Neutrophil Extracellular Traps (NETs) Are Associated with Type 2 Diabetes and Diabetic Foot Ulcer Related Amputation: A Prospective Cohort Study
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 trea...
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| creator | Ibrahim, Irshat Nuermaimaiti, Yilimire Maimaituxun, Gulijianaiti Luo, Xinling Maimaituxun, Mailudemu Akbar, Azimat Tuerxun, Kahaer Wu, Yuanquan |
| description | 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
|
| doi_str_mv | 10.1007/s13300-024-01579-6 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_11096146</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>3055248112</sourcerecordid><originalsourceid>FETCH-LOGICAL-c426t-3bab490b88fd9c2f21ecc1bd5aa17be2cb86179496c885e05e3e13603c7e7ef73</originalsourceid><addsrcrecordid>eNp9UU1v1DAUtBCIVkv_AAdkiUs5BPyRODEXFG23gFQVBNuz5TgvXVfZONhOy_4LfjLe7nYLHPDBfpbnjd_MIPSSkreUkPJdoJwTkhGWZ4QWpczEE3RMK5EKKejTQ13wI3QSwg1Ji0spKX2OjnglqBSSHaNflzBF78aV7fHiZ_TaQN9PvfZ46fUY8OnlYhne4NoDrkNwxuoILb6zcYWXmxEww2dWNxAhYD20-4s1-Ny5iK96Ax5_g_6-qV6PU9TRuuE9rvFX78IIJtpbwHO3cj7i73FqNy_Qs073AU725wxdnS-W80_ZxZePn-f1RWZyJmLGG93kkjRV1bXSsI5RMIY2baE1LRtgpkkSS5lLYaqqAFIAB8oF4aaEErqSz9CHHe84NWtoDQxJfK9Gb9fab5TTVv39MtiVuna3ilKSDM5FYjjdM3j3Y4IQ1dqGrX16ADcFxZPfjIs8bTP0-h_ojZv8kPQlVFGwvKJ0i2I7lEneBA_dYRpK1DZ0tQtdpdDVfehqO8WrP3UcWh4iTgC-A4T0NFyDf_z7P7S_AXcduPQ</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>3055248112</pqid></control><display><type>article</type><title>Neutrophil Extracellular Traps (NETs) Are Associated with Type 2 Diabetes and Diabetic Foot Ulcer Related Amputation: A Prospective Cohort Study</title><source>Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals</source><source>PubMed Central</source><source>Springer Nature OA Free Journals</source><creator>Ibrahim, Irshat ; Nuermaimaiti, Yilimire ; Maimaituxun, Gulijianaiti ; Luo, Xinling ; Maimaituxun, Mailudemu ; Akbar, Azimat ; Tuerxun, Kahaer ; Wu, Yuanquan</creator><creatorcontrib>Ibrahim, Irshat ; Nuermaimaiti, Yilimire ; Maimaituxun, Gulijianaiti ; Luo, Xinling ; Maimaituxun, Mailudemu ; Akbar, Azimat ; Tuerxun, Kahaer ; Wu, Yuanquan</creatorcontrib><description>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.</description><identifier>ISSN: 1869-6953</identifier><identifier>EISSN: 1869-6961</identifier><identifier>DOI: 10.1007/s13300-024-01579-6</identifier><identifier>PMID: 38619692</identifier><language>eng</language><publisher>Cheshire: Springer Healthcare</publisher><subject>Amputation ; Cardiology ; Diabetes ; Endocrinology ; Foot diseases ; Internal Medicine ; Leg ulcers ; Medicine ; Medicine & Public Health ; Neutrophils ; Original Research</subject><ispartof>Diabetes therapy, 2024-06, Vol.15 (6), p.1333-1348</ispartof><rights>The Author(s) 2024</rights><rights>2024. The Author(s).</rights><rights>The Author(s) 2024. This work is published under http://creativecommons.org/licenses/by-nc/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><cites>FETCH-LOGICAL-c426t-3bab490b88fd9c2f21ecc1bd5aa17be2cb86179496c885e05e3e13603c7e7ef73</cites><orcidid>0000-0002-1391-9871</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC11096146/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC11096146/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,881,27901,27902,41096,42165,51551,53766,53768</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/38619692$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Ibrahim, Irshat</creatorcontrib><creatorcontrib>Nuermaimaiti, Yilimire</creatorcontrib><creatorcontrib>Maimaituxun, Gulijianaiti</creatorcontrib><creatorcontrib>Luo, Xinling</creatorcontrib><creatorcontrib>Maimaituxun, Mailudemu</creatorcontrib><creatorcontrib>Akbar, Azimat</creatorcontrib><creatorcontrib>Tuerxun, Kahaer</creatorcontrib><creatorcontrib>Wu, Yuanquan</creatorcontrib><title>Neutrophil Extracellular Traps (NETs) Are Associated with Type 2 Diabetes and Diabetic Foot Ulcer Related Amputation: A Prospective Cohort Study</title><title>Diabetes therapy</title><addtitle>Diabetes Ther</addtitle><addtitle>Diabetes Ther</addtitle><description>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.