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横断面研究调查 1 型糖尿病青少年炎症生物标志物与神经病变之间的关系。

Cross-sectional study investigating the association between inflammatory biomarkers and neuropathy in adolescents with type 1 diabetes.

机构信息

Steno Diabetes Center Aarhus, Aarhus University Hospital, Aarhus, Denmark

Danish Pain Research Center, Department of Clinical Medicine, Aarhus University, Aarhus, Denmark.

出版信息

BMJ Open. 2023 Oct 6;13(10):e074992. doi: 10.1136/bmjopen-2023-074992.

Abstract

OBJECTIVES

The aims of this study were to investigate circulating levels of inflammatory markers in adolescents with type 1 diabetes with and without different types of neuropathies and evaluate the association between inflammatory biomarkers, nerve function and clinical parameters.

DESIGN

Cross-sectional study.

SETTING

Hospitals and Steno Diabetes Center in Denmark.

PARTICIPANTS

Adolescents with more than 5 years of diabetes duration were investigated for large fibre, small fibre and autonomic neuropathy as a part of the T1DANES study. Blood samples from the participants were analysed for inflammatory biomarkers by Meso Scale Discovery multiplexing technology.

PRIMARY AND SECONDARY OUTCOME MEASURES

Inflammatory biomarkers and results of diagnostic nerve tests.

RESULTS

Fifty-six adolescents with type 1 diabetes and 23 healthy controls were included. The adolescents with diabetes had significantly higher interferon-gamma, tumour necrosis factor-alpha (TNF-a), interleukin (IL)-10 and soluble urokinase plasminogen activator receptor (suPAR) compared with healthy controls (p values<0.05). TNF-a was higher in the adolescents with large fibre neuropathy (LFN) (p=0.03) compared with those without LFN in the group with diabetes. A negative correlation was seen between TNF-a and conduction velocity in nervus tibialis (p=0.04), and higher TNF-a and IL-6 were associated with higher gastric motility index (TNF-a, p value=0.03; IL-6, p value=0.02). There were no significant associations between inflammatory markers and expressed symptoms, haemoglobin A1c, diabetes duration or body mass index standard derivation score (p values>0.05). The receiver operating characteristic (ROC) curves for the inflammatory markers suggested them as poor screening methods for all types of neuropathies with an area under the curve between 0.47 and 0.67.

CONCLUSION

Our results confirm increased low-grade inflammation in adolescents with type 1 diabetes. TNF-a was higher in adolescents with LFN and correlated negatively with nervus tibialis conduction velocity. The other inflammatory biomarkers fail to support differences in those with and without different types of diabetic neuropathies. However, TNF-a and IL-6 were positively correlated to gastric motility index.

摘要

目的

本研究旨在探讨伴有或不伴有不同类型神经病变的 1 型糖尿病青少年患者循环炎症标志物水平,并评估炎症生物标志物与神经功能和临床参数之间的关系。

设计

横断面研究。

地点

丹麦的医院和 Steno 糖尿病中心。

参与者

作为 T1DANES 研究的一部分,对糖尿病病程超过 5 年的青少年进行大纤维、小纤维和自主神经病变的检测。通过 Meso Scale Discovery 多重分析技术对参与者的血液样本进行炎症生物标志物分析。

主要和次要结果测量

炎症生物标志物和诊断性神经测试结果。

结果

共纳入 56 例 1 型糖尿病青少年和 23 例健康对照者。与健康对照组相比,糖尿病青少年的干扰素-γ、肿瘤坏死因子-α(TNF-α)、白细胞介素(IL)-10 和可溶性尿激酶型纤溶酶原激活物受体(suPAR)显著升高(p 值均<0.05)。与无大纤维神经病变(LFN)的糖尿病青少年相比,伴有 LFN 的青少年 TNF-α水平更高(p=0.03)。在糖尿病青少年中,TNF-α与胫神经传导速度呈负相关(p=0.04),TNF-α和 IL-6 水平与胃动力指数呈正相关(TNF-α,p 值=0.03;IL-6,p 值=0.02)。炎症标志物与症状表达、糖化血红蛋白(HbA1c)、糖尿病病程或体重指数标准差评分均无显著相关性(p 值均>0.05)。炎症标志物的受试者工作特征(ROC)曲线表明,它们作为所有类型神经病变的筛查方法效果不佳,曲线下面积在 0.47 至 0.67 之间。

结论

本研究结果证实 1 型糖尿病青少年存在低度炎症反应增强。伴有 LFN 的青少年 TNF-α水平更高,且与胫神经传导速度呈负相关。其他炎症标志物未能支持伴有或不伴有不同类型糖尿病神经病变的青少年之间存在差异。然而,TNF-α和 IL-6 与胃动力指数呈正相关。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a3cf/10565182/f43065dddf8c/bmjopen-2023-074992f01.jpg

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