促炎细胞因子与 1 型糖尿病青少年动脉僵化之间的关系

Mónica Reis, Ana Teixeira, Juliana Cardoso, Teresa Borges, Alberto Caldas Afonso, Liane Correia-Costa
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Methods Twenty-three type 1 diabetic patients, aged 12–16 years, followed at a tertiary center, and 23 adolescents nonoverweighted healthy controls, from a Portuguese birth-cohort, were included in the present analysis. Anthropometry, blood pressure, glycemic control data, and lipid parameters were collected. Arterial stiffness was evaluated by carotid–femoral pulse wave velocity. Proinflammatory cytokines’ concentrations (TNF-α, IL-1β, IL-6, IL-10, IFN-γ, and GM-CSF) were quantified by multiplex immunoassays using a Luminex 200 analyzer. Results There were no statistically significant differences between the proinflammatory cytokines’ concentrations in the two groups. PWV [6.63 (6.23–7.07) vs. 6.07 (5.15–6.65) m/s, p=0.015] was significantly higher in the diabetic group. PWV was negatively correlated with GM-CSF (ρ=−0.437, p=0.037) in the diabetic group. A linear association was found between diabetes duration and PWV (with PWV increasing by 0.094 m/s (95 % confidence interval, 0.019 to 0.169) per month of disease duration). In the diabetic group, HbA<jats:sub>1c</jats:sub> was negatively correlated with IL-10 (ρ=−0.473, p=0.026). Negative correlations were also found between IL-10 and total, HDL, and LDL cholesterol only in the diabetic group. Conclusions Diabetic adolescent patients present higher PWV, when compared to their healthy counterparts, even though we could not find differences in the levels of several proinflammatory cytokines between the two groups. The negative correlation found between IL-10 and HbA<jats:sub>1c</jats:sub> might translate a protective counterbalance effect of this anti-inflammatory cytokine, which might also explain the negative correlations found with blood lipids. 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引用次数: 0

摘要

目的 1 型糖尿病被认为是一种慢性低度炎症和先天性免疫系统激活状态,这种状态受多种促炎细胞因子和其他急性期反应物的调节。动脉僵化是通过测定脉搏波速度(PWV)来评估血管动态特性的一种方法,糖尿病患者的动脉僵化会增加,并与糖尿病的微血管和大血管并发症以及较高的心血管风险有关。在本研究中,我们旨在比较糖尿病青少年和非糖尿病青少年的前炎症状态和动脉僵化,并描述这两个参数之间的关联。方法 23 名年龄在 12-16 岁的 1 型糖尿病患者在一家三级医疗中心接受随访,23 名青少年非超重健康对照者来自葡萄牙出生队列,均纳入本分析。研究人员收集了人体测量、血压、血糖控制数据和血脂参数。动脉僵化通过颈动脉-股动脉脉搏波速度进行评估。前炎症细胞因子(TNF-α、IL-1β、IL-6、IL-10、IFN-γ 和 GM-CSF)的浓度通过使用 Luminex 200 分析仪的多重免疫测定法进行量化。结果 两组的促炎细胞因子浓度差异无统计学意义。糖尿病组的脉搏波速度[6.63 (6.23-7.07) vs. 6.07 (5.15-6.65) m/s,p=0.015]明显高于对照组。糖尿病组的脉搏波速度与 GM-CSF 呈负相关(ρ=-0.437,p=0.037)。糖尿病病程与脉搏波速度之间呈线性关系(病程每延长一个月,脉搏波速度增加 0.094 米/秒(95% 置信区间为 0.019 至 0.169))。在糖尿病组中,HbA1c 与 IL-10 呈负相关(ρ=-0.473,p=0.026)。仅在糖尿病组中,IL-10 与总胆固醇、高密度脂蛋白胆固醇和低密度脂蛋白胆固醇之间也呈负相关。结论 青少年糖尿病患者的脉搏波速度比健康人高,尽管我们没有发现两组患者的几种促炎细胞因子水平存在差异。IL-10与HbA1c之间的负相关可能是这种抗炎细胞因子的保护性平衡作用,这也可能解释了与血脂之间的负相关。要更好地阐明动脉僵化与糖尿病促炎环境之间的关系,还需要进一步的研究。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Association between proinflammatory cytokines and arterial stiffness in type 1 diabetic adolescents
Objectives Type 1 diabetes mellitus is considered a state of chronic low-grade inflammation and activation of the innate immune system, which is regulated by several proinflammatory cytokines and other acute-phase reactants. Arterial stiffness, a dynamic property of the vessels evaluated by the determination of pulse wave velocity (PWV), is increased in diabetic patients and is associated with microvascular and macrovascular complications of diabetes and higher cardiovascular risk. In the present study, we aimed to compare the proinflammatory state and arterial stiffness in diabetic and non-diabetic adolescents, and to characterize the association between these two parameters. Methods Twenty-three type 1 diabetic patients, aged 12–16 years, followed at a tertiary center, and 23 adolescents nonoverweighted healthy controls, from a Portuguese birth-cohort, were included in the present analysis. Anthropometry, blood pressure, glycemic control data, and lipid parameters were collected. Arterial stiffness was evaluated by carotid–femoral pulse wave velocity. Proinflammatory cytokines’ concentrations (TNF-α, IL-1β, IL-6, IL-10, IFN-γ, and GM-CSF) were quantified by multiplex immunoassays using a Luminex 200 analyzer. Results There were no statistically significant differences between the proinflammatory cytokines’ concentrations in the two groups. PWV [6.63 (6.23–7.07) vs. 6.07 (5.15–6.65) m/s, p=0.015] was significantly higher in the diabetic group. PWV was negatively correlated with GM-CSF (ρ=−0.437, p=0.037) in the diabetic group. A linear association was found between diabetes duration and PWV (with PWV increasing by 0.094 m/s (95 % confidence interval, 0.019 to 0.169) per month of disease duration). In the diabetic group, HbA1c was negatively correlated with IL-10 (ρ=−0.473, p=0.026). Negative correlations were also found between IL-10 and total, HDL, and LDL cholesterol only in the diabetic group. Conclusions Diabetic adolescent patients present higher PWV, when compared to their healthy counterparts, even though we could not find differences in the levels of several proinflammatory cytokines between the two groups. The negative correlation found between IL-10 and HbA1c might translate a protective counterbalance effect of this anti-inflammatory cytokine, which might also explain the negative correlations found with blood lipids. Further studies are needed to better clarify the association between arterial stiffness and the proinflammatory milieu of diabetes.
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