute of Cytology and Genetics, Siberian Branch of Russian Academy of Sciences (RICEL-Branch of IC&G SB RAS), 630060 Novosibirsk, Russia.
Laboratory of Clinical Immunogenetics, Research Institute of Clinical and Experimental Lymphology-Branch of the Institute of Cytology and Genetics, Siberian Branch of Russian Academy of Sciences (RICEL-Branch of IC&G SB RAS), 630060 Novosibirsk, Russia.
Biomedicines. 2023 Oct 19;11(10):2843. doi: 10.3390/biomedicines11102843.
The detrimental effect of hyperglycemia and glucose variability (GV) on target organs in diabetes can be implemented through a wide network of regulatory peptides. In this study, we assessed a broad panel of serum cytokines and growth factors in subjects with type 1 diabetes (T1D) and estimated associations between concentrations of these molecules with time in ranges (TIRs) and GV. One hundred and thirty subjects with T1D and twenty-seven individuals with normal glucose tolerance (control) were included. Serum levels of 44 cytokines and growth factors were measured using a multiplex bead array assay. TIRs and GV parameters were derived from continuous glucose monitoring. Subjects with T1D compared to control demonstrated an increase in concentrations of IL-1β, IL-1Ra, IL-2Rα, IL-3, IL-6, IL-7, IL-12 p40, IL-16, IL-17A, LIF, M-CSF, IFN-α2, IFN-γ, MCP-1, MCP-3, and TNF-α. Patients with TIR ≤ 70% had higher levels of IL-1α, IL-1β, IL-6, IL-12 p70, IL-16, LIF, M-CSF, MCP-1, MCP-3, RANTES, TNF-α, TNF-β, and b-NGF, and lower levels of IL-1α, IL-4, IL-10, GM-CSF, and MIF than those with TIR > 70%. Serum IL-1β, IL-10, IL-12 p70, MCP-1, MCP-3, RANTES, SCF, and TNF-α correlated with TIR and time above range. IL-1β, IL-8, IL-10, IL-12 p70, MCP-1, RANTES, MIF, and SDF-1α were related to at least one amplitude-dependent GV metric. In logistic regression models, IL-1β, IL-4, IL-10, IL-12 p70, GM-CSF, HGF, MCP-3, and TNF-α were associated with TIR ≤ 70%, and MIF and PDGF-BB demonstrated associations with coefficient of variation values ≥ 36%. These results provide further insight into the pathophysiological effects of hyperglycemia and GV in people with diabetes.
高血糖和血糖变异性（GV）对糖尿病靶器官的有害作用可通过广泛的调节肽网络来实现。在本研究中，我们评估了1型糖尿病（T1D）患者的一系列血清细胞因子和生长因子，并估计了这些分子浓度与血糖波动范围（TIRs）和GV之间的关联。纳入了130例T1D患者和27例糖耐量正常的个体（对照组）。使用多重微珠阵列分析法测量44种细胞因子和生长因子的血清水平。TIRs和GV参数来自连续血糖监测。与对照组相比，T1D患者的IL-1β、IL-1Ra、IL-2Rα、IL-3、IL-6、IL-7、IL-12 p40、IL-16、IL-17A、白血病抑制因子（LIF）、巨噬细胞集落刺激因子（M-CSF）、干扰素-α2（IFN-α2）、干扰素-γ（IFN-γ）、单核细胞趋化蛋白-1（MCP-1）、单核细胞趋化蛋白-3（MCP-3）和肿瘤坏死因子-α（TNF-α）浓度升高。TIR≤70%的患者与TIR>70%的患者相比，IL-1α、IL-1β、IL-6、IL-12 p70、IL-16、LIF、M-CSF、MCP-1、MCP-3、调节激活正常T细胞表达和分泌因子（RANTES）、TNF-α、TNF-β和脑源性神经营养因子（b-NGF）水平较高，而IL-1α、IL-4、IL-10、粒细胞-巨噬细胞集落刺激因子（GM-CSF）和巨噬细胞移动抑制因子（MIF）水平较低。血清IL-1β、IL-10、IL-12 p70、MCP-1、MCP-3、RANTES、干细胞因子（SCF）和TNF-α与TIR及高于范围的时间相关。IL-1β、IL-8、IL-10、IL-12 p70、MCP-1、RANTES、MIF和基质细胞衍生因子-1α（SDF-1α）与至少一种幅度依赖性GV指标相关。在逻辑回归模型中，IL-1β、IL-4、IL-10、IL-12 p70、GM-CSF、肝细胞生长因子（HGF）、MCP-3和TNF-α与TIR≤70%相关，而MIF和血小板衍生生长因子-BB（PDGF-BB）与变异系数值≥36%相关。这些结果为深入了解高血糖和GV在糖尿病患者中的病理生理作用提供了进一步的依据。
