{"title":"Neutrophil Extracellular Traps (NETs) Are Associated with Type 2 Diabetes and Diabetic Foot Ulcer Related Amputation: A Prospective Cohort Study","authors":"Irshat Ibrahim, Yilimire Nuermaimaiti, Gulijianaiti Maimaituxun, Xinling Luo, Mailudemu Maimaituxun, Azimat Akbar, Kahaer Tuerxun, Yuanquan Wu","doi":"10.1007/s13300-024-01579-6","DOIUrl":null,"url":null,"abstract":"<h3 data-test=\"abstract-sub-heading\">Introduction</h3><p>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.</p><h3 data-test=\"abstract-sub-heading\">Methods</h3><p>We designed this prospective study with three cohorts formed from type 2 diabetes mellitus (T2DM) patients with DFU (<i>n</i> = 200), newly diagnosed T2DM patients (<i>n</i> = 42), and healthy donors (<i>n</i> = 38). Serum levels of NETs were detected for all groups, and the prognostic value for DFU-related amputation was analyzed.</p><h3 data-test=\"abstract-sub-heading\">Results</h3><p>The results showed that serum NET levels of the DFU group were significantly higher than in the T2DM group (<i>P</i> < 0.05), which also had significantly elevated serum NET levels compared to healthy donors (<i>P</i> < 0.05). Multivariate Cox regression showed that serum NET levels, diabetic foot surgical history, and Wagner grade were the risk factors for amputation (<i>P</i> < 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, <i>P</i> < 0.01) and ROC curve based on NET value showed good validity for amputation (AUC: 0.727, CI 0.651–0.803).</p><h3 data-test=\"abstract-sub-heading\">Conclusion</h3><p>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.</p>","PeriodicalId":11192,"journal":{"name":"Diabetes Therapy","volume":null,"pages":null},"PeriodicalIF":3.8000,"publicationDate":"2024-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Diabetes Therapy","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1007/s13300-024-01579-6","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"Medicine","Score":null,"Total":0}
引用次数: 0
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.
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.