Introduction. A neuroimmune communication exists, and compelling evidence suggests that diabetic neuropathy and systemic inflammation are linked. Our aims were (1) to investigate biomarkers of the ongoing inflammation processes including cytokines, adhesion molecules, and chemokines and (2) to associate the findings with cardiovascular autonomic neuropathy in type 1 diabetes by measuring heart rate variability and cardiac vagal tone. Materials and Methods. We included 104 adults with type 1 diabetes. Heart rate variability, time domain, and frequency domains were calculated from a 24-hour Holter electrocardiogram, while cardiac vagal tone was determined from a 5-minute electrocardiogram. Cytokines (interleukin- (IL-) 1α, IL-4, IL-12p70, IL-13, IL-17, and tumor necrosis factor- (TNF-) α), adhesion molecules (E-selectin, P-selectin, and intercellular adhesion molecule- (ICAM-) 1), and chemokines (chemokine (C-C motif) ligand (CCL)2, CCL3, CCL4, and C-X-C motif chemokine (CXCL)10) were assessed using a Luminex multiplexing technology. Associations between concentrations of inflammatory biomarkers and continuous variables of heart rate variability and cardiac vagal tone were estimated using multivariable linear regression adjusting for age, sex, disease duration, and smoking. Results. Participants with the presence of cardiovascular autonomic neuropathy had higher systemic levels of IL-1α, IL-4, CCL2, and E-selectin than those without cardiovascular autonomic neuropathy. IL-1α, IL-4, IL-12, TNF-α, and E-selectin were inversely associated with both sympathetic and parasympathetic heart rate variability measures (). Discussion. Our results show that several pro- and anti-inflammatory factors, believed to be involved in the progression of diabetic polyneuropathy, are associated with cardiovascular autonomic neuropathy, suggesting that these factors may also contribute to the pathogenesis of cardiovascular autonomic neuropathy. Our findings emphasize the importance of the neuroimmune regulatory system in the pathogenesis of neuropathy in type 1 diabetes.

中文翻译：

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循环炎症标志物与 1 型糖尿病的心率变异性测量呈负相关。

简介。存在神经免疫沟通，令人信服的证据表明糖尿病性神经病变和全身炎症相关。我们的目标是 (1) 研究正在进行的炎症过程的生物标志物，包括细胞因子、粘附分子和趋化因子，以及 (2) 通过测量心率变异性和心脏迷走神经张力将这些发现与 1 型糖尿病的心血管自主神经病变相关联。材料和方法。我们纳入了 104 名患有 1 型糖尿病的成年人。心率变异性、时域和频域由 24 小时动态心电图计算得出，而心脏迷走神经张力由 5 分钟心电图确定。细胞因子（白细胞介素- (IL-) 1 α、IL-4、IL-12p70、IL-13、IL-17 和肿瘤坏死因子-（TNF-）α）、粘附分子（E-选择素、P-选择素和细胞间粘附分子-（ICAM-）1 ) 和趋化因子（趋化因子（CC 基序）配体 (CCL)2、CCL3、CCL4 和 CXC 基序趋化因子 (CXCL)10）使用 Luminex 多路复用技术进行评估。炎症生物标志物浓度与心率变异性和心脏迷走神经张力的连续变量之间的关联使用针对年龄、性别、疾病持续时间和吸烟进行调整的多变量线性回归进行估计。结果。存在心血管自主神经病变的参与者比没有心血管自主神经病变的参与者具有更高的全身 IL- 1α、IL-4、CCL2 和 E-选择素水平。IL-1α、IL-4、IL-12、TNF- α和 E-选择素与交感神经和副交感神经心率变异性测量呈负相关（）。 讨论。我们的研究结果表明，一些被认为与糖尿病性多发性神经病进展有关的促炎和抗炎因子与心血管自主神经病变有关，这表明这些因素也可能有助于心血管自主神经病变的发病机制。我们的研究结果强调了神经免疫调节系统在 1 型糖尿病神经病变发病机制中的重要性。