</description><subject>Amputation</subject><subject>Cardiology</subject><subject>Diabetes</subject><subject>Endocrinology</subject><subject>Foot diseases</subject><subject>Internal Medicine</subject><subject>Leg ulcers</subject><subject>Medicine</subject><subject>Medicine & Public Health</subject><subject>Neutrophils</subject><subject>Original Research</subject><issn>1869-6953</issn><issn>1869-6961</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2024</creationdate><recordtype>article</recordtype><sourceid>C6C</sourceid><sourceid>BENPR</sourceid><recordid>eNp9UU1v1DAUtBCIVkv_AAdkiUs5BPyRODEXFG23gFQVBNuz5TgvXVfZONhOy_4LfjLe7nYLHPDBfpbnjd_MIPSSkreUkPJdoJwTkhGWZ4QWpczEE3RMK5EKKejTQ13wI3QSwg1Ji0spKX2OjnglqBSSHaNflzBF78aV7fHiZ_TaQN9PvfZ46fUY8OnlYhne4NoDrkNwxuoILb6zcYWXmxEww2dWNxAhYD20-4s1-Ny5iK96Ax5_g_6-qV6PU9TRuuE9rvFX78IIJtpbwHO3cj7i73FqNy_Qs073AU725wxdnS-W80_ZxZePn-f1RWZyJmLGG93kkjRV1bXSsI5RMIY2baE1LRtgpkkSS5lLYaqqAFIAB8oF4aaEErqSz9CHHe84NWtoDQxJfK9Gb9fab5TTVv39MtiVuna3ilKSDM5FYjjdM3j3Y4IQ1dqGrX16ADcFxZPfjIs8bTP0-h_ojZv8kPQlVFGwvKJ0i2I7lEneBA_dYRpK1DZ0tQtdpdDVfehqO8WrP3UcWh4iTgC-A4T0NFyDf_z7P7S_AXcduPQ</recordid><startdate>20240601</startdate><enddate>20240601</enddate><creator>Ibrahim, Irshat</creator><creator>Nuermaimaiti, Yilimire</creator><creator>Maimaituxun, Gulijianaiti</creator><creator>Luo, Xinling</creator><creator>Maimaituxun, Mailudemu</creator><creator>Akbar, Azimat</creator><creator>Tuerxun, Kahaer</creator><creator>Wu, Yuanquan</creator><general>Springer Healthcare</general><general>Springer Nature B.V</general><scope>C6C</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7RV</scope><scope>7X7</scope><scope>7XB</scope><scope>8AO</scope><scope>8C1</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>K9-</scope><scope>K9.</scope><scope>KB0</scope><scope>M0R</scope><scope>M0S</scope><scope>NAPCQ</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0002-1391-9871</orcidid></search><sort><creationdate>20240601</creationdate><title>Neutrophil Extracellular Traps (NETs) Are Associated with Type 2 Diabetes and Diabetic Foot Ulcer Related Amputation: A Prospective Cohort Study</title><author>Ibrahim, Irshat ; Nuermaimaiti, Yilimire ; Maimaituxun, Gulijianaiti ; Luo, Xinling ; Maimaituxun, Mailudemu ; Akbar, Azimat ; Tuerxun, Kahaer ; Wu, Yuanquan</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c426t-3bab490b88fd9c2f21ecc1bd5aa17be2cb86179496c885e05e3e13603c7e7ef73</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2024</creationdate><topic>Amputation</topic><topic>Cardiology</topic><topic>Diabetes</topic><topic>Endocrinology</topic><topic>Foot diseases</topic><topic>Internal Medicine</topic><topic>Leg ulcers</topic><topic>Medicine</topic><topic>Medicine & Public Health</topic><topic>Neutrophils</topic><topic>Original Research</topic><toplevel>online_resources</toplevel><creatorcontrib>Ibrahim, Irshat</creatorcontrib><creatorcontrib>Nuermaimaiti, Yilimire</creatorcontrib><creatorcontrib>Maimaituxun, Gulijianaiti</creatorcontrib><creatorcontrib>Luo, Xinling</creatorcontrib><creatorcontrib>Maimaituxun, Mailudemu</creatorcontrib><creatorcontrib>Akbar, Azimat</creatorcontrib><creatorcontrib>Tuerxun, Kahaer</creatorcontrib><creatorcontrib>Wu, Yuanquan</creatorcontrib><collection>Springer Nature OA Free Journals</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Proquest Nursing & Allied Health Source</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>ProQuest Pharma Collection</collection><collection>Public Health Database</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>ProQuest Central</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>Consumer Health Database (Alumni Edition)</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Nursing & Allied Health Database (Alumni Edition)</collection><collection>Consumer Health Database</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Nursing & Allied Health Premium</collection><collection>Publicly Available Content Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Diabetes therapy</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Ibrahim, Irshat</au><au>Nuermaimaiti, Yilimire</au><au>Maimaituxun, Gulijianaiti</au><au>Luo, Xinling</au><au>Maimaituxun, Mailudemu</au><au>Akbar, Azimat</au><au>Tuerxun, Kahaer</au><au>Wu, Yuanquan</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Neutrophil Extracellular Traps (NETs) Are Associated with Type 2 Diabetes and Diabetic Foot Ulcer Related Amputation: A Prospective Cohort Study</atitle><jtitle>Diabetes therapy</jtitle><stitle>Diabetes Ther</stitle><addtitle>Diabetes Ther</addtitle><date>2024-06-01</date><risdate>2024</risdate><volume>15</volume><issue>6</issue><spage>1333</spage><epage>1348</epage><pages>1333-1348</pages><issn>1869-6953</issn><eissn>1869-6961</eissn><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.</abstract><cop>Cheshire</cop><pub>Springer Healthcare</pub><pmid>38619692</pmid><doi>10.1007/s13300-024-01579-6</doi><tpages>16</tpages><orcidid>https://orcid.org/0000-0002-1391-9871</orcidid><oa>free_for_read</oa></addata></record> |
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| source | Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; PubMed Central; Springer Nature OA Free Journals |
| subjects | Amputation Cardiology Diabetes Endocrinology Foot diseases Internal Medicine Leg ulcers Medicine Medicine & Public Health Neutrophils Original Research |
| title | Neutrophil Extracellular Traps (NETs) Are Associated with Type 2 Diabetes and Diabetic Foot Ulcer Related Amputation: A Prospective Cohort Study |
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