Neutrophil Extracellular Traps (NETs) Are Associated with Type 2 Diabetes and Diabetic Foot Ulcer Related Amputation: A Prospective Cohort Study

IF 3.8 3区医学 Q2 Medicine Diabetes Therapy Pub Date : 2024-04-15 DOI:10.1007/s13300-024-01579-6

Irshat Ibrahim, Yilimire Nuermaimaiti, Gulijianaiti Maimaituxun, Xinling Luo, Mailudemu Maimaituxun, Azimat Akbar, Kahaer Tuerxun, Yuanquan Wu

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Abstract

Introduction

The prevalence of diabetes mellitus and its sequelae has been on the rise, and diabetic foot ulcer (DFU) is the leading cause of non-traumatic lower limb amputation globally. The rising occurrence and financial burden associated with DFU necessitate improved clinical assessment and treatment. Diabetes has been found to enhance the formation of neutrophil extracellular traps (NETs) by neutrophils, and excessive NETs have been implicated in tissue damage and impaired wound healing. However, there is as yet insufficient evidence to clarify the value of NETs in assessing and predicting outcomes of DFU.

Methods

We designed this prospective study with three cohorts formed from type 2 diabetes mellitus (T2DM) patients with DFU (n = 200), newly diagnosed T2DM patients (n = 42), and healthy donors (n = 38). Serum levels of NETs were detected for all groups, and the prognostic value for DFU-related amputation was analyzed.

Results

The results showed that serum NET levels of the DFU group were significantly higher than in the T2DM group (P < 0.05), which also had significantly elevated serum NET levels compared to healthy donors (P < 0.05). Multivariate Cox regression showed that serum NET levels, diabetic foot surgical history, and Wagner grade were the risk factors for amputation (P < 0.05), and these three variables also exhibited the highest coefficient values in additional Lasso Cox regression. For patients with DFU, Kaplan-Meier curves showed that high serum NET levels associated with higher amputation probability (HR = 0.19, P < 0.01) and ROC curve based on NET value showed good validity for amputation (AUC: 0.727, CI 0.651–0.803).

Conclusion

Elevated serum NET levels serve as an easily accessible serological prognostic marker for assessing the risk of DFU-related amputation, thereby offering evaluation metrics for healthcare providers. Further investigations are necessary to understand the mechanisms driving this relationship.

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中性粒细胞胞外陷阱（NET）与 2 型糖尿病和糖尿病足溃疡相关截肢有关：一项前瞻性队列研究

导言糖尿病及其后遗症的发病率呈上升趋势，糖尿病足溃疡（DFU）是全球非外伤性下肢截肢的主要原因。糖尿病足溃疡的发生率和经济负担不断增加，因此有必要改进临床评估和治疗。研究发现，糖尿病会促进中性粒细胞形成细胞外捕获物（NET），而过多的NET与组织损伤和伤口愈合受损有关。我们设计了这项前瞻性研究，从患有 DFU 的 2 型糖尿病 (T2DM) 患者（n = 200）、新诊断的 T2DM 患者（n = 42）和健康供体（n = 38）中抽取了三个队列。结果表明，DFU 组的血清 NET 水平明显高于 T2DM 组（P < 0.05），而 T2DM 组的血清 NET 水平也明显高于健康供体（P < 0.05）。多变量 Cox 回归显示，血清 NET 水平、糖尿病足手术史和 Wagner 分级是截肢的危险因素（P < 0.05），这三个变量在附加 Lasso Cox 回归中也显示出最高的系数值。对于 DFU 患者，Kaplan-Meier 曲线显示高血清 NET 水平与较高的截肢概率相关（HR = 0.19，P < 0.01），基于 NET 值的 ROC 曲线显示截肢的有效性良好（AUC：0.727，CI 0.651-0.803）。要了解这种关系的驱动机制，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。

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来源期刊

Diabetes Therapy Medicine-Endocrinology, Diabetes and Metabolism

CiteScore

6.90

自引率

7.90%

发文量

130

审稿时长

6 weeks

期刊介绍： Diabetes Therapy is an international, peer reviewed, rapid-publication (peer review in 2 weeks, published 3–4 weeks from acceptance) journal dedicated to the publication of high-quality clinical (all phases), observational, real-world, and health outcomes research around the discovery, development, and use of therapeutics and interventions (including devices) across all areas of diabetes. Studies relating to diagnostics and diagnosis, pharmacoeconomics, public health, epidemiology, quality of life, and patient care, management, and education are also encouraged. The journal is of interest to a broad audience of healthcare professionals and publishes original research, reviews, communications and letters. The journal is read by a global audience and receives submissions from all over the world. Diabetes Therapy will consider all scientifically sound research be it positive, confirmatory or negative data. Submissions are welcomed whether they relate to an international and/or a country-specific audience, something that is crucially important when researchers are trying to target more specific patient populations. This inclusive approach allows the journal to assist in the dissemination of all scientifically and ethically sound research.